G2Cdb::Gene report

Gene id
G00001665
Gene symbol
LDHB (HGNC)
Species
Homo sapiens
Description
lactate dehydrogenase B
Orthologue
G00000416 (Mus musculus)

Databases (8)

Curated Gene
OTTHUMG00000133760 (Vega human gene)
Gene
ENSG00000111716 (Ensembl human gene)
3945 (Entrez Gene)
113 (G2Cdb plasticity & disease)
LDHB (GeneCards)
Literature
150100 (OMIM)
Marker Symbol
HGNC:6541 (HGNC)
Protein Sequence
P07195 (UniProt)

Literature (29)

Pubmed - other

  • Molecular risk stratification of medulloblastoma patients based on immunohistochemical analysis of MYC, LDHB, and CCNB1 expression.

    de Haas T, Hasselt N, Troost D, Caron H, Popovic M, Zadravec-Zaletel L, Grajkowska W, Perek M, Osterheld MC, Ellison D, Baas F, Versteeg R and Kool M

    Department of Human Genetics, Neuropathology, and Neurogenetics, Academic Medical Center, Amsterdam, the Netherlands.

    Purpose: Medulloblastoma is the most common malignant embryonal brain tumor in children. The current clinical risk stratification to select treatment modalities is not optimal because it does not identify the standard-risk patients with resistant disease or the unknown number of high-risk patients who might be overtreated with current protocols. The aim of this study is to improve the risk stratification of medulloblastoma patients by using the expression of multiple prognostic markers in combination with current clinical parameters.

    Candidate prognostic markers were selected from literature or from medulloblastoma expression data. Selected genes were immunohistochemically analyzed for their prognostic value using medulloblastoma tissue arrays containing 124 well-characterized patient samples.

    Results: Protein expression analyses showed that the combined expression of three genes was able to predict survival in medulloblastoma patients. Low MYC expression identified medulloblastoma patients with a very good outcome. In contrast, concomitant expression of LDHB and CCNB1 characterized patients with a very poor outcome. Multivariate analyses showed that both expression of MYC and the LDHB/CCNB1 gene signature were strong prognostic markers independent of the clinical parameters metastasis and residual disease. Combined analysis of clinical and molecular markers enabled greater resolution of disease risk than clinical factors alone.

    Conclusions: A molecular risk stratification model for medulloblastoma patients is proposed based on the signature of MYC, LDHB, and CCNB1 expression. Combined with clinical variables, the model may provide a more accurate basis for targeting therapy in children with this disease.

    Clinical cancer research : an official journal of the American Association for Cancer Research 2008;14;13;4154-60

  • Increased serum lactate dehydrogenase isoenzymes in Ph-negative chronic myeloproliferative diseases: a metabolic adaptation?

    Mazzotta S, Guerranti R, Gozzetti A, Bucalossi A, Bocchia M, Sammassimo S, Petralia S, Ogueli GI and Lauria F

    Department of Hematology and Transplants, University of Siena, Siena, Italy. mazserena@yahoo.it

    We evaluated the significance of lactate dehydrogenase (LDH) isoenzymes in chronic myeloproliferative disorders (CMDs) by studying LDH isoenzymes in the serum of patients with secondary polycythemia (SP), polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF) in different disease status. LDH activity and isoenzymes were evaluated retrospectively in serum samples from four groups of patients and compared with a control group. LDH activity and isoenzyme distributions of patients with SP and PV did not reveal significant variations with respect to controls. In the ET and IMF group LDH isoenzyme revealed significant variations: IMF showed significant increase of LDH2 and significant reduction of LDH5 isoenzyme, whereas ET showed significant decrease in LDH1 and increase of LDH3. These data suggest that LDH isoenzyme patterns may be a useful marker of CMDs, but this enzymatic pattern could be expression of a metabolic adaptation.

    Hematology (Amsterdam, Netherlands) 2006;11;4;239-44

  • 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

  • Towards a proteome-scale map of the human protein-protein interaction network.

    Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP and Vidal M

    Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.

    Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.

    Funded by: NCI NIH HHS: R33 CA132073; NHGRI NIH HHS: P50 HG004233, R01 HG001715, RC4 HG006066, U01 HG001715; NHLBI NIH HHS: U01 HL098166

    Nature 2005;437;7062;1173-8

  • Proteomics of human umbilical vein endothelial cells applied to etoposide-induced apoptosis.

