Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1260386 (GSH)
 38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the nephrotoxic mechanisms of cephaloridine (CER), changes in renal contents of glutathione (GSH), glutathione disulfide (GSSG), reduced and oxidized nicotinamide adenine dinucleotide phosphates (NADPH and NADP) and changes in renal activities of glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase were examined for 15 days in rats that received single intravenous injections of CER in doses of 0 (control), 100 and 1,000 mg/kg body weight. Significantly different changes from the control group were observed in the 1,000 mg/kg group. The 1,000 mg/kg group showed elevations in renal NADP and NADPH contents and decrements in renal GSH content in the period of the 1st to 3rd hour after the CER-administration. Thus, the fall in renal GSH content was considered to be a cause for renal injury due to the oxygen radicals observed in the early period. After the 6th hour, the 1,000 mg/kg group showed decreases of renal glutathione peroxidase and glutathione reductase activities and increases of renal glucose-6-phosphate dehydrogenase activity as well as GSH content. Although accumulation of GSH in the kidney was clearly observed in the late period, the more highly aggravated renal injury was speculated to be due to the decreased level in the utilization of GSH according to the fall of renal glutathione peroxidase activity.
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PMID:Changes in glutathione peroxidase system and pyridine nucleotide phosphate levels in kidneys of cephaloridine-administered rats. 259 76

During postnatal development, gamma-glutamyl transpeptidase (gamma-GT), reduced glutathione (GSH), and L-glutamic acid (L-Glu) were assayed in the epididymides of rats at 5-day intervals between 10 and 60 days of age and compared to adult levels. gamma-GT activity (with gamma-glutamyl-p-nitroanilide as substrate) and L-Glu (nicotinamide adenine dinucleotide conversion-dependent assay) were measured photometrically, while GSH (o-phthalaldehyde reaction) was quantified with a fluorometric assay. In immature rats, the epididymal gamma-GT was very low but increased after 25 days of age in the caput and after 50 days of age in the cauda. The enzyme level in the epididymal caput was by far the highest in the adult rat reproductive tissues. The postnatal increase of gamma-GT in epididymal caput and cauda was associated with a decline of its substrate GSH and an accumulation of the product L-Glu. These observations provide evidence for the in vivo hydrolytic activity of gamma-GT and explain the high levels of L-Glu found in the epididymis of rats and other mammals.
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PMID:Gamma-glutamyl transpeptidase, glutathione, and L-glutamic acid in the rat epididymis during postnatal development. 290 Jun 57

The roles of subcellular components and, in particular, cytosol fractions and beta-nicotinamide adenine dinucleotide phosphate, reduced form (NADPH), in the regulation of rat hepatic and renal 5'-deiodination during fasting were assessed. 5'-deiodinase (5'-DI) activities in reaction mixtures were measured by using outer ring 125I-radiolabelled reverse triiodothyronine (rT3) as a substrate in the presence of 200 mumol/L NADPH. Subcellular components from rats fed ad libitum or fasted for 24, 48 or 72 hours were prepared by standard differential centrifugation. Cytosol was chromatographed on a Sephadex G-50 column to obtain Fraction A of molecular weight (Mr) greater than 60,000 and Fraction B of Mr approximately 13,000 and to exclude reduced glutathione (GSH) (Mr less than 400). 5'-DI activity in liver homogenates was reduced by 42% at 24 hours and by 59% at 48 hours of fasting. In reconstitution experiments, liver microsomes showed a progressive loss of 5'-DI activity, reaching a maximal reduction of 46% at 72 hours of fasting. Activation of microsomal deiodinase by whole liver cytosol was also significantly reduced at 24 hours of fasting and achieved a maximal reduction of 5'-DI activation of 42% at 48 hours before substantial but incomplete recovery at 72 hours. Cytosolic Fraction A and B were assessed in combination with fed microsomes and NADPH. A close correlation was demonstrated between the loss of hepatic 5'-DI supportive activity in whole cytosol and that of Fraction B but not A during fasting.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rat hepatic and renal 5'-deiodination of rT3 during fasting: supportive role of intermediate Mr cytosolic non-glutathione thiol cofactor and NADPH. 291 43

