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Gene Review

Ldha  -  lactate dehydrogenase A

Rattus norvegicus

Synonyms: L-lactate dehydrogenase A chain, LDH muscle subunit, LDH-A, LDH-M, Ldh-1, ...
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Disease relevance of Ldha

  • In rat C6 glioma cells, post-transcriptional gene regulation occurs through PKA-mediated stabilization of LDH-A mRNA and subsequent increase of intracellular LDH-A mRNA levels [1].
  • LDH-5, which contains only the LDH A subunit, is known to be present in both the cytoplasm and the nucleus, to act as a single-stranded DNA-binding protein possibly functioning in transcription and/or replication, and to undergo phosphorylation of tyrosine 238 in approximately 1% of the enzyme after cell transformation by certain tumor viruses [2].
  • Expression of lactate dehydrogenase A and B genes in different tissues of rats adapted to chronic hypobaric hypoxia [3].
  • During the development of hydrocephalus, lactate and LDH increased in most regions, the LDH M-subunit increased in the cortex, and ICDH decreased in most regions [4].

High impact information on Ldha

  • Although lactate did not stimulate insulin secretion from control or MCT-1-overexpressing islets, co-overexpression of LDH-A and MCT-1 evoked lactate-stimulated insulin secretion with a concomitant increase in lactate oxidation in rat islets [5].
  • In this study the significance of these characteristics was explored by overexpressing type A LDH (LDH-A) and/or type 1 MCT (MCT-1) in the clonal INS-1 beta cells and isolated rat islets [5].
  • Three fish LDH-As, as well as a single LDH of lamprey, also seem to be more related to vertebrate LDH-B than to land vertebrate LDH-A [6].
  • These seven newly deduced amino acid sequences and 22 other published LDH sequences, and three unpublished fish LDH-A sequences kindly provided by G [6].
  • The element is of dyad symmetry, consisting of a palindromic sequence with two half-sites, 5'-TCTTG-3'. It represses the expression of an LDH A/chloramphenicol acetyltransferase (CAT) reporter gene in a dose-dependent, orientation- and position-independent fashion, suggesting that it is a true silencer element [7].

Chemical compound and disease context of Ldha


Biological context of Ldha

  • Depletion of PKA subunits and AKAP 95 from RSW extracts by immunoprecipitation resulted in a marked loss of mRNA stabilization activity indicating that the presence of the PKA regulatory and catalytic subunits as well as AKAP 95 in the CSR-protein complexes was absolutely necessary to achieve LDH-A mRNA stabilization [1].
  • To determine whether formation of CSR complexes that included C, RII, and AKAP 95 constituted a functional event and was necessary for mRNA stabilization, cell-free decay reactions were carried out with RSW extracts, and the kinetics of decay of LDH-A mRNA was determined [1].
  • Structural determinants for post-transcriptional stabilization of lactate dehydrogenase A mRNA by the protein kinase C signal pathway [10].
  • In rat C6 glioma cells, LDH-A mRNA is stabilized by activation and synergistic interaction of protein kinases A and C. In the present study, we aimed to identify the sequence domain which determines and regulates mRNA stability/instability by protein kinase A and focused our attention on the 3'-untranslated region (3'-UTR) of LDH-A mRNA [11].
  • Similar effects were observed after transfection and transcription of a globin/lactate dehydrogenase minigene consisting of a beta-globin expression vector in which the 3'-untranslated region (UTR) of beta-globin had been replaced with the LDH-A 3'-UTR [10].