    Bruneel A, Labas V, Mailloux A, Sharma S, Royer N, Vinh J, Pernet P, Vaubourdolle M and Baudin B

    Service de Biochimie A, Hôpital Saint-Antoine, AP-HP, Paris, France. arnaud.bruneel@sat.ap-hop-paris.fr

    We have undertaken to continue the proteomic study of human umbilical vein endothelial cells (HUVECs) using the combination of 2-DE, automated trypsin digestion, and PMF analysis after MALDI-TOF MS and peptide sequencing using nano LC-ESI-MS/MS. The overall functional characterization of the 162 identified proteins from primary cultures of HUVECs confirms the metabolic capabilities of endothelium and illustrates various cellular functions more related to cell motility and angiogenesis, protein folding, anti-oxidant defenses, signal transduction, proteasome pathway and resistance to apoptosis. In comparison with controls cells, the differential proteomic analysis of HUVECs treated by the pro-apoptotic topoisomerase inhibitor etoposide further revealed the variation of eight proteins, namely, GRP78, GRP94, valosin-containing protein, proteinase inhibitor 9, cofilin, 37-kDa laminin receptor protein, bovine apolipoprotein, and tropomyosin. These data suggest that etoposide-induced apoptosis of human vascular endothelial cells results from the intricate involvement of multiple apoptosis processes including at least the mitochondrial and the ER stress pathways. The presented 2-D pattern and protein database, as well as the data related to apoptosis of HUVECs, are available at http://www.huvec.com.

    Proteomics 2005;5;15;3876-84

  • Proteomic analysis of oxidatively modified proteins induced by the mitochondrial toxin 3-nitropropionic acid in human astrocytes expressing the HIV protein tat.

    Pocernich CB, Poon HF, Boyd-Kimball D, Lynn BC, Nath A, Klein JB and Butterfield DA

    Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA; Center of Membrane Sciences, University of Kentucky, Lexington, KY 40506, USA.

    The human immunodeficiency virus (HIV)-Tat protein has been implicated in the neuropathogenesis of HIV infection. However, its role in modulating astroglial function is poorly understood. Astrocyte infection with HIV has been associated with rapid progression of dementia. Intracellularly expressed Tat is not toxic to astrocytes. In fact, intracellularly expressed Tat offers protection against oxidative stress-related toxins such as the mitochondrial toxin 3-nitroproprionic acid (3-NP). In the current study, human astrocytes expressing Tat (SVGA-Tat) and vector controls (SVGA-pcDNA) were each treated with the irreversible mitochondrial complex II inhibitor 3-NP. Proteomics analysis was utilized to identify changes in protein expression levels. By coupling 2D fingerprinting and identification of proteins by mass spectrometry, actin, heat shock protein 90, and mitochondrial single-stranded DNA binding protein were identified as proteins with increased expression, while lactate dehydrogenase had decreased protein expression levels in SVGA-Tat cells treated with 3-NP compared to SVGA-pcDNA cells treated with 3-NP. Oxidative damage can lead to several events including loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, ultimately leading to neuronal death. Identification of specific proteins protected from oxidation is a crucial step in understanding the interaction of Tat with astrocytes. In the current study, proteomics also was used to identify proteins that were specifically oxidized in SVGA-pcDNA cells treated with 3-NP compared to SVGA-Tat cells treated with 3-NP. We found beta-actin, calreticulin precursor protein, and synovial sarcoma X breakpoint 5 isoform A to have increased oxidation in control SVGA-pcDNA cells treated with 3-NP compared to SVGA-Tat cells treated with 3-NP. These results are discussed with reference to potential involvement of these proteins in HIV dementia and protection of astrocytes against oxidative stress by the HIV virus, a prerequisite for survival of a viral host cell.

    Funded by: NCRR NIH HHS: P20 RR15592; NIA NIH HHS: AG-05119, AG-10836; NIMH NIH HHS: MH64409; NINDS NIH HHS: R01 NS39253

    Brain research. Molecular brain research 2005;133;2;299-306

  • 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

  • Association of an exonic LDHA polymorphism with altered respiratory response in probands at high risk for panic disorder.

