G2Cdb::Gene report

Gene id
Gene symbol
Homo sapiens
enolase 2 (gamma, neuronal)
G00000404 (Mus musculus)

Databases (8)

ENSG00000111674 (Ensembl human gene)
2026 (Entrez Gene)
745 (G2Cdb plasticity & disease)
ENO2 (GeneCards)
131360 (OMIM)
Marker Symbol
HGNC:3353 (HGNC)
Protein Expression
63 (human protein atlas)
Protein Sequence
P09104 (UniProt)

Literature (44)

Pubmed - other

  • Proliferation and multi-differentiation potentials of human mesenchymal stem cells on thermoresponsive PDMS surfaces grafted with PNIPAAm.

    Shi D, Ma D, Dong F, Zong C, Liu L, Shen D, Yuan W, Tong X, Chen H and Wang J

    The Institute of Cell Biology and Genetics, College of Biological Sciences, Zhejiang University, Zijingang Campus, Hangzhou, Zhejiang 310058, China.

    The thermo-responsivity of PNIPAAm [poly(N-isopropylcarylamide)]-grafted PDMS [poly(dimethylsiloxane)] surface is a property that could be feasibly used for detaching cells adhered on the surface. We used benzophenone-initiated photopolymerization to graft PNIPAAm on PDMS substrates to construct the PNIPAAm-grafted PDMS surface and this PDMS surface was highly thermo-responsive. hMSCs (human mesenchymal stem cells) were used to analyse the proliferation and multi-differentiation of stem cells on the PNIPAAm-grafted PDMS surface. The results showed that hMSCs could adhere on the PNIPAAm-grafted PDMS surface at 37 degrees C and form cell colonies, and then become fibroblastic. The proliferation potential of hMSCs on the PNIPAAm-grafted PDMS surface was not significantly different from that on a plate surface coated with gelatin. However, as it proved easier to detach cells from the surface, by changing temperature, a higher viability of detached cells could be obtained with the PNIPAAm-grafted PDMS surface, using a temperature shift, compared with a gelatin-coated surface, where cells are detached by treatment with trypsin. hMSCs on the PNIPAAm-grafted PDMS surface were induced into osteoblasts, adipocytes and neurocytes under osteogenic medium, adipogenic medium and neurogenic medium respectively. The PNIPAAm-grafted PDMS surface was favourable for osteogenesis of hMSCs, although the potentials of adipogenesis and neurogenesis of hMSCs on the PNIPAAm-grafted PDMS surface were similar to those on the plate surface coated with gelatin. The above results demonstrate that the PNIPAAm-grafted PDMS surface not only kept the potentials of proliferation and multi-differentiation of hMSCs, but also increased the viability of hMSCs.

    Bioscience reports 2009;30;3;149-58

  • Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease.

    Chapuis J, Hot D, Hansmannel F, Kerdraon O, Ferreira S, Hubans C, Maurage CA, Huot L, Bensemain F, Laumet G, Ayral AM, Fievet N, Hauw JJ, DeKosky ST, Lemoine Y, Iwatsubo T, Wavrant-Devrièze F, Dartigues JF, Tzourio C, Buée L, Pasquier F, Berr C, Mann D, Lendon C, Alpérovitch A, Kamboh MI, Amouyel P and Lambert JC

    INSERM, U744, Université de Lille 2, Institut Pasteur de Lille, BP 245,1, rue du professeur Calmette, Lille cedex, France.

    The only recognized genetic determinant of the common forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). To identify new candidate genes, we recently performed transcriptomic analysis of 2741 genes in chromosomal regions of interest using brain tissue of AD cases and controls. From 82 differentially expressed genes, 1156 polymorphisms were genotyped in two independent discovery subsamples (n=945). Seventeen genes exhibited at least one polymorphism associated with AD risk, and following correction for multiple testing, we retained the interleukin (IL)-33 gene. We first confirmed that the IL-33 expression was decreased in the brain of AD cases compared with that of controls. Further genetic analysis led us to select three polymorphisms within this gene, which we analyzed in three independent case-control studies. These polymorphisms and a resulting protective haplotype were systematically associated with AD risk in non-APOE epsilon 4 carriers. Using a large prospective study, these associations were also detected when analyzing the prevalent and incident AD cases together or the incident AD cases alone. These polymorphisms were also associated with less cerebral amyloid angiopathy (CAA) in the brain of non-APOE epsilon 4 AD cases. Immunohistochemistry experiments finally indicated that the IL-33 expression was consistently restricted to vascular capillaries in the brain. Moreover, IL-33 overexpression in cellular models led to a specific decrease in secretion of the A beta(40) peptides, the main CAA component. In conclusion, our data suggest that genetic variants in IL-33 gene may be associated with a decrease in AD risk potentially in modulating CAA formation.

    Funded by: NIA NIH HHS: AG05133, AG13672, P50 AG005133, P50 AG005133-219007, R01 AG013672, R01 AG013672-08

    Molecular psychiatry 2009;14;11;1004-16

  • Jugular venous neurone specific enolase (NSE) increases following carotid endarterectomy under general, but not local, anaesthesia.

    Wijeyaratne SM, Collins MA, Barth JH and Gough MJ

    Leeds Vascular Institute, The General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, UK.

    Introduction: Previous studies indicate that local (LA) rather than general anaesthesia (GA) for carotid endarterectomy (CEA) is associated with reflex hypertension and preservation of cerebral cytochrome oxidase after carotid clamping. The hypothesis that LA offers protection against ischaemic cerebral injury has been investigated by measuring ipsilateral jugular venous neurone specific enolase (NSE: neuronal glycolytic enzyme) and S-100B (glial cell protein) during and after CEA.

    Methods: 27 patients with symptomatic carotid artery disease (70-99% stenosis) underwent CEA, 14 under LA and 13 under GA. Jugular venous blood samples were assayed for NSE and S-100B before carotid clamping and at 5min before and 5min, 2, 4, 6, 8, 12 and 24h after clamp release.

    Results: No neurological complications occurred. S-100B levels were low and did not increase from baseline in either group. Pre-clamp NSE levels were similar in both groups (LA: 17.6 (15.2-20.7)microg/l, GA: 21.5 (11.3-26.2)microg/l; p=0.37) but increased significantly 2h after clamp release in GA patients (LA: 25.5 (16.6-27.8)microg/l, GA: 48.2 (31.4-61.3)microg/l, p=0.05) with a significant rise from baseline in GA patients (p=0.04).

    Conclusions: CEA performed under GA is associated with greater rises in jugular venous NSE, and hence cerebral injury, than CEA performed under LA.

    European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery 2009;38;3;262-6

  • Neuron-specific enolase and S-100B are associated with neurologic outcome after pediatric cardiac arrest.

    Topjian AA, Lin R, Morris MC, Ichord R, Drott H, Bayer CR, Helfaer MA and Nadkarni V

    Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. topjian@email.chop.edu

    Objective: To characterize the pattern of serum biochemical markers of central nervous system injury (neuron-specific enolase [NSE], S-100B, plasminogen activator inhibitor-1 [PAI-1]) after pediatric cardiac arrest and determine whether there is an association between biomarker concentrations and neurologic outcome.

    Design: Prospective, observational study.

    Setting: Urban, tertiary care children's hospital.

    Patients: Cardiac arrest survivors, n = 35.

    Interventions: Serial blood sampling, pediatric cerebral performance category, and standardized neurologic examination.

    Serial serum NSE and S-100B concentrations over 96 hrs and PAI-1 at 24 hrs were measured in children (age <18 yrs) who had return of spontaneous circulation following cardiac arrest. Neurologic outcome was prospectively categorized as poor if the change in pre- to postarrest pediatric cerebral performance category was > or =2. Biomarker concentrations were compared between outcome groups and between survival groups using longitudinal analysis correcting for multiple comparisons. Median levels (25th, 75th percentiles) are reported. Receiver operating characteristic analyses were performed at all time points. Biomarker concentrations showed statistically significant differences. Of the 35 patients, neurologic outcomes were poor in 19, with 15 deaths. Median NSE concentrations differed by outcome when measured at > or =48 hrs, and by survival at > or =24 hrs. S-100B concentrations were not significantly associated with neurologic outcome. S-100B levels were associated with survival outcome at > or =48 hrs. PAI-1 levels were not significantly associated with either neurologic or survival outcomes.

    Conclusions: The timing, intensity, and duration of serum NSE and S-100B biomarker concentration patterns are associated with neurologic and survival outcomes following pediatric cardiac arrest. Serum NSE concentrations at > or =48 hrs are associated with neurologic outcome, whereas serum S-100B levels at > or =48 hrs are associated with survival. Prospective analysis of these markers may help to predict outcomes and guide postresuscitative therapies.