Anatomical context of Ldha


Associations of Ldha with chemical compounds

  • The cyclic AMP (cAMP)-inducible promoter from the rat lactate dehydrogenase A subunit gene (LDH A) is associated with a distal negative regulatory element (LDH-NRE) that represses inherent basal and cAMP-inducible promoter activity [7].
  • By each method, the half-life of relatively short-lived LDH A mRNA was increased 5- to 7-fold in 8- (4-chloro-phenylthio) cAMP or forskolin-treated and about 3-fold in 12-0-tetradecanoylphorbol-13- acetate (TPA) or dioctanoylglycerol-treated cells [15].
  • A reversion of M/H ratio of the isoenzyme pattern could be proved cytochemically by means of urea inhibition that inactivates the LDH M-subunit [16].
  • In summary, the results presented herein show that glucose transport, LDH activity and GLUT1 and LDH A mRNA levels are regulated by bFGF to achieve an increase in lactate production [13].
  • The decrease in LDHA mRNA levels (to 64 +/- 9% of the control, P<0.05) was observed with the lowest dose (2 mg/kg per day) of flutamide tested [17].

Regulatory relationships of Ldha


Other interactions of Ldha

  • Recently, the increased susceptibility to stress-induced apoptosis associated with Myc transfection has been linked to the overexpression of the LDH-A gene [19].
  • These data demonstrate that Bcl-2 overexpression reduces the Y(L/G) in Rat1-Myc cells, perhaps via a reduction in the activity or expression of the LDH-A gene, and this reduction may desensitize cells to some pro-apoptotic stimuli [19].
  • Hexokinase-I, GLUT3, and lactate dehydrogenase-A and -B were ubiquitous, whereas GLUT2, monocarboxylate transporters-1 and -2, and leptin receptor and GAD mRNAs were expressed less frequently and without apparent relationship to glucosensing capacity [20].
  • The relatively rapid basal decay rate of LDH A mRNA was also considerably slowed in the presence of the protein phosphatase inhibitor okadaic acid, suggesting a functional role for protein phosphorylation in the stabilization process [15].
  • LDH-B mRNA increased to control levels in retinal cells exposed to hypoxia then reperfused with oxygen, while the opposite was true for LDH-A, an hypoxia inducible gene [21].