    Philibert RA, Nelson JJ, Sandhu HK, Crowe RR and Coryell WH

    Department of Psychiatry, The University of Iowa, Iowa City, Iowa 52242-1000, USA. robert-philibert@uiowa.edu

    Panic disorder (PD) is a clinical syndrome characterized by recurrent discrete episodes of fear accompanied by a variety of physiological and psychological symptoms, often with prominent respiratory components. A series of clinical observations has led some investigators to hypothesize that subtle alterations in ventilatory regulation are integral to at least a subtype of PD. In order to identify genetic factors that might predispose individuals to these alterations in ventilatory response, we conducted single stranded conformation polymorphism analysis across the exons of the lactate dehydrogenase A and B genes (LDHA and LDHB) using DNA prepared from 86 subjects previously characterized by respiratory response to a CO(2) challenge with a variable genetic loading for PD. Remarkably, a single conserved LDHA exon 5 haplotype conferred increased risk for a paradoxical ventilatory response pattern to CO(2) inhalation which robustly separated well subjects at high risk for PD from low-risk control subjects. But, comparison of LDHA exon 5 genotypes in PD probands (n = 25) to that of random newborn controls (n = 182) did not demonstrate any significant differences. Given the pivotal role of LDH in the metabolism of lactate, a known inducer of panic attacks, and the dependence of LDH activity on cell pH, we suggest that LDHA polymorphisms may contribute to the variability to CO(2) respiratory challenge.

    Funded by: NIMH NIH HHS: MH 56132

    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2003;117B;1;11-7

  • Identification of breast cancer-restricted antigens by antibody screening of SKBR3 cDNA library using a preselected patient's serum.

    Forti S, Scanlan MJ, Invernizzi A, Castiglioni F, Pupa S, Agresti R, Fontanelli R, Morelli D, Old LJ, Pupa SM and Ménard S

    Department of Experimental Oncology, Istituto Nazionale Tumori, Milano, Italy.

    Screening of a breast cancer cDNA library from SKBR3 human breast cancer cells by SEREX (serological analysis of cDNA expression library) using a preselected serum from a breast cancer patient revealed 13 genes, two of which, INT-MI-1 and INT-MI-2, encode novel gene products, while the remaining 11 genes and their products are identical with or highly homologous to known GenBank entries. Immunoscreening of the 13 clones using 20 allogeneic sera from breast cancer patients and 20 samples from age- and gender-matched healthy donors showed that lactate dehydrogenase-A (LDH-A), lactate dehydrogenase-B (LDH-B), fibulin-1, and thyroid hormone-binding protein (THBP) were recognized principally by the breast cancer patient sera, indicating the immunogenicity of these molecules in vivo. The other antigens were similarly recognized by normal and patients sera, and thus not tumor-restricted immunologically. RT-PCR analysis revealed strong expression of fibulin-1 in tumor cell lines and surgical specimen whereas in the same experimental conditions, normal tissues scored negative. Also THBP expression was found in various tumors whereas in normal tissues, its expression is restricted to the testis and, at lower levels, in ovary, liver, and spleen. In contrast, LDH-A and LDH-B were ubiquitously expressed in normal and tumor tissues, with LDH-B levels considerably lower and heterogeneous in normal samples compared to those expressed in tumor cell lines. The differential expression of fibulin-1 between the normal tissues and breast carcinoma cell lines (5/6) and surgical specimens (5/6) suggests the possible involvement of the overexpression of this extracellular matrix-associated glycoprotein in the pathogenesis of this neoplasm.

    Breast cancer research and treatment 2002;73;3;245-56

  • Protective effect of glutathione in HIV-1 lytic peptide 1-induced cell death in human neuronal cells.

    Sung JH, Shin SA, Park HK, Montelaro RC and Chong YH

    Department of Microbiology, College of Medicine, Division of Molecular Biology and Neuroscience, Medical Research Center, Ewha Womans University, Yangcheonku, Seoul, Korea.