    Funded by: NCRR NIH HHS: MO1-RR00240

    Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 2009;10;4;479-90

  • Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation.

    Martins-de-Souza D, Gattaz WF, Schmitt A, Novello JC, Marangoni S, Turck CW and Dias-Neto E

    Laboratório de Neurociências, Instituto de Psiquiatria, Faculdade de Medicina da USP, Rua Dr, Ovídio Pires de Campos, no 785, São Paulo, SP, CEP 05403-010, Brazil. martins@mpipsykl.mpg.de

    Background: Schizophrenia is likely to be a consequence of DNA alterations that, together with environmental factors, will lead to protein expression differences and the ultimate establishment of the illness. The superior temporal gyrus is implicated in schizophrenia and executes functions such as the processing of speech, language skills and sound processing.

    Methods: We performed an individual comparative proteome analysis using two-dimensional gel electrophoresis of 9 schizophrenia and 6 healthy control patients' left posterior superior temporal gyrus (Wernicke's area - BA22p) identifying by mass spectrometry several protein expression alterations that could be related to the disease.

    Results: Our analysis revealed 11 downregulated and 14 upregulated proteins, most of them related to energy metabolism. Whereas many of the identified proteins have been previously implicated in schizophrenia, such as fructose-bisphosphate aldolase C, creatine kinase and neuron-specific enolase, new putative disease markers were also identified such as dihydrolipoyl dehydrogenase, tropomyosin 3, breast cancer metastasis-suppressor 1, heterogeneous nuclear ribonucleoproteins C1/C2 and phosphate carrier protein, mitochondrial precursor. Besides, the differential expression of peroxiredoxin 6 (PRDX6) and glial fibrillary acidic protein (GFAP) were confirmed by western blot in schizophrenia prefrontal cortex.

    Conclusion: Our data supports a dysregulation of energy metabolism in schizophrenia as well as suggests new markers that may contribute to a better understanding of this complex disease.

    BMC psychiatry 2009;9;17

  • NGF, DCX, and NSE upregulation correlates with severity and outcome of head trauma in children.

    Chiaretti A, Barone G, Riccardi R, Antonelli A, Pezzotti P, Genovese O, Tortorolo L and Conti G

    Terapia Intensiva Pediatrica, Policlinico Gemelli, Largo Gemelli, 1-00168 Rome, Italy. achiaretti@yahoo.it

    Background: Secondary brain damage after traumatic brain injury (TBI) involves neuroinflammatory mechanisms, mainly dependent on the intracerebral production of specific biomarkers, such as cytokines, neurotrophic factors, and neuron-specific enolase (NSE). NSE is associated with neuronal damage, while neurotrophic factors play a neuroprotective role due to their ability to modulate neuronal precursor biosynthesis, such as doublecortin (DCX). However, the relationships between the expression of these factors and the severity and outcome of TBI are not understood.

    Methods: To determine whether the concentrations of neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF]), DCX, and NSE in the CSF of children with TBI correlate with the severity of brain damage and neurologic outcome, we prospectively collected CSF samples from 32 children at 2 and 48 hours after admission for severe TBI and from 32 matched controls. Severity of TBI was evaluated by Glasgow Coma Scale and neurologic outcome by Glasgow Outcome Score.

    Results: Early NGF, DCX, and NSE concentrations correlated significantly with the severity of head injury, whereas no correlation was found for BDNF and GDNF. Furthermore, NGF and DCX upregulation and lower NSE expression were associated with better neurologic outcomes. No significant association was found between BDNF and GDNF expression and outcome.

    Conclusions: Nerve growth factor (NGF), doublecortin (DCX), and neuron-specific enolase concentrations in the CSF are useful markers of brain damage following severe traumatic brain injury (TBI). NGF and DCX upregulation correlates also with better neurologic outcome and could be useful to obtain clinical and prognostic information in children with severe TBI.

    Neurology 2009;72;7;609-16

  • Serum concentrations of s100b and NSE in migraine.

    Teepker M, Munk K, Mylius V, Haag A, Möller JC, Oertel WH and Schepelmann K

    Department of Neurology, Philipps-University, Marburg, Germany.

    Background: The protein s100b indicates astrocytal damage as well as dysfunction of the blood-brain barrier (BBB), and neuron-specific enolase (NSE) is regarded as a marker for neuronal cell loss. Recently, s100b was shown to be a potentially useful marker for migraine in children. In this study, we investigated the levels of s100b and NSE in adult migraineurs during and after migraine attacks in order to gain some more insight into migraine pathophysiology.

    Methods: Serum levels of s100b and NSE were measured in 21 migraineurs and compared with 21 healthy subjects matched by sex and age. In migraineurs, blood samples were taken during a migraine attack and following a pain-free period of 2-4 days.

    Results: During migraine attacks elevated s100b levels could be observed. Maximal concentrations were detected in the pain-free period after 2-4 days. Regarding NSE, serum levels were decreased slightly during and after migraine bouts.

    Conclusions: Our data suggest a prolonged disruption of BBB during and after migraine attacks. Other possible explanations concerning the detected serum levels of s100b and NSE will be discussed; however, neuronal cell death can be ruled out by the decreased serum concentrations of NSE. With regard to the results of the present study, further research is necessary to evaluate the role of s100b and NSE in migraine.

    Headache 2009;49;2;245-52

  • Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation.

    Undén J, Strandberg K, Malm J, Campbell E, Rosengren L, Stenflo J, Norrving B, Romner B, Lindgren A and Andsberg G

    Dept. of Anaesthesiology and Intensive Care, Halmstad Regional Hospital, 30185 Halmstad, Sweden. johan.unden@lthalland.se

    Introduction: A simple and accurate method of differentiating ischemic stroke and intracerebral hemorrhage (ICH) is potentially useful to facilitate acute therapeutic management. Blood measurements of biomarkers of brain damage and activation of the coagulation system may potentially serve as novel diagnostic tools for stroke subtypes.

    Methods: Ninety-seven stroke patients were prospectively investigated in a multicenter design with blood levels of brain biomarkers S100B, neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) as well as a coagulation biomarker, activated protein C-protein C inhibitor complex (APC-PCI), within 24 hours of symptom onset.

    Results: Eighty-three patients (86%) had ischemic stroke and fourteen patients (14%) had ICH. There were no differences in S100B (p=0.13) and NSE (p=0.67) levels between patients with ischemic stroke or ICH. However, GFAP levels were significantly higher in ICH patients (p=0.0057). APC-PCI levels were higher in larger ischemic strokes (p=0.020). The combination of GFAP and APC-PCI levels, in patients with NIHSS score more than 3, had a sensitivity and negative predictive value of 100% for ICH in our material (p=0.0052).

    Conclusion: This exploratory study indicated that blood levels of biomarkers GFAP and APC-PCI, prior to neuroimaging, may rule out ICH in a mixed stroke population.

    Journal of neurology 2009;256;1;72-7

  • Genetic variants in apoptosis and immunoregulation-related genes are associated with risk of chronic lymphocytic leukemia.

    Enjuanes A, Benavente Y, Bosch F, Martín-Guerrero I, Colomer D, Pérez-Alvarez S, Reina O, Ardanaz MT, Jares P, García-Orad A, Pujana MA, Montserrat E, de Sanjosé S and Campo E

    Department of Anatomic Pathology, Hematopathology Section, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.

    To identify low-penetrance susceptibility alleles for chronic lymphocytic leukemia (CLL), we performed a case-control study genotyping 768 single-nucleotide polymorphisms (SNP) in 692 cases of CLL and 738 controls. We investigated nonsynonymous SNPs, SNPs with potential functional effect, and tag SNPs in regulatory gene regions in a total of 172 genes involved in cancer biology. After adjustment for multiple testing, we found a strong association between CLL risk and six genetic variants: CCNH (rs2266690, V270A), APAF1 (rs17028658, 3'region), IL16 (rs4505265, first intron), CASP8 (rs1045485, D302H), NOS2A (rs2779251, promoter), and CCR7 (rs3136687, intron 1). We found association with CLL susceptibility and 22 haplotypes in APAF1, IL6, TNFRSF13B, IL16, CASP3, CCR7, LTA/TNF, BAX, BCL2, CXCL12, CASP10/CASP8, CASP1, CCL2, BAK1, and IL1A candidate genes. Finally, we evaluated using public data sets the potential functional effect on gene expression levels of the CLL associated genetic variants detected in regulatory regions. Minor alleles for APAF1 and IL16 were associated with lower mRNA levels; no expression differences were observed for CCR7, whereas NOS2A could not be assessed. This study suggests that common genetic variation in apoptosis- and immunoregulation-related genes is associated with the CLL risk.