We investigated the mechanism of antitumor activity of the water-soluble derivative of menadione, menadione sodium bisulfite (vitamin K3), versus murine leukemia L1210. Vitamin K3, in concentrations greater than 27 microM, caused time- and concentration-dependent depletion of the acid-soluble thiol (GSH) pool. Maximal GSH depletion to 15% of control occurred at 45 microM vitamin K3. Vitamin K3-mediated GSH depletion and vitamin K3-mediated growth inhibition were abrogated by coincubation with 1 mM cysteine or 1 mM reduced glutathione but not by 1 mM ascorbic acid or 180 microM alpha-tocopherol. Low concentrations of vitamin K3 (9-27 microM) elevated both the GSH pool and the total glutathione pool, the latter to a greater degree. Vitamin K3 also caused an increased rate of superoxide anion generation by L1210, maximal at 45 microM vitamin K3 (300% of control), and a concentration-dependent depletion of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) and total nicotinamide adenine dinucleotide phosphate (NADP) pools. Forty-fifty % depletion of the NADPH pool occurred after exposure to 27 microM vitamin K3 and 100% occurred at 36 microM vitamin K3; 27 microM vitamin K3 is a nontoxic concentration of vitamin K3. Loss of NADPH and total NADP was prevented by coincubation with 1 mM cysteine but not by coincubation with ascorbic acid or alpha-tocopherol. We conclude that tumor cell growth inhibition by vitamin K3 is modulated by acid-soluble thiols and may be caused by GSH pool and/or NADPH depletion. Toleration of partial NADPH depletion by L1210 cells may indicate that a threshold level of NADPH loss of greater than 50% is necessary for toxicity. NADPH depletion may be a toxic effect common to quinone drugs. Equitoxic concentrations of vitamin K3, phylloquinone, lapachol, dichlorolapachol, and doxorubicin caused L1210 NADPH pools to deplete to 30 +/- 10 (SD), 60 +/- 10, 60 +/- 11, and 80 +/- 12% of control, respectively. In contrast, GSH depletion may not be a common mechanism of toxicity. Of these quinones, only vitamin K3 caused significant GSH depletion when studied in equitoxic concentrations.
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PMID:Modulation of cytotoxicity of menadione sodium bisulfite versus leukemia L1210 by the acid-soluble thiol pool. 299 58

Red cells collected in CPD and suspended in SAGM medium were stored in plastic (PVC) containers for 42 days at +4 degrees C. Comparison was made between aerobic storage (normal air exposure) and anaerobic storage (exposure to nitrogen gas). The air-exposed units showed a strong increase in pO2 and oxygen saturation as a result of oxygen penetration into the bags from outside. This resulted in a decrease in ATP and adenylate energy charge, a slower metabolization of adenine and hypoxanthine to AMP and IMP, respectively, and a faster decrease in red cell fluidity. To explain the findings it is concluded that aerobic storage causes an increased need of high-energy phosphate groups, possibly used for replacement of the phospholipid membrane bilayer or in repair of phosphate bonds in the cytoskeleton. It is further proposed that a slight formation of hydrogen peroxide from free oxygen radicals moderately increases the oxidation of reduced (GSH) to oxidized (GSSG) glutathione and slightly enhances the need for reduced nicotinamide-adenine dinucleotides mainly provided by increased flux through the pentose phosphate shunt.
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PMID:Effects of oxygen on red cells during liquid storage at +4 degrees C. 309 Jul 83

Streptozotocin (STZ) increased the activity of mouse hepatic glutathione (GSH) S-transferases assayed with 1-chloro-2,4-dinitrobenzene. Nicotinamide administered prior to STZ prevented the hyperglycemia indicative of STZ-induced diabetes, but had no effect on the increase in GSH S-transferase activity caused by the drug. Another diabetogenic agent, alloxan, did not alter GSH S-transferase activity. Thus, streptozotocin may be increasing GSH S-transferase activity directly, and not as a result of the diabetic state the drug induces. Two transferases were characterized from mouse liver cytosol. One was a homodimer with a subunit molecular weight of about 28,000 and a pI of about 8.2. The other was also a homodimer with a subunit molecular weight of about 27,500 and a pI of about 9.2. The pI 8.2 GSH S-transferase was induced by STZ, while the pI 9.2 transferase was decreased by the drug. At least one other transferase appeared to be induced by STZ. Two other nitroso compounds, chlorozotocin and diethylnitrosamine, also increased GSH S-transferase activity, suggesting that this effect may be nitroso related.
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PMID:Effect of streptozotocin on the glutathione S-transferases of mouse liver cytosol. 315 1

