Disease relevance of GAPD

• We determined first that hyperglycemia induced a decrease in glyceraldehyde-3-phosphate dehydrogenase activity in bovine aortic endothelial cells via increased production of mitochondrial superoxide and a concomitant 2.4-fold increase in hexosamine pathway activity [1].
• Regulation of endothelial cell glyceraldehyde-3-phosphate dehydrogenase expression by hypoxia [2].
• The gap gene of Staphylococcus aureus, encoding glyceraldehyde-3-phosphate dehydrogenase, was used as a target to amplify a 933-bp DNA fragment by PCR with a pair of primers 26 and 25 nucleotides in length [3].
• We isolated and identified two genes encoding proteins with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity from a S. aureus strain isolated from bovine clinical mastitis [4].
• Hyperinsulinemia reduced GAPDH expression in both states, and cyclophilin expression in early lactation [5].

High impact information on GAPD

• In this report, we show that hyperglycemia-induced overproduction of superoxide by the mitochondrial electron transport chain activates the three major pathways of hyperglycemic damage found in aortic endothelial cells by inhibiting GAPDH activity [6].
• Anti-TnT antibodies were found to be unreactive with 1) skeletal and nonmuscle isoforms of glyceraldehyde-3-phosphate dehydrogenase, a glycolytic enzyme that shares some structural homologies with skeletal TnT, and 2) calponin, a TnT-like calmodulin/tropomyosin binding protein with some antigenic properties in common with TnT [7].
• In contrast, oxidations of cysteinyl side chains in proteins, where disulfide bond formation can be prevented and where the reactivity of the nascent cysteine-sulfenic acid (Cys-SOH) can be controlled, have previously been shown to yield stable active-site Cys-SOH derivatives of papain and glyceraldehyde-3-phosphate dehydrogenase [8].
• A plasma membrane preparation of Ehrlich cells, mainly consisting of vesicles, showed the presence of 3-phosphoglycerate kinase but the absence of glyceraldehyde 3-phosphate dehydrogenase [9].
• Eighty percent of this surface-located 3-phosphoglycerate kinase was released into the assay medium during incubation, while the release of glyceraldehyde 3-phosphate dehydrogenase, at the same time, was minimal [9].

Chemical compound and disease context of GAPD

• GAPDH was induced in cells by the transition metals cobalt, nickel, and manganese and by deferoxamine, and GAPDH mRNA induction by hypoxia was blocked by cycloheximide [10].
• GAPDH induction by hypoxia, unlike that of other hypoxia-regulated genes, was not inhibited by CO or by 4,6-dioxoheptanoic acid, an inhibitor of heme synthesis [10].
• GAPDH induction by hypoxia or transitional metals was partially blocked by sodium nitroprusside but was not altered by the inhibitor of nitric oxide synthase N omega-nitro-L-arginine [10].
• To define the mechanisms by which GAPDH is regulated by hypoxia, EC were exposed to cobalt, other transition metals, carbon monoxide (CO), deferoxamine, or cycloheximide in the presence or absence of hypoxia for 24 h, and GAPDH protein and mRNA levels were measured [10].

Biological context of GAPD

• Glyceraldehyde-3-phosphate dehydrogenase is a GABAA receptor kinase linking glycolysis to neuronal inhibition [11].
• The prevention of rundown by G3P was abolished by iodoacetamide, an inhibitor of the dehydrogenase activity of GAPDH, indicating that the GABA(A) responses are maintained by a glycolysis-dependent phosphorylation [11].
• The finding that glyceraldehyde-3-phosphate dehydrogenase is present in large quantities in rod outer segments suggests that at least some of the energy required for the synthesis of ATP and GTP for phototransduction and other processes of the outer segment is derived from glycolysis which takes place within this organelle [12].
• However, unlike SMA expression, upregulation of GAPDH expression mediated by cholinergic receptor activation appeared to be insensitive to the mechanical state of airway smooth muscle [13].
• Employing reverse transcription polymerase chain reaction (RT-PCR) we investigated mRNA expression for RBP, RARalpha, RARbeta, RARgamma, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) [14].