    Cancer research 2008;68;24;10178-86

  • The estrogen hypothesis of schizophrenia implicates glucose metabolism: association study in three independent samples.

    Olsen L, Hansen T, Jakobsen KD, Djurovic S, Melle I, Agartz I, Hall H, Ullum H, Timm S, Wang AG, Jönsson EG, Andreassen OA and Werge T

    Research Institute of Biological Psychiatry, Sct, Hans Hospital, DK-4000 Roskilde, Denmark. line.olsen@shh.regionh.dk

    Background: Schizophrenia is a highly heritable complex psychiatric disorder with an underlying pathophysiology that is still not well understood. Metaanalyses of schizophrenia linkage studies indicate numerous but rather large disease-associated genomic regions, whereas accumulating gene- and protein expression studies have indicated an equally large set of candidate genes that only partially overlap linkage genes. A thorough assessment, beyond the resolution of current GWA studies, of the disease risk conferred by the numerous schizophrenia candidate genes is a daunting and presently not feasible task. We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling networks implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated with schizophrenia or at least with gender-associated aspects of the illness.

    Results: We genotyped 185 SNPs in three independent case-control samples of Scandinavian origin (a total of 765 patients and 1274 control subjects). Variants of the mitogen-activated protein kinase 14 gene (MAPK14) and the phosphoenolpyruvate carboxykinase 1 (PCK1) and fructose-1,6-biphosphatase (FBP1) were nominal significantly associated with schizophrenia, and several haplotypes within enolase 2 gene (ENO2) consist of the same SNP allele having elevated risk of schizophrenia. Importantly, we find no evidence of stratification due to nationality or gender.

    Conclusion: Several gene variants in the Glycolysis were associated with schizophrenia in three independent samples. However, the findings are weak and not resistant to correction for multiple testing, which may indicate that they are either spurious or may relate to a particular subtype or aspect of the illness.

    BMC medical genetics 2008;9;39

  • Reference intervals for carcinoembryonic antigen (CEA), CA125, MUC1, Alfa-foeto-protein (AFP), neuron-specific enolase (NSE) and CA19.9 from the NORIP study.

    Bjerner J, Høgetveit A, Wold Akselberg K, Vangsnes K, Paus E, Bjøro T, Børmer OP and Nustad K

    Central Laboratory, Norwegian Radium Hospital, Montebello, Oslo, Norway. johan.bjerner@medisin.uio.no

    Objective: Adhering to current IFCC recommendations, we calculated upper 97.5 % reference limits for serum tumor markers.

    Serum samples from 498 healthy individuals from the Nordic reference interval project (NORIP) were investigated for carcinoembryonic antigen (CEA), CA125 and MUC1 (episialin, CA15.3) using in-house immunofluorometric assays and, for alpha-foetoprotein (AFP), a PerkinElmer Life Sciences assay, neuron-specific enolase (NSE) using an in-house immunoradiometric assay and CA19.9 using a Beckman Access assay. All assays participate in external quality assessment programs.

    Results: CEA concentrations increased with age and smoking. Upper reference limits for non-smokers were 3.59 microg/L at 50 years and 4.12 microg/L at 70 years. CA125 concentrations were age-independent and the upper reference limit was 35.8 kU/L. MUC1 increased with age and body mass index (BMI). Upper reference limits were 31.7 kU/L at 40 years and BMI 24, 37.5 kU/L at 70 years and BMI 24, and 33.7 kU/L at 40 years and BMI 30. AFP increases with age, and the upper reference limits were 3.82 kU/L at 20 years and 8.70 kU/L at 60 years. An upper reference limit for NSE was 8.91 microg/L in non-smokers; smokers exhibited significantly lower levels. The upper reference limit for individuals expressing CA19.9 was 28.3 kU/L.

    Conclusions: For AFP, CA125 and CA19.9, the reference levels obtained were close to previously reported reference ranges. Smoking and age were confirmed as covariates for CEA. The associations between MUC1 with age and BMI and between NSE and smoking have not been reported previously.

    Scandinavian journal of clinical and laboratory investigation 2008;68;8;703-13

  • Anti-vimentin antibodies and neuron-specific enolase in children with neurofibromatosis type-1.

    Kotaska K, Petrak B, Kukacka J, Kraus J and Prusa R

    Department of Clinical Biochemistry and Pathobiochemistry, University Hospital Motol, 2nd Medical Faculty, Charles University, Prague, Czech Republic. kotaska@email.cz

    Objectives: The aim of the study was to investigate the relationship of serum levels of neuron-specific enolase, anti-vimentin IgG, and anti-vimentin IgM antibodies in patients with neurofibromatosis type 1 and associated tumors (optic glioma, and plexiform neurofibroma).

    Methods: Measurement of neuron-specific enolase and anti-vimentin antibodies were performed in 131 children and adolescents (67 males, mean age 10 years, range 4-19 years; 64 females, mean age 11 years, range 1-20 years) with three different forms of neurofibromatosis type 1 and in control group of 40 individuals (20 males, mean age 9 years, range 1-19 years and 20 females, mean age 12 years, range 3-18 years).

    Results: Anti-vimentin IgG, IgM antibodies and NSE showed similar ability to distinguish between neurofibromatosis type 1 and tumors associated with neurofibromatosis type 1. (AUC=0.57, AUC=0.52 and AUC=0.59 respectively). NSE showed better diagnostic efficiency (AUC=0.68) than the anti-vimentin IgG and anti-vimentin IgM. (AUC=0.63 and AUC=0.56 respectively). Anti-vimentin IgG and IgM antibodies showed higher sensitivity (87.5% and 87.2%) at the cut off value than the NSE (54%). On the contrary, NSE showed higher specificity at the cut off value than both the anti-vimentin IgG and IgM (71% vs. 22.5% and 16% respectively).

    Conclusions: Anti-vimentin IgG and IgM and neuron-specific enolase are relevant markers in investigation of the patients with neurofibromatosis type 1 and associated tumors.

    Neuro endocrinology letters 2007;28;6;761-4

  • Enolase and arrestin are novel nonmyelin autoantigens in multiple sclerosis.

    Forooghian F, Cheung RK, Smith WC, O'Connor P and Dosch HM

    Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada. farzin.forooghian@utoronto.ca

    Introduction: Although myelin autoimmunity is known to be a major factor in the pathogenesis of multiple sclerosis (MS), the role of nonmyelin antigens is less clear. Given the complexity of this disease, it is possible that autoimmunity against nonmyelin antigens also has a pathogenic role. Autoantibodies against enolase and arrestin have previously been reported in MS patients. The T-cell response to these antigens, however, has not been established.

    Methods: Thirty-five patients with MS were recruited, along with thirty-five healthy controls. T-cell proliferative responses against non-neuronal enolase, neuron-specific enolase (NSE), retinal arrestin, beta-arrestin, and myelin basic protein were determined.

    Results: MS patients had a greater prevalence of positive T-cell proliferative responses to NSE, retinal arrestin, and beta-arrestin than healthy controls (p<0.0001). The proliferative response against NSE, retinal arrestin, and beta-arrestin correlated with the response against myelin basic protein (p < or = 0.004). Furthermore, the proliferative response against retinal arrestin was correlated to beta-arrestin (p<0.0001), whereas there was no such correlation between non-neuronal enolase and NSE (p = 0.23).

    Discussion: There is accumulating evidence to suggest that the pathogenesis of MS involves more than just myelin autoimmunity/destruction. Autoimmunity against nonmyelin antigens may be a component of this myriad of immunopathological events. NSE, retinal arrestin, and beta-arrestin are novel nonmyelin autoantigens that deserve further investigation in this respect. Autoimmunity against these antigens may be linked to neurodegeneration, defective remyelination, and predisposition to uveitis in multiple sclerosis. Further investigation of the role of these antigens in MS is warranted.

    Funded by: NEI NIH HHS: R01 EY006225, R01 EY006225-22, R01 EY014864

    Journal of clinical immunology 2007;27;4;388-96

  • Fluoride inhibition of enolase: crystal structure and thermodynamics.

    Qin J, Chai G, Brewer JM, Lovelace LL and Lebioda L

    Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, USA.