    To elucidate the pathogenic mechanisms involved in neurodegeneration in AIDS patients with cognitive deficits, we have examined the toxic effect of the lentivirus lytic peptide 1 (LLP-1) corresponding to the carboxyl terminus of HIV-1 transmembrane glycoprotein gp41 on human neuronal and glial cell lines. LLP-1 induced a significant lactate dehydrogenase (LDH, a marker of cell death) release from these cells in a concentration- and time-dependent manner, while the noncytolytic LLP-1 analog 2 had little effect. Application of LLP-1 to SH-SY5Y, a well-characterized human neuronal cell line, caused the decline of intracellular glutathione (GSH) content that appeared to occur before a significant LDH release. Furthermore, LLP-1 elicited a significant loss of mitochondrial function as measured by mitochondrial transmembrane potential (MTP). Among the reducing agents and antioxidants tested, GSH and a GSH prodrug N-acetylcysteine (NAC) provided protection against LLP-1-induced neuronal cell death, evidently by restoring the intracellular GSH levels and blocking the disruption of mitochondrial integrity. Thus, gp41-derived LLP-1 may be a potential neurotoxic agent capable of causing the intracellular GSH depletion and disturbing the mitochondrial function, possibly contributing to the neurodegenerative cascade as seen in HIV-1-associated dementia. Our data indicate that restoring both GSH concentration and mitochondrial function may hold promise as possible therapeutic strategies for slowing disease progression of dementia in AIDS patients.

    Journal of neurovirology 2001;7;5;454-65

  • A novel missense mutation in human lactate dehydrogenase B-subunit gene.

    Takatani T, Takaoka N, Tatsumi M, Kawamoto H, Okuno Y, Morita K, Masutani T, Murakawa K and Okamoto Y

    Central Clinical Laboratory, Nara Medical University Hospital, Shijo-Cho 840, Kashihara, Nara 634-8522, Japan.

    Reduced activity of serum lactate dehydrogenase (LDH; EC 1.1.1.27) was found in a male medical student during practical examinations of his own blood. Serum LDH isoenzyme pattern showed reductions in activities of the isoenzymes with lower subunit A/B ratios such as LDH1 and LDH2. These findings were indicative of a partial LDH-B subunit deficiency, which was confirmed in erythrocyte hemolysates by Western blotting. Polymerase chain reaction (PCR)-based DNA sequence analysis of the LDH-B subunit gene revealed a heterozygous nucleotide change: a guanine to adenine substitution in codon 69 (GGG --> GAG) at the third exon of the LDH-B subunit gene that resulted in a glycine to glutamic acid substitution (G69E). The mutation was confirmed by PCR-restriction fragment length polymorphism (RFLP) analysis using a mismatched primer to introduce a new NcoI restriction site. The same heterozygous mutation was found in his mother but not in other family members. This mutation involves a residue belonging to alphaC helix in LDH-B subunit protein molecule that functions as an interface for other subunits.

    Molecular genetics and metabolism 2001;73;4;344-8

  • Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase.

    Read JA, Winter VJ, Eszes CM, Sessions RB and Brady RL

    Department of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.

    Lactate dehydrogenase (LDH) interconverts pyruvate and lactate with concomitant interconversion of NADH and NAD(+). Although crystal structures of a variety of LDH have previously been described, a notable absence has been any of the three known human forms of this glycolytic enzyme. We have now determined the crystal structures of two isoforms of human LDH-the M form, predominantly found in muscle; and the H form, found mainly in cardiac muscle. Both structures have been crystallized as ternary complexes in the presence of the NADH cofactor and oxamate, a substrate-like inhibitor. Although each of these isoforms has different kinetic properties, the domain structure, subunit association, and active-site regions are indistinguishable between the two structures. The pK(a) that governs the K(M) for pyruvate for the two isozymes is found to differ by about 0.94 pH units, consistent with variation in pK(a) of the active-site histidine. The close similarity of these crystal structures suggests the distinctive activity of these enzyme isoforms is likely to result directly from variation of charged surface residues peripheral to the active site, a hypothesis supported by electrostatic calculations based on each structure. Proteins 2001;43:175-185.

    Proteins 2001;43;2;175-85

  • Direct role of plasma membrane-expressed gp120/41 in toxicity to human astrocytes induced by HIV-1-infected macrophages.

    Boutet A, Altmeyer R, Héry C and Tardieu M

    Laboratoire Virus, Neurone et Immunité, Université Paris-Sud, Le Kremlin-Bicêtre, France. agnes.boutet@kb.u-psud.fr

    Objective: To compare astrocyte toxicity induced by plasma membrane-expressed gp120/41 and soluble gp120.