Anatomical context of GAPD

• The GAPDH inhibitor iodoacetate suppressed GAPDH/3-PGK-dependent, but not exogenous ATP-dependent, [(3)H]glutamate uptake into isolated synaptic vesicles [15].
• Lactate dehydrogenase type-M, pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, and aldolase demonstrated the greatest amount of co-pelleting with microtubules [16].
• GAPDH and the alpha1 subunit were found to be colocalized at the neuronal plasma membrane [11].
• Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells [6].
• Protease digestion and binding studies on purified rod outer segment plasma and disk membranes suggest that glyceraldehyde-3-phosphate dehydrogenase reversibly interacts with a protease-sensitive plasma membrane-specific protein of rod outer segments [12].

Associations of GAPD with chemical compounds

• This suggests that the coupled GAPDH/3-PGK system, which converts ADP to ATP, ensures maximal glutamate accumulation into presynaptic vesicles [15].
• Interactions of the glycolytic enzymes glucose-6-phosphate isomerase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, triose-phosphate isomerase, enolase, phosphoglycerate mutase, phosphoglycerate kinase, pyruvate kinase, lactate dehydrogenase type-M, and lactate dehydrogenase type-H with tubulin and microtubules were studied [16].
• Rundown was significantly reduced by the addition of GAPDH or its reduced cofactor NADH and nearly abolished by the addition of its substrate glyceraldehyde-3-phosphate (G3P) [11].
• Molecular constructs demonstrated that GAPDH directly phosphorylates the long intracellular loop of GABA(A) receptor alpha1 subunit at identified serine and threonine residues [11].
• In bovine aortic endothelial cells, GAPDH antisense oligonucleotides activated each of the pathways of hyperglycemic vascular damage in cells cultured in 5 mM glucose to the same extent as that induced by culturing cells in 30 mM glucose [6].

Physical interactions of GAPD

• Bovine tryptophanyl-tRNA synthetase is able to form a complex with glyceraldehyde-3-phosphate dehydrogenase [17].

Other interactions of GAPD

• In most of the studies published GAPD, ACTB or 18S rRNA have been used as a single reference gene without prior verification of their expression stability [18].
• Unlike carbachol, histamine did not significantly alter the expression of GAPDH, myosin heavy chain SMA and SMB, myosin light chain LC17a and LC17b, and alpha-SM actin in bovine tracheal smooth muscle [13].
• Using a specific antibody to deplete cell extract from the molecular chaperone Hsc70, we demonstrate that this protein is required for the degradation of actin, alpha-crystallin, glyceraldehyde-3-phosphate dehydrogenase, alpha-lactalbumin, and histone H2A [19].
• Oxidative modification of protein was paralleled by loss of activity of the key metabolic enzymes, glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase [20].
• Sequence analysis of proteolytic peptides revealed the following identities: S100 beta (10 kDa), S100 alpha (11 kDa), myelin basic protein (19 kDa), glyceraldehyde-3-phosphate dehydrogenase (36 kDa) and tubulin beta-chain (50 kDa) [21].

Analytical, diagnostic and therapeutic context of GAPD

• The messenger RNA (mRNA) concentrations of beta 2-adrenergic receptors, beta ARK-I and glyceraldehyde-3-phosphate dehydrogenase (as a reference), as determined by quantitative PCR, were unaffected by fenoterol treatment [22].
• By PhosphorImaging of Northern blots, we report that the eNOS/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) messenger RNA (mRNA) ratio in bovine aortic endothelial cells (BAEC) increased by 4.8- and 7.95-fold after 6-hr shear stress exposure of 4 and 25 dynes/cm2, respectively [23].
• Effects of gestational age (GA), passage number (p), and hormonal treatment on appearance of specific mRNAs were determined by RT-PCR; relative concentrations of products determined by densitometry were analyzed as the ratio of target cDNA to the GAPDH loading control [24].
• Relative amounts of OT-NP I and glyceraldehyde-3-phosphate dehydrogenase mRNA in endometrium were assessed by reverse transcription-polymerase chain reaction and Southern blotting [25].
• In addition, GPDH digested with V8 protease and analyzed by one dimensional peptide mapping presented the same pattern for the three cell types examined [26].

References