    Enolase is a dimeric metal-activated metalloenzyme which uses two magnesium ions per subunit: the strongly bound conformational ion and the catalytic ion that binds to the enzyme-substrate complex inducing catalysis. The crystal structure of the human neuronal enolase-Mg2F2P(i) complex (enolase fluoride/phosphate inhibitory complex, EFPIC) determined at 1.36 A resolution shows that the combination of anions effectively mimics an intermediate state in catalysis. The phosphate ion binds in the same site as the phosphate group of the substrate/product, 2-phospho-D-glycerate/phosphoenolpyruvate, and induces binding of the catalytic Mg2+ ion. One fluoride ion bridges the structural and catalytic magnesium ions while the other interacts with the structural magnesium ion and the ammonio groups of Lys 342 and Lys 393. These fluoride ion positions correspond closely to the positions of the oxygen atoms of the substrate's carboxylate moiety. To relate structural changes resulting from fluoride, phosphate, and magnesium ions binding to those that are induced by phosphate and magnesium ions alone, we also determined the structure of the human neuronal enolase-Mg2P(i) complex (enolase phosphate inhibitory complex, EPIC) at 1.92 A resolution. It shows the closed conformation in one subunit and a mixture of open and semiclosed conformations in the other. The EPFIC dimer is essentially symmetric while the EPIC dimer is asymmetric. Isothermal titration calorimetry data confirmed binding of four fluoride ions per dimer and yielded Kb values of 7.5 x 10(5) +/- 1.3 x 10(5), 1.2 x 10(5) +/- 0.2 x 10(5), 8.6 x 10(4) +/- 1.6 x 10(4), and 1.6 x 10(4) +/- 0.7 x 10(4) M(-1). The different binding constants indicate negative cooperativity between the subunits; the asymmetry of EPIC supports such an interpretation.

    Funded by: NCI NIH HHS: CA076560, R01 CA076560, R01 CA076560-07

    Biochemistry 2006;45;3;793-800

  • Serum neuron-specific enolase as early predictor of outcome after in-hospital cardiac arrest: a cohort study.

    Rech TH, Vieira SR, Nagel F, Brauner JS and Scalco R

    Serviço de Medicina Intensiva, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Largo Eduardo Z, Faraco, Porto Alegre, RS, 90035-903, Brazil. tatianarech@terra.com.br

    Introduction: Outcome after cardiac arrest is mostly determined by the degree of hypoxic brain damage. Patients recovering from cardiopulmonary resuscitation are at great risk of subsequent death or severe neurological damage, including persistent vegetative state. The early definition of prognosis for these patients has ethical and economic implications. The main purpose of this study was to investigate the prognostic value of serum neuron-specific enolase (NSE) in predicting outcomes in patients early after in-hospital cardiac arrest.

    Methods: Forty-five patients resuscitated from in-hospital cardiac arrest were prospectively studied from June 2003 to January 2005. Blood samples were collected, at any time between 12 and 36 hours after the arrest, for NSE measurement. Outcome was evaluated 6 months later with the Glasgow outcome scale (GOS). Patients were divided into two groups: group 1 (unfavorable outcome) included GOS 1 and 2 patients; group 2 (favorable outcome) included GOS 3, 4 and 5 patients. The Mann-Whitney U test, Student's t test and Fisher's exact test were used to compare the groups.

    Results: The Glasgow coma scale scores were 6.1 +/- 3 in group 1 and 12.1 +/- 3 in group 2 (means +/- SD; p < 0.001). The mean time to NSE sampling was 20.2 +/- 8.3 hours in group 1 and 28.4 +/- 8.7 hours in group 2 (p = 0.013). Two patients were excluded from the analysis because of sample hemolysis. At 6 months, favorable outcome was observed in nine patients (19.6%). Thirty patients (69.8%) died and four (9.3%) remained in a persistent vegetative state. The 34 patients (81.4%) in group 1 had significantly higher NSE levels (median 44.24 ng/ml, range 8.1 to 370) than those in group 2 (25.26 ng/ml, range 9.28 to 55.41; p = 0.034).

    Conclusion: Early determination of serum NSE levels is a valuable ancillary method for assessing outcome after in-hospital cardiac arrest.

    Critical care (London, England) 2006;10;5;R133

  • Proteomic analysis of SUMO4 substrates in HEK293 cells under serum starvation-induced stress.

    Guo D, Han J, Adam BL, Colburn NH, Wang MH, Dong Z, Eizirik DL, She JX and Wang CY

    Center for Biotechnology and Genomic Medicine, Medical College of Georgia, 1120 15th Street, CA4098, Augusta, GA 30912, USA.

    The substrates of SUMO4, a novel member for the SUMO gene family, were characterized in HEK293 cells cultured under serum starvation by proteomic analysis. We identified 90 SUMO4 substrates including anti-stress proteins such as antioxidant enzymes and molecular chaperones or co-chaperones. The substrates also include proteins involved in the regulation of DNA repair and synthesis, RNA processing, protein degradation, and glucose metabolism. Several SUMO4-associated transcription factors were characterized by Western blot analyses. AP-1 was selected for in vitro conjugation assays to confirm SUMO4 sumoylation of these transcription factors. Further functional analyses of the transcription factors suggested that SUMO4 sumoylation represses AP-1 and AP-2alpha transcriptional activity, but enhances GR DNA binding capacity. These results demonstrate that SUMO4 sumoylation may play an important role in the regulation of intracellular stress.

    Biochemical and biophysical research communications 2005;337;4;1308-18

  • A human protein-protein interaction network: a resource for annotating the proteome.

    Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H and Wanker EE

    Max Delbrueck Center for Molecular Medicine, 13092 Berlin-Buch, Germany.

    Protein-protein interaction maps provide a valuable framework for a better understanding of the functional organization of the proteome. To detect interacting pairs of human proteins systematically, a protein matrix of 4456 baits and 5632 preys was screened by automated yeast two-hybrid (Y2H) interaction mating. We identified 3186 mostly novel interactions among 1705 proteins, resulting in a large, highly connected network. Independent pull-down and co-immunoprecipitation assays validated the overall quality of the Y2H interactions. Using topological and GO criteria, a scoring system was developed to define 911 high-confidence interactions among 401 proteins. Furthermore, the network was searched for interactions linking uncharacterized gene products and human disease proteins to regulatory cellular pathways. Two novel Axin-1 interactions were validated experimentally, characterizing ANP32A and CRMP1 as modulators of Wnt signaling. Systematic human protein interaction screens can lead to a more comprehensive understanding of protein function and cellular processes.

    Cell 2005;122;6;957-68

  • Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules.

    Zhang Y, Wolf-Yadlin A, Ross PL, Pappin DJ, Rush J, Lauffenburger DA and White FM

    Biological Engineering Division, Massachusetts Institute of Technnology, Cambridge, Massachusetts 02139, USA.

    Ligand binding to cell surface receptors initiates a cascade of signaling events regulated by dynamic phosphorylation events on a multitude of pathway proteins. Quantitative features, including intensity, timing, and duration of phosphorylation of particular residues, may play a role in determining cellular response, but experimental data required for analysis of these features have not previously been available. To understand the dynamic operation of signaling cascades, we have developed a method enabling the simultaneous quantification of tyrosine phosphorylation of specific residues on dozens of key proteins in a time-resolved manner, downstream of epidermal growth factor receptor (EGFR) activation. Tryptic peptides from four different EGFR stimulation time points were labeled with four isoforms of the iTRAQ reagent to enable downstream quantification. After mixing of the labeled samples, tyrosine-phosphorylated peptides were immunoprecipitated with an anti-phosphotyrosine antibody and further enriched by IMAC before LC/MS/MS analysis. Database searching and manual confirmation of peptide phosphorylation site assignments led to the identification of 78 tyrosine phosphorylation sites on 58 proteins from a single analysis. Replicate analyses of a separate biological sample provided both validation of this first data set and identification of 26 additional tyrosine phosphorylation sites and 18 additional proteins. iTRAQ fragment ion ratios provided time course phosphorylation profiles for each site. The data set of quantitative temporal phosphorylation profiles was further characterized by self-organizing maps, which resulted in identification of several cohorts of tyrosine residues exhibiting self-similar temporal phosphorylation profiles, operationally defining dynamic modules in the EGFR signaling network consistent with particular cellular processes. The presence of novel proteins and associated tyrosine phosphorylation sites within these modules indicates additional components of this network and potentially localizes the topological action of these proteins. Additional analysis and modeling of the data generated in this study are likely to yield more sophisticated models of receptor tyrosine kinase-initiated signal transduction, trafficking, and regulation.

    Funded by: NCI NIH HHS: CA96504; NIDDK NIH HHS: DK070172, DK42816; NIGMS NIH HHS: GM68762

    Molecular & cellular proteomics : MCP 2005;4;9;1240-50

  • Nonspecific increase of systemic neuron-specific enolase after trauma: clinical and experimental findings.