    Design: Analysis of morphological alterations and lactate dehydrogenase (LDH) release from astrocytes in culture with monocytes infected with HIV-1, microglia expressing Env of a macrophage-tropic HIV-1 isolate or soluble Env.

    Methods: Primary human embryonic astrocytes were cultured with: monocytes infected with two M-tropic HIV-1 isolates (HIV-1(9533), HIV-1(BX08)); human microglia infected with the defective Semliki Forest virus (SFV) vector coding for the env gene of HIV-1(BX08) isolate (SFVenvBX08); and soluble gp140 purified from baby hamster kidney cells transfected with the env gene of HIV-1(BX08) lacking the intracytoplasmic region of gp41 (SFVdelta envBX08). Gp120 mRNA levels were assessed by quantitative reverse transcriptase-polymerase chain reaction and the protein was detected by immunofluorescence in infected monocytes or microglia.

    Results: Contact of HIV-infected monocytes induced morphological changes in astrocytes and a 137% increase in LDH release at day 2 of co-culture compared with controls (uninfected monocytes). Gp120/41(BX08)-expressing microglia induced a 170% increase in LDH release (relative to SFVLacZ-infected microglia). Pretreatment of co-cultures with an anti-gp120 monoclonal antibody (mAb; NEA-9305) directed against the V3 loop inhibited LDH release. Soluble purified gp140 from BX08 isolate induced only a weak LDH release (104%). Finally, cytotoxicity was not blocked by treatment of the co-culture with Bordetella pertussis toxin, an inhibitor of Gi alpha protein-dependent receptors.

    Conclusion: HIV envelope glycoprotein expressed at the plasma membrane induced astrocyte damage more efficiently than its soluble counterpart. The V3 loop was involved in toxicity induction through a pathway independent of the Gi alpha protein-coupled receptor.

    AIDS (London, England) 2000;14;17;2687-97

  • Antigens recognized by autologous antibody in patients with renal-cell carcinoma.

    Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jäger D, Jäger E, Knuth A, Chen YT and Old LJ

    Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. scanlanm@mskcc.org

    The screening of cDNA expression libraries derived from human tumors with autologous antibody (SEREX) is a powerful method for defining the structure of tumor antigens recognized by the humoral immune system. Sixty-five distinct antigens (NY-REN-1 to NY-REN-65) reactive with autologous IgG were identified by SEREX analysis of 4 renal cancer patients and were characterized in terms of cDNA sequence, mRNA expression pattern, and reactivity with allogeneic sera. REN-9, -10, -19, and -26 have a known association with human cancer. REN-9 (LUCA-15) and REN-10 (gene 21) map to the small cell lung cancer tumor suppressor gene locus on chromosome 3p21.3. REN-19 is equivalent to LKB1/STK11, a gene that is defective in Peutz-Jeghers syndrome and cancer. REN-26 is encoded by the bcr gene involved in the [t(9:22)] bcr/abl translocation. Genes encoding 3 of the antigens in the series showed differential mRNA expression; REN-3 displays a pattern of tissue-specific isoforms, and REN-21 and REN-43 are expressed at a high level in testis in comparison to 15 other normal tissues. The other 62 antigens were broadly expressed in normal tissues. With regard to immunogenicity, 20 of the 65 antigens reacted only with autologous sera. Thirty-three antigens reacted with sera from normal donors, indicating that their immunogenicity is not restricted to cancer. The remaining 12 antigens reacted with sera from 5-25% of the cancer patients but not with sera from normal donors. Seventy percent of the renal cancer patients had antibodies directed against one or more of these 12 antigens. Our results demonstrate the potential of the SEREX approach for the analysis of the humoral immune response against human cancer.

    International journal of cancer 1999;83;4;456-64

  • Genetic analyses in homozygous and heterozygous variants of lactate dehydrogenase-B (H) subunit--LD-B Matsumoto I and II (LD-B W323R).

    Okumura N, Terasawa F, Ueno I, Oki K, Yamauchi K, Hidaka H, Tozuka M, Okura M and Katsuyama T

    Department of Medical Technology, School of Allied Medical Sciences, Shinshu University, Matsumoto, Japan. nobuoku@gipac.shinshu-u.ac.jp

    Clinica chimica acta; international journal of clinical chemistry 1999;287;1-2;163-71

  • A novel in-frame deletion mutation in a case of lactate dehydrogenase (LD) H subunit deficiency showing an atypical LD isoenzyme pattern in serum and erythrocytes.

