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• These seven newly deduced amino acid sequences and 22 other published LDH sequences, and three unpublished fish LDH-A sequences kindly provided by G [6].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

• The mechanism of isoproterenol and N6,O2-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cAMP) induction of lactate dehydrogenase A subunit mRNA (mRNALDH) was investigated in the rat C6 glioma cell line [8].
• Activators of protein kinase C, such as tetradecanoylphorbol acetate (TPA) and dioctanoylglycerol (DG), caused a 3-4-fold accumulation of LDH A subunit mRNA in rat C6 glioma cells [9].

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

• The mammalian LDH-C (testis) subunit appears to have diverged very early, prior to the divergence of vertebrate LDH-A and LDH-B subunits, as reported previously [6].
• In summary, the onset of altered loading induced a differential expression of LDH-A and -B in the rat soleus muscle, favoring rapid energy production [12].
• Additionally, LDH-A activity increased by 234% following 3 days of hindlimb suspension [12].
• 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 [13].
• Activity of LDH-isozymes in the myocardium was shifted toward LDH-M [14].

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

• We previously observed that the c-Myc oncogenic transcription factor regulates lactate dehydrogenase A and induces lactate overproduction [18].

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

• Purification and radioimmunoassay of rat lactate dehydrogenase A and B subunits [22].
• Such a decrease is concurrent to a decrease in lactate dehydrogenase A (LDHA) mRNA levels (evaluated through semiquantitative RT-PCR) and LDHA4 activity [17].
• We examined cAMP response element (CRE)-binding proteins involved in lactate dehydrogenase A (LDHA)-gene transcription in rat liver after partial hepatectomy [23].
• Primary retinal cultures of rat and chick were subjected to hypoxia and reperfusion paradigms, and levels of LDH-A and LDH-B mRNA expression were measured by Northern and semi-quantitative RT/PCR analyses [21].

References