    Pelinka LE, Hertz H, Mauritz W, Harada N, Jafarmadar M, Albrecht M, Redl H and Bahrami S

    Ludwig Boltzmann Institute for Experimental and Clinical Traumatology at the Research Centre of the Allgemeine Unfallversicherungsanstalt, A-1200, Vienna, Austria. lindapel@via.at

    The aim of this clinical and experimental study was to determine whether systemic neuron-specific enolase (NSE) is a useful early marker of traumatic brain injury (TBI) and whether NSE is affected by ischemia/reperfusion damage of abdominal organs. Our study included patients with and without TBI (verified by computerized tomography) admitted within 6 h after trauma and male Sprague-Dawley rats with ischemia and reperfusion of the abdominal organs liver, gut, or kidney. Thirty-eight study patients included 13 with isolated TBI and 18 patients with multiple trauma and TBI. Seven patients had multiple trauma but no TBI. Fifteen rats were anaesthetized and subjected to isolated ischemia of the liver, gut, or kidney (n = 5 each) for 1 h, followed by reperfusion for 3 h. In patients, NSE increased over 2-fold versus the upper normal limit (10 microg/L) within 6 h after trauma, regardless of whether TBI had occurred or not. In rats, NSE increased over 3-fold versus laboratory controls during ischemia of the liver and kidney (both P < 0.0005), but not of the gut. NSE increased over 2-fold after onset of reperfusion of the liver and kidney (both P < 0.05), but not of the gut and increased over 3-fold after 3 h of reperfusion of the liver, gut (both P < 0.005), and kidney (P < 0.0005). Our data show that systemic NSE increases to similar degrees with and without TBI. Therefore, NSE is not a useful early marker of TBI in multiple trauma.

    Shock (Augusta, Ga.) 2005;24;2;119-23

  • Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.

    Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD and Comb MJ

    Cell Signaling Technology Inc., 166B Cummings Center, Beverly, Massachusetts 01915, USA.

    Tyrosine kinases play a prominent role in human cancer, yet the oncogenic signaling pathways driving cell proliferation and survival have been difficult to identify, in part because of the complexity of the pathways and in part because of low cellular levels of tyrosine phosphorylation. In general, global phosphoproteomic approaches reveal small numbers of peptides containing phosphotyrosine. We have developed a strategy that emphasizes the phosphotyrosine component of the phosphoproteome and identifies large numbers of tyrosine phosphorylation sites. Peptides containing phosphotyrosine are isolated directly from protease-digested cellular protein extracts with a phosphotyrosine-specific antibody and are identified by tandem mass spectrometry. Applying this approach to several cell systems, including cancer cell lines, shows it can be used to identify activated protein kinases and their phosphorylated substrates without prior knowledge of the signaling networks that are activated, a first step in profiling normal and oncogenic signaling networks.

    Funded by: NCI NIH HHS: 1R43CA101106

    Nature biotechnology 2005;23;1;94-101

  • The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

    Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J and MGC Project Team

    The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

    Funded by: PHS HHS: N01-C0-12400

    Genome research 2004;14;10B;2121-7

  • Expression, purification and the 1.8 angstroms resolution crystal structure of human neuron specific enolase.

    Chai G, Brewer JM, Lovelace LL, Aoki T, Minor W and Lebioda L

    Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208, USA.

    Human neuron-specific enolase (NSE) or isozyme gamma has been expressed with a C-terminal His-tag in Escherichia coli. The enzyme has been purified, crystallized and its crystal structure determined. In the crystals the enzyme forms the asymmetric complex NSE x Mg2 x SO4/NSE x Mg x Cl, where "/" separates the dimer subunits. The subunit that contains the sulfate (or phosphate) ion and two magnesium ions is in the closed conformation observed in enolase complexes with the substrate or its analogues; the other subunit is in the open conformation observed in enolase subunits without bound substrate or analogues. This indicates negative cooperativity for ligand binding between subunits. Electrostatic charge differences between isozymes alpha and gamma, -19 at physiological pH, are concentrated in the regions of the molecular surface that are negatively charged in alpha, i.e. surface areas negatively charged in alpha are more negatively charged in gamma, while areas that are neutral or positively charged tend to be charge-conserved.

    Journal of molecular biology 2004;341;4;1015-21

  • Complete sequencing and characterization of 21,243 full-length human cDNAs.

    Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T and Sugano S

    Helix Research Institute, 1532-3 Yana, Kisarazu, Chiba 292-0812, Japan.

    As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at approximately 58% compared with a peak at approximately 42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at approximately 42%, relatively low compared with that of protein-coding cDNAs.

    Nature genetics 2004;36;1;40-5

  • Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia.

    Tiainen M, Roine RO, Pettilä V and Takkunen O

    Department of Neurology, Helsinki University Central Hospital, Finland. marjaana.tiainen@hus.fi

    High serum levels of neuron-specific enolase (NSE) and S-100B protein are known to be associated with ischemic brain injury and poor outcome after cardiac arrest. Therapeutic hypothermia has been shown to improve neurological outcome after cardiac arrest. The aim of this study was to evaluate the effect of therapeutic hypothermia on levels of serum NSE and S-100B protein, their time course, and their prognostic value in predicting unfavorable outcome after out-of-hospital cardiac arrest.

    Methods: Seventy patients resuscitated from ventricular fibrillation were randomly assigned to hypothermia of 33+/-1 degrees C for 24 hours or to normothermia. Serum NSE and S-100B were sampled at 24, 36, and 48 hours after cardiac arrest. Neurological outcome was dichotomized into good or poor at 6 months after cardiac arrest.

    Results: The levels of NSE (P=0.007 by analysis of variance for repeated measurements) but not S-100B were lower in hypothermia- than normothermia-treated patients. A decrease in NSE values between 24 and 48 hours was observed in 30 of 34 patients (88%) in the hypothermia group and in 16 of 32 patients (50%) in the normothermia group (P<0.001). The decrease in NSE values was associated with good outcome at 6 months after cardiac arrest (P=0.005), recovery of consciousness (P<0.001), and survival for at least 6 months after cardiac arrest (P=0.012).

    Conclusions: Decreasing levels of serum NSE but not S-100B over time may indicate selective attenuation of delayed neuronal death by therapeutic hypothermia in victims of cardiac arrest.

    Stroke 2003;34;12;2881-6

  • Neuron-specific enolase, nucleotides, nucleosides, purine bases, oxypurines and uric acid concentrations in cerebrospinal fluid of children with meningitis.

    Rodríguez-Núñez A, Cid E, Rodríguez-García J, Camiña F, Rodríguez-Segade S and Castro-Gago M

    Department of Pediatrics, Hospital Clínico Universitario de Santiago, Complejo Hospitalario Universitario de Santiago, Choupana, s/n, 15706, Santiago de Compostela, Spain.

    To determine the effects of meningitis on cerebral energy metabolism, cerebrospinal fluid concentrations of adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and urate were determined by high-performance liquid chromatography, and neuron-specific enolase by an enzyme immunoassay method, in 100 children with meningitis (45 bacterial, 46 viral and nine tuberculous), aged between 1 month and 13 years, and in 160 age-matched controls. Compared with controls, patients with bacterial meningitis showed high concentrations of hypoxanthine, xanthine and urate; patients with viral meningitis showed high concentrations of inosine, guanosine, xanthine, urate and neuron-specific enolase; and patients with tuberculous meningitis showed very high concentrations of inosine, xanthine and urate. Xanthine and urate concentrations were significantly higher in patients with tuberculous meningitis than in patients with viral or bacterial meningitis. These results suggest that in the acute stage of bacterial, viral and tuberculous meningitis, neuronal energy metabolism may be altered. The measurement of cerebrospinal xanthine and uric acid concentrations may be useful for the early diagnosis of a tuberculous origin.

    Brain & development 2003;25;2;102-6

  • Technical performance and diagnostic utility of the new Elecsys neuron-specific enolase enzyme immunoassay.

    Muley T, Ebert W, Stieber P, Raith H, Holdenrieder S, Nagel D, Fürst H, Roth HJ, Luthe H, Blijenberg BG, Gurr E, Uhl W, von Pawel J and Drings P

    Thoraxklinik-Heidelberg gGmbH, Heidelberg, Germany.