    Sudo K, Maekawa M, Houki N, Okuda T, Akizuki S, Magara T and Kawano K

    Department of Laboratory Medicine, Jikei University, Daisan Hospital, Komae City, Tokyo, Japan. kayosudo@jikei.ac.jp

    Objective: We report a case showing an atypical lactate dehydrogenase (LD) isoenzyme pattern involving deficiency only of LD-1 and LD-2 in serum and erythrocytes. LD activity in serum from this patient was extremely low, similar to complete LD-H deficiency, and also that in erythrocytes was low.

    Design: The DNA fragment containing exon 1 through 7 of the LD-H gene were amplified by PCR and directly sequenced. Total RNA was prepared from venous blood and the proportion of LD-H cDNA to total LD cDNA was semiquantified.

    Results: Genetic analysis by DNA sequencing detected a three base deletion (AAT) at codon 220 of exon 5, which caused a deletion of one asparagine. The present case did not show reduced LD-H expression at the mRNA level in whole blood. Residue 220 is involved in turning beta-J to alpha1-G and is not buried in the interior of the protein. The novel homozygous in-frame deletion mutation at codon 220 may cause a three-dimensional change of the subunit-binding domain.

    Clinical biochemistry 1999;32;2;137-41

  • First case of missense mutation (LDH-H:R171P) in exon 4 of the lactate dehydrogenase gene detected in a Japanese patient.

    Hidaka K, Ueda N, Hirata I, Watanabe Y, Minatogawa Y and Iuchi I

    Department of Biochemistry, Kawasaki Medical School, Kurashiki, Japan. kazuohi@med.kawasaki-m.ac.jp

    Complete deficiency of lactate dehydrogenase (LDH) subunit H was identified in a 41-year-old woman with paralysis of her left lower limb. The propositus had extremely low LDH activity and five of her family members had levels of LDH activity that ranged from lower than normal to normal level. A transversion mutation at codon 171 (CGC-->CCC), resulting in an Arg-->Pro substitution was identified in her DNA sequence. A new NruI restriction site was introduced into the polymerase chain reaction (PCR) product by PCR-primer introduced restriction analysis (PCR-PIRA) using a specific mismatched primer. Digestion with NruI revealed that the propositus and her mother were, respectively, homozygous and heterozygous for this mutation.

    Journal of human genetics 1999;44;1;69-72

  • Arginine to tryptophan substitution in the active site of a human lactate dehydrogenase variant--LDHB GUA1: postulated effects on subunit structure and catalysis.

    Shonnard GC, Hud NV and Mohrenweiser HW

    Biology and Biotechonology Research Program, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.

    A variant of lactate dehydrogenase (LDHB GUA1) was previously identified among the Guaymi Indians of Panama and Costa Rica. The LDHB GUA1 variant is enzymatically inactive; however, the variant subunits alter the electrophoretic mobility of the tetramers that include active LDHA and LDHB subunits. The kinetic properties of the tetrameric enzyme, comprised of the inactive B plus active A subunits, are similar to properties of the heterotetramers with active B subunits, except for the reduced specific activity. We have determined that a single C.G to T.A transition changes an Arg to a Trp at amino acid residue 106. This substitution explains the increase in net negative charge observed by protein electrophoresis. This Arg 106 residue is absolutely conserved throughout evolution. Published high-resolution crystal structures of LDH reveal that this residue is within the hinge of a loop that closes over the active site of the subunit upon binding of substrate and cofactor and also has a direct role in catalysis. Computer modeling of the variant enzyme suggests that replacement of this Arg residue with a Trp does not induce significant change in the structure of the active site. However, this substitution would result in disruption of enzyme activity through the inability of the uncharged tryptophan side-chain to polarize the substrate carbonyl bond. This would explain the loss of the catalytic function with maintenance of normal kinetic properties in the heterotetramers containing the variant subunits. The ability to maintain normal, tissue-specific kinetic properties could explain the absence of clinical manifestations in the homozygous LDHB GUA1 individuals.

    Biochimica et biophysica acta 1996;1315;1;9-14

  • Analysis of a genetic mutation in an electrophoretic variant of the human lactate dehydrogenase-B(H) subunit.

