Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
 6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of Mg(2+)-dependent and Na(+)-K(+)-stimulated ATPase in homogenates of rat retina were measured in the presence of increasing concentrations of oxidized glutathione (GSSG). The Mg(2+)-ATPase was not inhibited by GSSG at any of the concentrations tested. The Na(+)-K(+)-stimulated ATPase was not inhibited by 1 mM GSSG, but its activity was decreased by 20 and 35%, respectively, in the presence of 5 and 10 mM GSSG. Other enzymatic measurements using supernatant fractions of rat retina showed that 1-10 mM GSSG did not inhibit the activities of hexokinase, glucose-6-phosphate dehydrogenase, or glyceraldehyde-3-phosphate dehydrogenase. These results suggest that GSSG is not likely to exert significant deleterious changes on cellular processes, at least in cells and tissues in which normal glutathione (GSH) concentration is 2 mM or lower.
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PMID:Effects of oxidized glutathione on ATPase activities in rat retina. 165 10

Treatment of cultured neonatal cardiomyocytes with ethacrynic acid (EA) induced a rapid depletion of glutathione (GSH) that preceded a gradual elevation of cytosolic Ca2+ (monitored by phosphorylase a activation), a loss of protein thiols, and a marked inactivation of the thiol-dependent enzyme glyceraldehyde-3-phosphate dehydrogenase (G3PD). A subsequent decline of mitochondrial transmembrane potential (delta psi) and ATP occurred prior to the onset of lipid peroxidation which closely paralleled a loss of cardiomyocyte viability. The antioxidant N,N'-diphenyl-p-phenylenediamine prevented lipid peroxidation and cell death but had no effect on elevated cytosolic Ca2+, delta psi loss, GSH depletion, or G3PD inactivation. Pretreatment with the iron chelator, deferoxamine, decreased both lipid peroxidation and cell death. EA-induced lipid peroxidation and cell damage were also diminished by preincubation with acetoxymethyl esters of the Ca2+ chelators Quin-2 and ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid, even though cytosolic Ca2+ remained elevated. The extent of GSH depletion was unaltered by either chelator; however, Quin-2 did protect G3PD from inactivation by EA. An inhibitor of the mitochondrial respiratory chain, antimycin A, decreased EA-induced lipid peroxidation and cell death but had no effect on thiol depletion or elevated cytosolic Ca2+. These data suggest that cardiomyocyte thiol status may be linked to intracellular Ca2+ homeostasis and that peroxidative damage originating in the mitochondria is a major event in the onset of cell death in this cardiomyocyte model of thiol depletion.
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PMID:Thiol depletion induces lethal cell injury in cultured cardiomyocytes. 173 29

Selective modulation of brain glutathione (GSH) may assist the elucidation of the role of GSH in the central nervous system. Subcutaneous administration of diethyl maleate (DEM) depleted both cerebral and hepatic GSH in a dose- and time-dependent manner. While hepatic GSH levels returned to control levels 6 hr after DEM administration, brain GSH levels remained significantly lowered for up to 12 hr after administration of DEM. However, intrathecal administration of DEM resulted in a selective lowering of brain GSH without altering hepatic levels. Intrathecal administration of L-buthionine sulfoximine (L-BSO; 1.0 mmol/kg body wt) also depleted the GSH content of the brain and the levels remained low 24 hr after L-BSO administration. The extent of GSH depletion varied in different regions of the brain; maximal depletion was observed in the brainstem, followed by the cerebellum, striatum, cortex and hippocampus. Intrathecal administration of L-2-oxothiazolidine 4-carboxylate (OTC) resulted in a marginal elevation of GSH levels in the brain. There was considerable regional variation. A maximal elevation of 134% was seen in the hippocampus, 6 hr following the intrathecal administration of 8.0 mmol of OTC/kg body wt. The effect of the modulation of brain GSH levels on acrylamide (ACR)-induced neurotoxicity was examined. Depletion of GSH by pretreatment of mice with L-BSO or DEM (administered intrathecally) enhanced the toxicity of ACR as measured by the inhibition of brain glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity. The inhibition of GAPDH by ACR was attenuated by pretreatment of animals with OTC. Thus, brain GSH may play an important role in the detoxification of xenobiotics, in situ within the central nervous system.
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PMID:Selective modulation of glutathione in mouse brain regions and its effect on acrylamide-induced neurotoxicity. 173 14