    This international multicenter study was designed to evaluate the technical performance of the new double-monoclonal, single-step Elecsys neuron-specific enolase (NSE) enzyme immunoassay (EIA) and to assess its utility as a sensitive and specific test for the diagnosis of small-cell lung cancer (SCLC). Intra- and interassay coefficients of variation, determined in five control or serum specimens in six laboratories, ranged from 0.7 to 5.3 (inter-laboratory median: 1.3%) and from 1.3 to 8.5 (inter-laboratory median: 3.4%), respectively. Laboratory-to-laboratory comparability was excellent with respect to recovery and inter-assay coefficients of variation. The test was linear between 0.0 and 320 ng/ml (highest measured concentration). There was a significant correlation between NSE concentrations measured using the Elecsys NSE and the established Cobas Core NSE EIA II in all subjects (n = 723) and in patients with lung cancer (n = 333). However, NSE concentrations were systematically lower (approximately 9%) with the Elecsys NSE than with the comparison test. Based on a specificity of 95% in comparison with the group suffering from benign lung diseases (n = 183), the cut-off value for the discrimination between malignant and benign conditions was set at 21.6 ng/ml. NSE was raised in 73.4% of SCLC patients (n = 188) and was significantly higher (p < 0.01) in extensive (87.8%) as opposed to limited disease (56.7%). NSE was also elevated in 16.0% of the cases with non-small cell lung cancer (NSCLC, n = 374). It is concluded that the Elecsys NSE EIA is a reliable and accurate diagnostic procedure for the measurement of NSE in serum samples. The special merits of this new assay are the wide measuring range (according to manufacturer's declaration up to 370 ng/ml) and a short incubation time of 18 min.

    Clinical chemistry and laboratory medicine 2003;41;1;95-103

  • Clinical significance of serum neuron-specific enolase in patients with adult T-cell leukemia.

    Fujiwara H, Arima N, Ohtsubo H, Matsumoto T, Kukita T, Kawada H, Imaizumi R, Ozaki A, Matsushita K and Tei C

    First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.

    The present study examines the clinical significance of serum neuron-specific enolase (NSE) in patients with adult T cell-leukemia (ATL). Serum NSE values were measured using a radioimmunoassay in 35 patients (acute type, n = 15; lymphoma type, n = 10; chronic type, n = 10) and in 7 controls carrying T lymphotropic virus type-1 (HTLV-1). Serum NSE values >10 ng/mL were detected in 9 of 15 patients with acute type (60%), 5 of 10 with lymphoma type (50%), and in one of 10 patients with chronic type (10%) ATL, but in none of the HTLV-1 carriers. Contrary to previous findings demonstrating that 20% of patients with non-Hodgkin's lymphoma (NHL) had positive serum NSE, the frequency of a high NSE value in patients with acute and lymphoma type ATL was much higher (60% and 50%, respectively). The serum NSE value positively correlated with serum thymidine kinase activity (TK) and serum soluble interleukin-2 receptor (sIL-2R) levels (P < 0.04 and P < 0.01, respectively). Serum NSE values at the initial diagnosis were adversely related to overall survival time according to the log-rank test (P < 0.02). Pathological examinations demonstrated that both patients with anaplastic large cell lymphoma type ATL had cytoplasmic NSE and CD30 markers on cell membranes. These findings suggest that serum NSE is partially produced by ATL cells and that ATL tumor cells seem preferentially produce NSE compared with other NHL cells. Serum NSE may be a novel marker of disease aggressiveness as well as a prognostic factor for ATL.

    American journal of hematology 2002;71;2;80-4

  • Serum time course of two brain-specific proteins, alpha(1) brain globulin and neuron-specific enolase, in tick-born encephalitis and Lyme disease.

    Chekhonin VP, Zhirkov YA, Belyaeva IA, Ryabukhin IA, Gurina OI and Dmitriyeva TB

    Laboratory of Immunochemistry, Serbsky National Research Centre for Social and Forensic Psychiatry, Kropotkinsky per. 23, 119839 Moscow, Russia. chekhonin@aport.ru

    Methods: Time courses of the serum concentrations of two brain-specific proteins (BSP), alpha(1) brain globulin (alpha(1)BG, an astroglial marker) and neuron-specific enolase (NSE), were studied in patients with severe tick-born encephalitis (TBE) and Lyme disease (LD; neuroborreliosis). The concentrations were determined on the second day of the acute phase and then on the 7th, 12th, 18th, and 23rd days. Apparent rate constants for the elimination of the BSP from blood (k(e)) were calculated with the non-linear regression.

    Results: In patients with TBE, the highest serum concentrations of alpha(1)BG and NSE, observed on the second day, were followed by their monotonic decrease to the normal levels reached by the 23rd day. The mean k(e) values for alpha(1)BG and NSE were found to be significantly different (0.086+/-0.003 vs. 0.057+/-0.006 day(-1), respectively; p<0.05). Higher serum levels of both BSP were observed in the more severe clinical cases and in the cases with unfavorable outcomes. Similar profiles were also observed for the serum alpha(1)BG and NSE in LD.

    Conclusions: These results suggest that, in the patients examined, the blood-brain barrier was partially impaired; the quantitative parameters of the serum BSP time courses can be indicative of the extents of the neuronal and/or glial lesions.

    Clinica chimica acta; international journal of clinical chemistry 2002;320;1-2;117-25

  • Enhanced expression of neuron-specific enolase (NSE) in pyothorax-associated lymphoma (PAL).

    Nakatsuka S, Nishiu M, Tomita Y, Miwa H, Takakuwa T, Iuchi K, Yamamoto S and Aozasa K

    Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.

    Pyothorax-associated lymphoma (PAL) is a B-cell lymphoma of mostly large cell type developing in the pleural cavity of patients with long-standing pyothorax. Neuron-specific enolase (NSE) is an enolase comprising gamma subunit and is located at high levels in neuronal and neuroendocrine cells, together with their neoplasias. Expression of NSE at protein and mRNA levels was examined in PAL and other types (non-PAL) of non-Hodgkin's lymphomas. In PAL, serum levels of NSE were elevated (5.32 to 168.0, mean 42.6 ng/ml) and tended to decrease after incisional biopsy followed by chemotherapy (2.38 to 195.5, mean 34.1 ng/ml). Two cell lines established from two cases of PAL produced and secreted NSE in the culture medium. Immunohistochemistry revealed that the positive rate for NSE staining in PAL (10 of 14 cases, 71.4%) was significantly higher than that in non-PAL cases (6 of 38 cases, 15.8%) (P < 0.01). RT-PCR analysis showed that the expression levels of NSE mRNA in two cell lines and a biopsy sample from PAL were rather similar to those of the control samples from non-neoplastic lymph nodes. These findings suggest the posttranscriptional regulation of NSE in PAL. Thus, an elevation of serum NSE level in patients with chronic pyothorax may be an indicator of PAL development.

    Japanese journal of cancer research : Gann 2002;93;4;411-6

  • Expression in the placenta of neuronal markers for perinatal brain damage.

    Wijnberger LD, Nikkels PG, van Dongen AJ, Noorlander CW, Mulder EJ, Schrama LH and Visser GH

    Department of Obstetrics, University Medical Center Utrecht, The Netherlands. l.wijnberger@dog.azu.nl

    Determination of S-100 a and b and neuron-specific enolase (NSE) in (cord) blood and amniotic fluid has been used to assess neonatal neuronal damage after compromising conditions. However, these proteins are not only found in nervous tissue, and their expression in placenta and umbilical cord has never been investigated. In this study, S-100 (a and b) and NSE expression in human cord and placental tissue was studied by immunohistochemical analysis. Similar analysis was performed using two other brain-specific markers: glial fibrillary acidic protein and growth-associated protein B-50 (also known as GAP-43 or neuromodulin). Tissue was derived after elective cesarean section in seven women of different gestational ages after uncomplicated or complicated pregnancy. S-100 a and b and NSE immunoreactivity was found in several cell types and structures in the umbilical cord as well as in the placenta of all seven cases. Glial fibrillary acidic protein and B-50 showed no immunoreactivity. These data are of importance for interpreting findings of studies in which S-100 or NSE levels in cord blood or amniotic fluid have been related to neuronal damage in the neonate. The increased levels found may just as well be caused by leakage from placenta or umbilical cord as be caused by brain damage. We conclude that S-100 a and b and NSE are not suitable markers for neonatal brain damage. Brain-restricted proteins such as glial fibrillary acidic protein and B-50 seem more promising.

    Pediatric research 2002;51;4;492-6

  • Pituitary autoantibodies in lymphocytic hypophysitis target both gamma- and alpha-Enolase - a link with pregnancy?

    O'Dwyer DT, Clifton V, Hall A, Smith R, Robinson PJ and Crock PA

    Paediatric Endocrine Unit, John Hunter Children's Hospital, NSW, Australia.