    Maekawa M, Sudo K, Kitajima M, Matsuura Y, Li SS and Kanno T

    Department of Laboratory Medicine, Hamamatsu University School of Medicine, Japan.

    An electrophoretic variant of the lactate dehydrogenase (LDH)-B(H) subunit was discovered in a patient with diabetes mellitus. His LDH activity in serum was slightly lower than normal and the LDH isozyme pattern showed an abnormal migration indicating an LDH-B subunit variant of the fast type. The LDH containing the variant subunit revealed a decreased heat stability. DNA analysis of the variant allele detected a base substitution, an A to G transition, at codon 6 (AAA-->GAA). The mutation resulted in the replacement of a lysine by a glutamic acid (K6E). The change may cause the heat instability and affect the net charge of the variant subunit, resulting in an electrophoretic LDH-B subunit variant of the fast type.

    Human genetics 1993;91;5;423-6

  • Detection and characterization of new genetic mutations in individuals heterozygous for lactate dehydrogenase-B(H) deficiency using DNA conformation polymorphism analysis and silver staining.

    Maekawa M, Sudo K, Kitajima M, Matsuura Y, Li SS and Kanno T

    Department of Laboratory Medicine, Hamamatsu University School of Medicine, Japan.

    Human lactate dehydrogenase (LDH)--B(H) mutant genes were analyzed by polymerase chain reaction (PCR) and DNA conformation polymorphism. We used polyacrylamide gradient gel and silver staining procedures for DCP analysis, and observed abnormal migration patterns in individuals heterozygous for the LDH-B deficiency. Subsequent sequence determination of the mutant alleles consistently resulted in detection of three single base substitutions (transversions), viz., a C to A at residue "35" (GCG, Ala-->GAG, Glu), a T to G at residue "172" (TTT, Phe-->GTT, Val), and an A to T at residue "176" (ATG, Met-->TTG, Leu). Furthermore, mismatched PCR or amplification refractory mutation system was developed for the rapid screening and confirmation of these mutations. These amino acid replacements may cause conformational changes in neighboring residues; this probably affects the active site arrangement and results in the loss of enzyme activity.

    Human genetics 1993;91;2;163-8

  • Molecular characterization of genetic mutations in human lactate dehydrogenase (LDH) B (H) variant.

    Sudo K, Maekawa M, Tomonaga A, Tsukada T, Nakayama T, Kitamura M, Li SS, Kanno T and Toriumi J

    Department of Laboratory Medicine, Jikei University School of Medicine, Daisan Hospital, Komae, Japan.

    We have previously detected a single base substitution of G by A at the Arg codon CGC in exon 4 of the mutant lactate dehydrogenase (LDH) gene, an unstable LDH-B variant (case 1). Here, we use the polymerase chain reaction (PCR) to amplify genomic DNA of two cases (the original case 1 and a new patient, case 2). We were able to confirm that case 1 is homozygous for the mutation, causing a replacement of the conserved Arg by His at residue 173. The resulting LDH-B variant subunit is unstable in vivo. Whereas the mutation in exon 4 was not observed in case 2, a different single base substitution of A by C was detected at the Ser codon AGT in exon 3. This mutation causes a replacement of the conserved Ser by Arg at residue 131. Genomic analysis of the family of case 2 by mismatched PCR showed that the missense mutation was consistent with their biochemical phenotypes. The replacement results in a conformational change of the residues near the Ser, probably because the side chain of Arg is much more bulky than that of Ser. The change may affect the arrangement of the cofactor binding site and result in the loss of enzyme activity. The experimental observations are consistent with computer graphics analyses.

    Human genetics 1992;89;2;158-62

  • Human centrosomal epitope is shared specifically with human lactate dehydrogenase-B isozyme.

    Gosti F, Li SS, Maunoury R and Bornens M

    Centre de Génétique Moléculaire, CNRS, Gif-sur-Yvette, France.