Post-mortem biochemical analyses of dog lenses and of aqueous humour of a 2 year oral toxicity study in the dog with Fluvastatin (control, 1, 8 and 16 mg/kg/day) did not show any relationship to the observed lens opacities (3 animals out of 8 at 16 mg/kg/day). With respect to lens transparency, a daily dosage of 8 mg/kg/day Fluvastatin to dogs over a period of 2 years is non-cataractogenic. Mean data on lenticular enzyme activities (GPX, G6PH, GAPDH, ALD, AR, LDH, PFK and SDH) as well as measurements of GSH/GSSG, ATP, ADP, AMP, Gluc, Fruc, Sorb, G6P and F6P do not indicate changes which may directly lead to lens opacifications. Conformational changes of lens proteins (heat lability of PFK-activity), a shift in the albumin/IgG ratio of aqueous humour and equatorial lens protein composition changes (after isoelectrofocusing) were observed. The biological significance of these changes is unknown as the non-cataractogenic dose for lens opacities in beagle dogs is 8 mg/kg/day.
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PMID:Post-mortem biochemistry of beagle dog lenses after treatment with Fluvastatin (Sandoz) for 2 years at different dose levels. 215 8

The activity of the thiol-dependent enzyme glyceraldehyde-3-phosphate dehydrogenase (GPD), in vertebrate cells, was modulated by a change in the intracellular thiol:disulfide redox status. Human lung carcinoma cells (A549) were incubated with 1-120 mM H2O2, 1-120 mM t-butyl hydroperoxide, 1-6 mM ethacrynic acid, or 0.1-10 mM N-ethylmaleimide for 5 min. Loss of reduced protein thiols, as measured by binding of the thiol reagent iodoacetic acid to GPD, and loss of GPD enzymatic activity occurred in a dose-dependent manner. Incubation of the cells, following oxidative treatment, in saline for 30 min or with 20 mM dithiothreitol (DTT) partially reversed both changes in GPD. The enzymatic recovery of GPD activity was observed either without addition of thiols to the medium or by incubation of a sonicated cell mixture with 2 mM cysteine, cystine, cysteamine, or glutathione (GSH); GSSG had no effect. Treatment of cells with buthionine sulfoximine (BSO) to decrease cellular GSH by varying amounts caused a dose-related increase in sensitivity of GPD activity to inactivation by H2O2 and decreased cellular ability for subsequent recovery. GPD responded in a similar fashion with oxidative treatment of another lung carcinoma cell line (A427) as well as normal lung tissue from human and rat. These findings indicate that the cellular thiol redox status can be important in determining GPD enzymatic activity.
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PMID:Cellular recovery of glyceraldehyde-3-phosphate dehydrogenase activity and thiol status after exposure to hydroperoxides. 229 24

Utilizing glutathione ethyl ester (GSH-EE), the glutathione (GSH) level of lens epithelial cells can be increased as much as 1.9-fold. The epithelial cells maintain the additional GSH in the reduced form. This system was utilized to examine the relative effectiveness of cells with elevated GSH to withstand H2O2 insult. Three parameters were investigated, 86Rb accumulation, a measure of membrane function, ATP levels, an indication of overall metabolism and glyceraldehyde-3-phosphate dehydrogenase (GPD) activity, indicating intracellular enzyme susceptibility to oxidative insult. Under oxidative stress, much of the GSH is in the oxidized form but upon removal of the stress, rapidly returns to the reduced state. However, a loss of approximately 20% in GSH equilibrium levels has been consistently observed. Elevated GSH does not significantly increase the cells' ability to withstand or recover from oxidative stress. Indeed, elevated GSH was found to be somewhat deleterious, causing a decreased ability to recover from oxidative insult. However, in the case of GPD, a significant protection of activity was observed. The overall conclusion is that elevating intracellular GSH concentration does not increase the cells' overall ability to withstand oxidative damage.
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PMID:Does elevated glutathione protect the cell from H2O2 insult? 366 67

Nitric oxide (NO) is a readily diffusible, short-lived free radical with a multitude of organ-specific regulatory functions. Within the hepatocyte, NO production is associated with inhibition of mitochondrial electron transport enzyme activity, activation of soluble guanylyl cyclase, and inhibition of glyceraldehyde-3-phosphate dehydrogenase. However, while NO can regulate a number of hepatocyte functions, it is unknown whether NO production is hepatoprotective or hepatotoxic. Using isolated rat hepatocytes in primary short-term culture, we investigated the role of cytokine-mediated NO production in toxin-induced hepatocyte injury. In a model of acetaminophen (AM) hepatotoxicity, inhibition of cytokine-mediated NO production potentiated AM injury. In the presence of an inhibitor of NO synthesis, NG-monomethyl-L-arginine (L-NMMA), hepatocyte release of aspartate aminotransferase was increased twofold in the presence of 4.0 and 8.0 mM AM (P < 0.01). In addition, in the presence of AM, cytokine-mediated NO production was increased by 75% over baseline (P < 0.01). Maximum NO synthesis occurred at an AM concentration of 2 mM. A potential mechanism for the hepatoprotective effect of NO centers on its role in glutathione (GSH) homeostasis. In the presence of increasing concentrations of AM, hepatocyte GSH stores decreased in parallel in both control and cytokine-stimulated hepatocytes (ANOVA, P < 0.01). When cytokine-stimulated hepatocytes were exposed to 50 microM L-NMMA, NO release was ablated, while glutathione levels decreased by threefold in comparison to controls (P < 0.01). In the presence of increasing concentrations of AM, cytokine-treated cells exposed to 50 microM L-NMMA exhibited significant decremental decreases in GSH levels (P < 0.05). These data suggest that inhibition of cytokine-mediated NO production potentiates AM hepatoxicity by modulation of hepatocyte glutathione stores.
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PMID:Nitric oxide decreases oxidant-mediated hepatocyte injury. 801 16