    The first target autoantigen to have been identified in lymphocytic hypophysitis is a 49 kDa protein, identified as alpha-enolase. Pituitary autoimmunity is strongly associated with pregnancy and we have shown that pituitary autoantibodies from patients with peripartum lymphocytic hypophysitis also recognise enolase in the placenta. Enolase exists in different forms as a number of isoenzymes, which are homo- or heterodimers of three subunits, alpha, beta and gamma. alphaalpha-enolase is ubiquitous, betabeta-enolase is muscle-specific and gammagamma-enolase, which is restricted to neuronal tissue and neuroendocrine cells, is known as neuron-specific enolase (NSE). NSE is expressed in normal human pituitary and pituitary neoplasms. The current study investigated which isoforms of enolase in pituitary and placenta reacted with the sera of patients with lymphocytic hypophysitis. Immunoblotting of two-dimensional gels of human pituitary cytosolic proteins showed that autoantibodies in patient sera react with both an acidic form, and more neutral forms of enolase. Immunoblotting with a monoclonal antibody to NSE confirmed the identity of the acidic enolase isoform as the gammagamma-isoform in both pituitary and placental samples. Gamma-enolase, i.e. NSE, was detected by immunohistochemistry in term placenta in decidua, syncytiotrophoblasts, anchoring villi and terminal villi. Our study is the first to describe the cellular localisation of NSE in normal human placenta, thus establishing a direct link between pituitary and placental autoantigens. This link provides a theoretical basis for the strong prediliction of lymphocytic hypophysitis to occur during or after pregnancy.

    Archives of physiology and biochemistry 2002;110;1-2;94-8

  • Neuroblastoma: a single institution's experience with 128 children and an evaluation of clinical and biological prognostic factors.

    Lau L

    Department of Oncology, Royal Alexandra Hospital for Children, New South Wales, Australia. lorettalau48@hotmail.com

    Between 1985 and 1999, 128 children with neuroblastoma were treated at the Royal Alexandra Hospital for Children. The objective of this retrospective study was to report on a single institution's experience with neuroblastoma and to evaluate clinical and biological prognostic factors using univariate and multivariate assessment. Fifty-two percent presented with localized disease, 41% had stage IV disease, and 7% had stage IVs disease. The 5-year overall survival rate was 65%. Significant prognostic factors in univariate analysis included stage, site, histology, N-myc amplification, neuron-specific enolase (NSE), lactate dehydrogenase (LDH), and urinary dopamine. In multivariate assessment, the adjusted hazard ratio was 3.5 (95 %CI 1.4-8.5) for N-myc amplification, 8.7 (95% CI 3.0-25) for NSE > 300 ng/mL, and 3.6 (95% CI 1.3-10) for-LDH > 3000 U/L. This study confirmed that survival was heavily influenced by closely interrelated clinical and biological factors. Prospective studies including more recently identified molecular prognostic factors are warranted to predict the biological heterogeneity of neuroblastoma.

    Pediatric hematology and oncology 2002;19;2;79-89

  • Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination.

    Ansari-Lari MA, Shen Y, Muzny DM, Lee W and Gibbs RA

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. ma029926@bcm.tmc.edu

    The detailed genomic organization of a gene-dense region at human chromosome 12p13, spanning 223 kb of contiguous sequence, was determined. This region is composed of 20 genes and several other expressed sequences. Experimental tools including RT-PCR and cDNA sequencing, combined with gene prediction programs, were utilized in the analysis of the sequence. Various computer software programs were employed for sequence similarity searches and functional predictions. The high number of genes with diverse functions and complex transcriptional patterns make this region ideal for addressing challenges of gene discovery and genomic characterization amenable to large-scale sequence analysis.

    Funded by: NHGRI NIH HHS: R01 HG01459

    Genome research 1997;7;3;268-80

  • Axotomy induces intranuclear immunolocalization of neuron-specific enolase in facial and hypoglossal neurons of the rat.

    Angelov DN, Neiss WF, Gunkel A, Guntinas-Lichius O and Stennert E

    Institut I für Anatomie, Nasen- und Ohrenheilkunde der Universität zu Köln, Germany.

    Neuron-specific enolase as an enzyme of the glycolytic pathway is localized in the cytoplasm of nerve cells, but not in the cell nucleus. We have applied immunocytochemistry with 1:64,000 polyclonal anti-rat neuron-specific enolase to the brainstem of male and female adult Wistar rats following: (a) transection of the facial nerve with immediate microsurgical nerve suture (facial-facial anastomosis), (b) transection of the hypoglossal nerve with immediate suture (hypoglossal-hypoglossal anastomosis) and (c) transection of the facial and hypoglossal nerve with immediate suture of the proximal hypoglossal to the distal facial nerve stump (hypoglossal-facial anastomosis). Studying the intracellular immunolocalization of neuron-specific enolase in neurons of the facial and hypoglossal nucleus we detected that (1) in normal rats about 20% of all facial and hypoglossal neurons display not only cytoplasmic, but also intranuclear neuron-specific enolase-like immunoreactivity and (2) following any axotomy of the facial or hypoglossal peripheral nerve, the perikarya of all injured motoneurons react by an outstanding increase of neuron-specific enolase-like immunoreactivity in the karyoplasm. Similar findings were obtained in experiments on non-fixed cultured Neuro-2a cells that had been lesioned with hydrogen peroxide. Counting the absolute numbers of normal and reactive neurons at 1-365 days post axotomy revealed that the increase of neuron-specific enolase in neuronal cell nuclei is temporary and reversible. It is first detected at 2 days post axotomy, reaches its maximum at 10-18 days post axotomy and is no longer evident 56 days following surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

    Journal of neurocytology 1994;23;4;218-33

  • Detection of neuron-specific gamma-enolase messenger ribonucleic acid in normal human leukocytes by polymerase chain reaction amplification with nested primers.

    Pechumer H, Bender-Götze C and Ziegler-Heitbrock HW

    Pediatric Outpatient Clinic, University of Munich, Germany.

    Background: NNE (non-neuronal alpha-enolase) is a glycolytic enzyme detected in most tissues. NSE (neuron-specific gamma-enolase) is detected in normal neurons and tumors such as neuroblastoma. Staining with antibodies against NSE is therefore used to detect neuroblastoma cells invading bone marrow. Since staining of normal leukocytes has been reported we asked whether bona fide NSE is in fact expressed in normal blood and marrow.

    We designed nested coding region specific primers for NSE and NNE and, after reverse transcription of mRNA, we amplified the coding region between these primers in a semi-nested polymerase chain reaction. In order to distinguish both iso-mRNAs from each other, we amplified a long (1,047 bp) template in a first round of 30 cycles with primers specific for NNE or NSE. One percent of this product was used in a second round of 30 cycles in which both sense primers and two nested anti-sense primers of alternate specificities yielding shorter products of discernible sizes (768 bp or 619 bp) were added together in the same reaction tube. With this combination of four primers, only that shorter product was amplified to visibility, the specificity of which was homologous to the template produced in the first 30 cycles. Restriction enzyme digestion of the amplified products was used to verify this polymerase chain reaction-based approach for the distinction of isoforms of RNA.

    Results: This semi-nested polymerase chain reaction clearly allows for the distinction of mRNA for NNE or NSE and shows the presence of transcripts for NSE in normal human leukocytes from blood and bone marrow.

    Conclusions: This method exploiting short stretches of nucleotide differences in the coding regions for priming can more generally be applied to the distinction of all isoforms of RNA where nested specific primers can be designed. However, the presence of NSE specific transcripts in normal human leukocytes invalidates the use of this highly sensitive method as a disease marker in neuroblastoma.

    Laboratory investigation; a journal of technical methods and pathology 1993;69;6;743-9

  • Purification and partial amino acid sequence of suppressive lymphokine from a CD8+ CD57+ human T hybridoma.

    Quan CP, Watanabe S, Vuillier F, Pires R, Matsuo T, Stanislawski M, Pillot J and Bouvet JP

    Institut Pasteur Paris Unité d'Immunologie Microbienne, France.

    A T-suppressor (TS) lymphokine was purified from the supernatant of a T hybridoma established from CD3+ CD8+ CD57+ lymphocytes of a healthy bone marrow transplant patient. Using polyclonal rabbit antibodies, raised against a TS-enriched preparation, a specific protein of 47,000 MW was identified, which was used to prepare monoclonal antibodies. The screening of hybridomas was carried out by strip-ELISA, in which the 47,000 MW band, transferred on a membrane, served as antigen. One of these monoclonal antibodies (IgM kappa) was selected for purification of the native TS molecule, which exhibited the high suppressive activity on the phytohaemagglutinin (PHA) and alloantigen responses of peripheral blood lymphocytes. The establishment of amino acid sequences of five trypsinized cleavage peptides confirmed that this protein has not been previously identified. This lymphokine--also detected in the supernatant of normal CD8+ CD57+ lymphocytes--is likely involved in bone marrow transplantation tolerance.