    A rabbit serum (0013) used to identify pericentriolar proteins from isolated centrosomes (Gosti-Testu, F., Marty, M.C., Berges, J., Maunoury, R. and Bornens, M. (1986) EMBO J. 5, 2545-2550) was shown also to react through the same epitope with several non-centrosomal proteins including a major 36 kDa cytosolic antigen. This protein was identified to be human lactate dehydrogenase and the co-distribution of 0013 epitope on the centrosomal protein and on lactate dehydrogenase (LDH) was shown to be specific for human cells (Gosti, F., Marty, M.C., Courvalin, J.C., Maunoury, R. and Bornens, M. (1987) Proc. Natl. Acad. Sci. USA 84, 1000-1004). Human hepatic cells constitute, so far, the only exception to this co-distribution rule. By using this cell type which expresses only the LDH-A4 isozyme, we demonstrate that 0013 epitope is specific for the human LDH-B subunit, making serum 0013 the strongest anti-LDH-B available so far. The evolutionary and physiological significance of this situation is discussed.

    FEBS letters 1992;299;3;231-4

  • A missense mutation found in human lactate dehydrogenase-B (H) variant gene.

    Sudo K, Maekawa M, Ikawa S, Machida K, Kitamura M and Li SS

    Laboratory of Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.

    A human lactate dehydrogenase-B mutant gene was isolated from a genomic DNA library constructed from a patient with unstable LDH-B (heart) subunit. The nucleotide sequences of seven protein-coding exons were determined and a single nucleotide substitution of G by A at Arg codon CGC in exon 4 was found. This mutation results in an amino-acid replacement of a conserved arginine by histidine at the residue "173," which is involved in an anion-binding site at the P-axis of LDH subunits.

    Biochemical and biophysical research communications 1990;168;2;672-6

  • Structure of the human lactate dehydrogenase B gene.

    Takeno T and Li SS

    Laboratory of Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.

    Human genomic clones containing parts of the lactate dehydrogenase B (LDH-B) gene (approx. 25 kb in length) were isolated and characterized. The protein-coding sequence of human LDH-B gene is interrupted by six introns at codons nos. 42-43, 82, 140, 198, 237 and 278-279, and the positions of these introns are homologous to those of LDH-A genes from man and mouse. The 5' non-coding region of human LDH-B gene is interrupted by an intron six nucleotide residues upstream of the ATG translation-initiation site, whereas those of human and mouse LDH-A genes are interrupted at 24 nucleotide residues 5' to the ATG initiation codon. As is the case of LDH-A genes from man and mouse, there is no intron in the 3' non-coding region of human LDH-B gene.

    The Biochemical journal 1989;257;3;921-4

  • The cDNA and protein sequences of human lactate dehydrogenase B.

    Sakai I, Sharief FS, Pan YC and Li SS

    Laboratory of Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.

    Human lactate dehydrogenase B (LDH-B) cDNA was isolated and sequenced. The LDH-B cDNA insert consists of the protein-coding sequence (999 bp), the 5' (54 bp) and 3' (203 bp) non-coding regions, and the poly(A) tail (50 bp). The predicted sequence of 333 amino acid residues was confirmed by amino acid composition and/or sequence analyses of a total of 185 (56%) residues from tryptic peptides of human LDH-B protein. The nucleotide and amino acid sequences of the human LDH-B coding region show 68% and 75% homologies respectively with those of the human LDH-A. The peptide map and amino acid composition data have been deposited as Supplementary Publication SUP 50139 (7 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies are available on prepayment [see Biochem. J. (1987) 241, 5].

    The Biochemical journal 1987;248;3;933-6

  • The glucose-lactic acid cycle and gluconeogenesis.

    Cori CF

    Current topics in cellular regulation 1981;18;377-87

  • [Increase of the LDH-B activity in a boy with 12p trisomy by malsegregation of a maternal translocation t(12;14) (q12;p11)].

    Rethoré MO, Kaplan JC, Junien C, Cruveiller J, Dutrillaux B, Aurias A, Carpentier S, Lafourcade J and Lejeune

    A newborn male trisomic for 12p is compared with three other 12p trisomics already reported in the literature, as well as with three patients monosomic for 12p. A "type and countertype" opposition is observed for five characters: in the trisomy, turricephaly, shortness of the nose, protruding anthelix, wide palms, and increased LDH-B activity; in the monosomy, protruding occiput, large nose, hypoplasia of the anthelix, narrow palms, and decreased LDH-B activity.

    Annales de genetique 1975;18;2;81-7

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
L00000015 G2C Homo sapiens Human NRC Human orthologues of mouse NRC adapted from Collins et al (2006) 186
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
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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