Analytical, diagnostic and therapeutic context of Ldha


  1. Cyclic AMP and AKAP-mediated targeting of protein kinase A regulates lactate dehydrogenase subunit A mRNA stability. Jungmann, R.A., Kiryukhina, O. J. Biol. Chem. (2005) [Pubmed]
  2. Phosphotyrosine-containing lactate dehydrogenase is restricted to the nuclei of PC12 pheochromocytoma cells. Zhong, X.H., Howard, B.D. Mol. Cell. Biol. (1990) [Pubmed]
  3. Expression of lactate dehydrogenase A and B genes in different tissues of rats adapted to chronic hypobaric hypoxia. Rossignol, F., Solares, M., Balanza, E., Coudert, J., Clottes, E. J. Cell. Biochem. (2003) [Pubmed]
  4. Glucose metabolism and protective biochemical mechanisms in a rat brain affected by kaolin-induced hydrocephalus. Hidaka, M., Matsumae, M., Yamamura, M., Tsugane, R., Sato, O. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery. (1997) [Pubmed]
  5. Overexpression of monocarboxylate transporter and lactate dehydrogenase alters insulin secretory responses to pyruvate and lactate in beta cells. Ishihara, H., Wang, H., Drewes, L.R., Wollheim, C.B. J. Clin. Invest. (1999) [Pubmed]
  6. Evolutionary relationships of lactate dehydrogenases (LDHs) from mammals, birds, an amphibian, fish, barley, and bacteria: LDH cDNA sequences from Xenopus, pig, and rat. Tsuji, S., Qureshi, M.A., Hou, E.W., Fitch, W.M., Li, S.S. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  7. Identification of a silencer module which selectively represses cyclic AMP-responsive element-dependent gene expression. Chung, K.C., Huang, D., Chen, Y., Short, S., Short, M.L., Zhang, Z., Jungmann, R.A. Mol. Cell. Biol. (1995) [Pubmed]
  8. Cyclic AMP regulation of lactate dehydrogenase. Isoproterenol and N6,O2-dibutyryl cyclic amp increase the rate of transcription and change the stability of lactate dehydrogenase a subunit messenger RNA in rat C6 glioma cells. Jungmann, R.A., Kelley, D.C., Miles, M.F., Milkowski, D.M. J. Biol. Chem. (1983) [Pubmed]
  9. Transcriptional regulation of the lactate dehydrogenase A subunit gene by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Huang, D., Jungmann, R.A. Mol. Cell. Endocrinol. (1995) [Pubmed]
  10. Structural determinants for post-transcriptional stabilization of lactate dehydrogenase A mRNA by the protein kinase C signal pathway. Short, S., Tian, D., Short, M.L., Jungmann, R.A. J. Biol. Chem. (2000) [Pubmed]
  11. Protein kinase A-regulated instability site in the 3'-untranslated region of lactate dehydrogenase-A subunit mRNA. Tian, D., Huang, D., Short, S., Short, M.L., Jungmann, R.A. J. Biol. Chem. (1998) [Pubmed]
  12. Lactate dehydrogenase expression at the onset of altered loading in rat soleus muscle. Washington, T.A., Reecy, J.M., Thompson, R.W., Lowe, L.L., McClung, J.M., Carson, J.A. J. Appl. Physiol. (2004) [Pubmed]
  13. Regulation of lactate production and glucose transport as well as of glucose transporter 1 and lactate dehydrogenase A mRNA levels by basic fibroblast growth factor in rat Sertoli cells. Riera, M.F., Meroni, S.B., Schteingart, H.F., Pellizzari, E.H., Cigorraga, S.B. J. Endocrinol. (2002) [Pubmed]
  14. Carbon disulfide exposure attenuates adrenergic inotropic response in rats. Klapperstück, M., Müller, S., Hoffmann, P. Journal of hygiene, epidemiology, microbiology, and immunology. (1991) [Pubmed]
  15. Lactate dehydrogenase A subunit messenger RNA stability is synergistically regulated via the protein kinase A and C signal transduction pathways. Huang, D., Hubbard, C.J., Jungmann, R.A. Mol. Endocrinol. (1995) [Pubmed]
  16. Cytochemical studies of LDH isoenzymes in experimental bladder tumors. Fujii, M., Mori, H., Kato, K., Takahashi, M. J. Urol. (1982) [Pubmed]
  17. Alteration of lactate production and transport in the adult rat testis exposed in utero to flutamide. Goddard, I., Florin, A., Mauduit, C., Tabone, E., Contard, P., Bars, R., Chuzel, F., Benahmed, M. Mol. Cell. Endocrinol. (2003) [Pubmed]
  18. Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. Osthus, R.C., Shim, H., Kim, S., Li, Q., Reddy, R., Mukherjee, M., Xu, Y., Wonsey, D., Lee, L.A., Dang, C.V. J. Biol. Chem. (2000) [Pubmed]
  19. Change in lactate production in Myc-transformed cells precedes apoptosis and can be inhibited by Bcl-2 overexpression. Papas, K.K., Sun, L., Roos, E.S., Gounarides, J.S., Shapiro, M., Nalin, C.M. FEBS Lett. (1999) [Pubmed]
  20. Physiological and molecular characteristics of rat hypothalamic ventromedial nucleus glucosensing neurons. Kang, L., Routh, V.H., Kuzhikandathil, E.V., Gaspers, L.D., Levin, B.E. Diabetes (2004) [Pubmed]
  21. Hypoxic repression of lactate dehydrogenase-B in retina. Buono, R.J., Lang, R.K. Exp. Eye Res. (1999) [Pubmed]
  22. Purification and radioimmunoassay of rat lactate dehydrogenase A and B subunits. Beebee, T.J., Carty, D.S. Biochem. J. (1982) [Pubmed]
  23. Novel CRE-binding proteins of 11-16 kDa bind to the LDH A-gene CRE in a sequence specific and hepatocyte-growth dependent manner in partially hepatectomized rat liver. Lee, M.Y., Hwang, E.S., Lee, S.K. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
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