A human small cell lung cancer cell line, U-1906, developed altered functional properties upon continuous in vitro cultivation. Cells obtained at late (U-1906 L) and early (U-1906 E) passages of cultivation differ in drug resistance to the cytostatic therapeutic agents cisplatin and doxorubicin. The U-1906 L cells are 1.6-fold and 1.3-fold more resistant to cisplatin and doxorubicin respectively, than are the U-1906 E cells. In the more resistant U-1906 L cells, the total glutathione (GSH plus GSSG) level is 40% lower, whereas the activities of GSH-linked enzymes such as GSH peroxidase and GSH transferases are significantly higher. Quantitative analysis with isoenzyme-specific ELISAs demonstrated increased concentrations of all three of the measurable GSTs, M1-1, M3-3 and P1-1, in the more resistant cells. The intracellular protein expression patterns of the U-1906 E and the U-1906 L cells are very similar as revealed by two-dimensional denaturing electrophoresis, but show significant alterations in the concentrations of some components. Two 35 kDa proteins of different pI values, the concentrations of which are increased in the U-1906 L cells, were both identified as glyceraldehyde-3-phosphate dehydrogenase, either by N-terminal or by internal amino acid sequence analysis. The present study demonstrates that the increased resistance of the U-1906 L cells may involve multiple detoxification mechanisms and that the contribution of the GSH-linked detoxification can be ascribed to the elevation of cytosolic GST isoenzymes, GSH peroxidase and glutathione reductase, rather than to the intracellular GSH concentrations.
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PMID:Acquired resistance to cisplatin and doxorubicin in a small cell lung cancer cell line is correlated to elevated expression of glutathione-linked detoxification enzymes. 802 Jan 51

Incubation of glyceraldehyde-3-phosphate dehydrogenase (GAPD) with sodium nitroprusside (SNP) decreased its activity in concentration- and time-dependent fashion in the presence of a thiol compound, with DTT being more effective than GSH. Both forward and backward reactions were effected. Coinciding with this, HgCl2-sensitive labelling of the protein by [32P]NAD+ also increased, indicating the stimulation of ADP-ribosylation. Treatment with SNP of GAPD samples from rabbit muscle, sheep brain and yeast inactivated the dehydrogenase activity of the three, but only the mammalian proteins showed ADP-ribosylation activity. The SNP-modified protein of rabbit muscle GAPD, freed from the reagent by Sephadex filtration showed a concentration-dependent restoration of the dehydrogenase activity on preincubation with DTT and GSH. Such thiol-treated preparations also gave increased ADP-ribosylation activity with DTT, and to a lesser extent with GSH. The SNP-modified protein was unable to catalyze this activity with the native yeast enzyme and native and heat-inactivated muscle enzyme. It was possible to generate the ADP-ribosylation activity in muscle GAPD, by an NO-independent mechanism, on dialysis in Tris buffer under aerobic conditions, and on incubating with NADPH, but not NADH, in muscle and brain, but not yeast, enzymes. The results suggest that the inverse relationship of the dehydrogenase and ADP-ribosylation activities is coincidental but not correlated.
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PMID:Inverse relationship of the dehydrogenase and ADP-ribosylation activities in sodium-nitroprusside-treated glyceraldehyde-3-phosphate dehydrogenase is coincidental. 821 90

We have developed a polymerase chain reaction (PCR)-based method to measure glutathione peroxidase (GSH-Px) mRNA levels. Expression was measured by multiplex competitive PCR amplification of (a) cDNA from GSH-Px and the "housekeeping" gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and (b) two internal standards consisting of single-base mutants of GSH-Px and GAPDH cDNA that cause either a loss (GSH-Px) or a gain (GAPDH) of an EcoRI restriction endonuclease recognition site. RNA extracted from a human papillomavirus-immortalized human bronchial epithelial cell line (BEP2D) was reverse transcribed. Serial dilutions of cDNA were PCR amplified in the presence of GSH-Px and GAPDH primers and quantified amounts of mutated internal standards. The amplified DNA was restriction digested with EcoRI and electrophoresed on an agarose gel stained with ethidium bromide, separating native from mutated products. Densitometry was performed to quantitate the bands. Our studies demonstrate that this technique measures the relative expression of GSH-Px to GAPDH precisely and reproducibly for studies done with the same master mixture and dilution of internal standards. Ratios of relative gene expression varied less than 25% from the mean. This technique will be useful to measure changes in gene expression, particularly when the amount of study sample is limited or the level of gene expression is low.
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PMID:Measurement of gene expression by multiplex competitive polymerase chain reaction. 823 2


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