Studies were conducted in vivo with regenerating liver and in vitro with mammalian cells to determine the effects of selenium on cell proliferation and the stages of the cell cycle affected by selenium. Six ppm selenium as Na2SeO3 fed to weanling male F344 rats for 6 wk significantly reduced the percentage of 3H-labeled hepatocyte nuclei by one-half compared to 0.1 ppm selenium when [methyl-3H]thymidine was injected at 23 h post-two-thirds hepatectomy. Sampling was done at 30 h post-hepatectomy. A trend towards decreased 3H per DNA per labeled cell was also observed, suggesting that selenium decreased the rate of DNA synthesis as well as delaying the entry of cells into S phase (i.e., increasing the duration of G0-G1). Studies in vitro with H-4 "minimal deviation" hepatomas and 3T3 mouse fibroblasts demonstrated that selenium decreased the growth of these cells in a dose-dependent manner, and this inhibition was reversible upon removal of selenium from the growth medium. Cytokinetic analysis using fluorescence flow cytometry and microscopic techniques indicated that selenium treatment increased the duration of G1, S, and G2 phases of the cell cycle, while having no effect on mitosis under the conditions of our experiments. Biochemical analyses of H-4 cells demonstrated that selenium treatment caused a significant dose-dependent increase in oxidized and reduced glutathione (GSSG and GSH) as well as in the GSSG:GSH ratio as was previously observed in liver in vivo. In addition, glutathione reductase activity as well as the oxidized nicotinamide adenine dinucleotide phosphate:reduced nicotinamide adenine dinucleotide phosphate ratio was significantly increased with selenium treatment. These results indicate that selenium affects all "synthetic" stages of the cell cycle, and elevated GSSG or the GSSG:GSH ratio may explain the antiproliferative effects of selenium on cells.
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PMID:Effects of selenium on cell proliferation in rat liver and mammalian cells as indicated by cytokinetic and biochemical analysis. 405 23

Cell-free extracts of adult rat brain incubated with mevalonic acid-2-(14)C synthesize (14)C-labeled nonsaponifiable fractions consisting largely of squalene-(14)C. If the cofactor concentrations of the incubation medium are adjusted, much of the squalene can be induced to undergo turnover, with a resultant increase in (14)C-labeled digitonin-precipitable sterols, which include a small amount of cholesterol. The synthesis of labeled sterols is markedly increased in the presence of Mg(++) and depressed by nicotinamide. ATP, NADH, GSH, and glucose-6-phosphate are required for optimal synthesis of digitonin-precipitable material but, unlike Mg(++), are not essential. The cofactor-adjusted extracts also synthesize a complex ester mixture containing, in addition to cholesterol-(14)C, several compounds less polar than cholesterol. The biosynthesis of cholesterol in the extracts is a slow process; at least 12 hr of incubation is required for maximal sterol biosynthesis. A complex mixture of hydrocarbons accompanies squalene in the incubated extracts.
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PMID:Biosynthesis of squalene and cholesterol by cell-free extracts of adult rat brain. 430 11

The contribution of the metabolic state of human erythrocytes to maintenance of cellular deformability was studied during and after in vitro incubation in serum for periods up to 28 hr. An initial loss of membrane deformability became apparent between 4 and 6 hr when cellular adenosine triphosphate (ATP) levels were approximately 70% of initial values. Membrane deformability then remained stable between 6 and 10 hr. After 10 hr, when cellular ATP had decreased to < 15% of initial values, progressive parallel changes occurred in red cell calcium which increased 400% by 24 hr and in the viscosity of red cell suspensions which had risen 500-750% at 24 hr. A further progressive decrease in membrane deformability also occurred and was reflected by a 1000% increase in negative pressure required to deform the membrane. Red cell filterability decreased to zero as the disc-sphere shape transformation ensued. These changes were accompanied by an increase in ghost residual hemoglobin and nonhemoglobin protein. Regeneration of ATP in depleted cells by incubation with adenosine produced significant reversal of these changes, even in the presence of ouabain. Introduction of calcium into reconstituted ghosts prepared from fresh red cells mimicked the depleted state, and introduction of ATP, ethylenediamine tetraacetate (EDTA), and magnesium into depleted cells mimicked the adenosine effects in intact depleted cells. ATP added externally to 24-hr depleted cells was without effect. Simultaneous introduction of EDTA, ATP, or magnesium along with calcium into reconstituted ghosts prevented the marked decrease in deformability produced by calcium alone. Incorporation of adenosine diphosphate (ADP), nicotinamide adenine dinucleotide (NAD), NAD phosphate (NADP), NADP, reduced form (NADPH), glutatione, reduced form (GSH), inosine triphosphate (ITP), guanosine triphosphate (GTP), and uridine triphosphate (UTP) was without effect. These data suggest that a major role of ATP in maintenance of red cell viability relates to preservation of red cell membrane deformability. It is proposed that the changes seen in the physical properties of ATP-depleted erythrocytes represent ATP-calcium-dependent sol-gel changes occurring at the interface between the membrane and the cell interior, and that the sol-gel balance determines membrane deformability.
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PMID:Metabolic dependence of red cell deformability. 438 91

GSH added to rat liver homogenates inhibited respiration and increased GSSG formation approximately proportionally to the amount of GSH added; the effect was increased by added magnesium chloride. Added NADPH and citrate decreased GSSG formation and increased respiration; 6.0mm-nicotinamide prevented GSSG formation and increased respiration. There was a negative correlation between GSSG formation and oxygen uptake. It is suggested that the decrease in oxygen uptake is mainly due to GSSG concentration and also that in vivo a GSH-GSSG steady state occurs.
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PMID:A negative correlation between oxygen uptake and glutathione oxidation in rat liver homogenates. 439 Feb 8


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