    Immunology 1993;78;2;205-9

  • Complete structure of the human gene encoding neuron-specific enolase.

    Oliva D, Calì L, Feo S and Giallongo A

    Istituto di Biologia dello Sviluppo del Consiglio Nazionale delle Richerche, Palermo, Italy.

    At least three genes encode the different isoforms of the glycolytic enzyme enolase. We have isolated the gene for the human gamma- or neuron-specific enolase and determined the nucleotide sequence from upstream to the 5' end to beyond the polyadenylation site. The gene contains 12 exons distributed over 9213 nucleotides. Introns occur at positions identical to those reported for the homologous rat gene, as well as for the human alpha- or nonneuronal enolase gene, supporting the existence of a single ancestor for the members of this gene family. Primer extension analysis indicates that the gene has multiple start sites. The putative promoter region lacks canonical TATA and CAAT boxes, is very G + C-rich, and contains several potential regulatory sequences. Furthermore, an inverted Alu sequence is present approximately 572 nucleotides upstream of the major start site. A comparison of the 5'-flanking region of the human gamma-enolase gene with the same region of the rat gene revealed a high degree of sequence conservation.

    Genomics 1991;10;1;157-65

  • Localisation of neurone-specific enolase (ENO2) to 12p13.

    Craig SP, Day IN, Thompson RJ and Craig IW

    Biochemistry Department, University of Oxford, UK.

    We have localised the human cDNA for neurone-specific enolase (ENO2) to chromosome region 12p13 by in situ hybridisation. Two additional smaller peaks of hybridisation to specific chromosomal subregions were observed. That on chromosome 1p36 probably represents cross-hybridisation to the locus for nonneuronal enolase (ENO1), which has been previously localised to this chromosome and with which ENO2 shares homology. A further gene for a member of the enolase family may be responsible for the hybridisation to chromosome 17.

    Funded by: Wellcome Trust

    Cytogenetics and cell genetics 1990;54;1-2;71-3

  • Cloning, expression and sequence homologies of cDNA for human gamma enolase.

    Oliva D, Barba G, Barbieri G, Giallongo A and Feo S

    Istituto di Biologia dello Sviluppo (Consiglio Nazionale delle Ricerche), Palermo, Italy.

    The nucleotide sequence of the human gamma-enolase mRNA was determined from recombinant cDNA clones. The sequence spans 2273 bp and includes the complete coding region of 1299 bp, a 5'-noncoding region of 74 bp and a 897-bp-long 3'-noncoding region containing a variant polyadenylation signal (ATTAAA). The deduced amino acid (aa) sequence is 433 aa long and shows a 97% similarity with rat gamma-enolase. Both the 5'- and 3'-untranslated regions are similar (82% and 68%, respectively) to the analogous regions of the rat gamma-enolase gene, suggesting that a strong selective pressure operates on noncoding segments of gamma-enolase mRNAs. The size of the gamma-enolase mRNA expressed in human brain is 2.4 kb. A crosshybridizing 1.5-kb message is detected in human skeletal muscle which may be derived from the beta-enolase-coding gene.

    Gene 1989;79;2;355-60

  • Complete amino acid sequence of the neurone-specific gamma isozyme of enolase (NSE) from human brain and comparison with the non-neuronal alpha form (NNE).

    McAleese SM, Dunbar B, Fothergill JE, Hinks LJ and Day IN

    Department of Biochemistry, University of Aberdeen, Marischal College, Scotland.

    The complete amino acid sequence (433 residues) of the human neurone-specific gamma isozyme of enolase (NSE) has been determined by a combination of direct amino acid sequencing and nucleotide sequencing of cloned cDNA. Substantial amino acid sequence of the non-neuronal alpha form of the enzyme was also obtained which agreed almost entirely with the indirect cDNA sequence. Comparison of the two human sequences shows no insertions or deletions, but 72 replacements. Comparison of the human gamma form with the corresponding isozyme from the rat shows only 7 replacements (compared to 27 changes between the human and rat alpha isozymes). We have identified regions of sequence difference between the human alpha and gamma forms that are mainly hydrophilic in character (residues 271-285, 298-316 and 416-433). These residues are on the surface of the three-dimensional structure and could be useful as immunogens to produce antibodies specific for the neurone-specific form.

    European journal of biochemistry 1988;178;2;413-7

  • Human gamma enolase: isolation of a cDNA clone and expression in normal and tumor tissues of human origin.

    Van Obberghen E, Kamholz J, Bishop JG, Zomzely-Neurath C, Lazzarini RA and Lazzarini RA

    Laboratory of Molecular Genetics, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.

    We have isolated and sequenced a cDNA clone encoding the human gamma enolase. Comparison of our cDNA sequence and the rat gamma enolase sequence revealed 97% homology at the level of amino acid sequence. The two coding regions were 91% homologous on the nucleotide level, whereas the 3' noncoding regions were much less homologous (32%). Further comparison of our cDNA sequence with the human alpha enolase revealed an 82% homology at the amino acid level and a 75% homology at the nucleotide level for the two coding regions, whereas the 3' nontranslated regions were only 30% homologous. Using a portion of the 3' nontranslated region of our cDNA, shown to be specific for human gamma enolase, a single 2.5 kb mRNA was detected in human brain tissue. This same gamma enolase message was also found in a number of human normal nonneuronal tissues, and in several human tumor-derived cell lines. Expression of the mRNA for the gamma enolase subunit should thus be used with caution when identifying the cells of neuronal or neuroendocrine origin.

    Journal of neuroscience research 1988;19;4;450-6

  • Sequence conservation in the 3'-untranslated regions of neurone-specific enolase, lymphokine and protooncogene mRNAs.

    Day IN, Allsopp MT, Moore DC and Thompson RJ

    Department of Clinical Biochemistry, School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, England.

    The C-terminal protein-coding and the entire 3'-untranslated regions of a cDNA corresponding to human neurone-specific enolase mRNA have been sequenced. The 3'-untranslated region is 892 bases long and shows a high degree of homology with the 3'-untranslated region of rat neurone-specific enolase mRNA. This sequence conservation is not seen in non-neuronal enolase mRNAs. Features of the conserved sequence include an A-rich region approx. 250 bases from the stop codon at a point corresponding to the polyadenylation signal site in non-neuronal enolase mRNA, and a repeating ATTT sequence. This unusual motif in eukaryotic mRNAs has previously been reported in the 3'-untranslated regions of lymphokine and protooncogene mRNAs.

    FEBS letters 1987;222;1;139-43

  • Immunohistochemical localization of gamma-enolase in normal human tissues other than nervous and neuroendocrine tissues.

    Haimoto H, Takahashi Y, Koshikawa T, Nagura H and Kato K

    The neuron-specific enolase, gamma-enolase, is present at high concentrations in tissues of the nervous and neuroendocrine systems and at significant levels in other human tissues as detected by enzyme immunoassay. Its precise localization, however, has remained unclear. We report here the immunohistochemical localization of gamma-enolase in normal adult human tissues other than those of the nervous and neuroendocrine systems using direct and indirect enzyme-labeled antibody methods. The gamma-enolase was found in such smooth muscle cells as the media of aorta, fibromuscular tissue of the prostate, and the myometrium of the uterus, myoepithelial cells, the conducting system of heart, epithelial cells of loops of Henle, and macula densa cells of the kidney. It was also demonstrated in spermatogonia, lymphocytes, plasma cells, platelets, and megakaryocytes and in lesser amounts in bronchial epithelial cells and type II alveolar epithelial cells of the lung, and in secretory cells of the fallopian tube. The significance of its presence in these cells and the application of the gamma-enolase detection for diagnostic purposes in pathology are discussed.

    Laboratory investigation; a journal of technical methods and pathology 1985;52;3;257-63

Gene lists (8)

Gene List Source Species Name Description Gene count
L00000009 G2C Homo sapiens Human PSD Human orthologues of mouse PSD adapted from Collins et al (2006) 1080
L00000011 G2C Homo sapiens Human clathrin Human orthologues of mouse clathrin coated vesicle genes adapted from Collins et al (2006) 150
L00000012 G2C Homo sapiens Human Synaptosome Human orthologues of mouse synaptosome adapted from Collins et al (2006) 152
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
L00000059 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus 748
L00000061 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-CONSENSUS Mouse cortex PSD consensus (ortho) 984
L00000069 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list 1461
L00000071 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-FULL Mouse cortex PSD full list (ortho) 1556
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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