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)

We have studied the levels of hepatic GSH in animals intoxicated with bromobenzene. A marked decrease of hepatic GSH was observed in poisoned rats. Such decrease was prevented by previous administration of lead nitrate, an inhibitor of DMES. In the rats treated with lead nitrate alone a rise in hepatic GSH was observed. Such protection was further observed by histological examination. The mechanism of protection exerted by lead nitrate against bromobenzene intoxication is discussed.
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PMID:Bromobenzene hepatotoxicity in lead pretreated rats. 96 72

The catalyzed reactions of GSH with organic nitrate and thiocyanate esters and with a series of chloronitrobenzene substrates have been investigated and the results used to formulate a mechanism for glutathione S-transferase catalysis. All the homogeneous preparations of the glutathione transferases that have been tested catalyze the reaction of GSH with organic nitrates and thiocyanates. The nature of the reaction with nitrate esters, resulting in the formation of GSSG rather than a thioether, has been investigated further. The presence of an additional nonsubstrate thiol decreased the formation of GSSG to an extent that cannot be explained by disulfide interchange. These results are interpreted to reflect the enzymatic formation of an unstable glutathione sulfenyl nitrite that undergoes subsequent non-enzymatic decomposition. Hammett plots of the catalytic constants of rat liver transferases B and C obtained with a series of 4-substituted 1-chloro-2-nitrobenzene substrates demonstrate a linear relationship with sigma- substituent constants, reflecting the nucleophilic nature of the enzymatic reactions and their strong dependence on the electrophilicity of the nonthiol substrate. These data suggest that the many diverse reactions catalyzed by the glutathione transferases may be formulated as a nucleophilic attack of enzyme-bound GSH on the electrophilic center of the second substrate. The final products observed reflect this primary event and the existence of subsequent nonenzymatic reactions.
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PMID:Mechanism for the several activities of the glutathione S-transferases. 97 64

The uptake of Cu+ by rat liver mitochondria is rapid and extensive. Respiration is stimulated by 10 microM Cu+ then inhibited and the inhibition could not be relieved with uncoupling agents. Collapse of the membrane potential is induced by 5-10 microM Cu+. These effects are partially inhibited by radical scavengers indicating the involvement of radical production in these events. Reduction of the GSH content and production of peroxidation products by higher amounts of Cu+ was also demonstrated. Swelling of non-respiring rat liver and heart mitochondria in sodium or lithium acetate was used to study effects of Cu+ on the Na+/H+ exchanger. Swelling is stimulated by 5-100 microM Cu+. In the presence of a radical scavenger the swelling is reduced. In sodium nitrate media diltiazem-sensitive stimulated swelling is observed. Amiloride was found to inhibit Cu(+)-induced efflux of Ca2+. At high concentrations of Cu+, a general increase in permeability was the dominant feature.
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PMID:Interaction of Cu+ with mitochondria. 166 75

The role of glutathione (GSH) and chromium (V) in chromium (VI)-induced nephrotoxicity in mice was investigated at 24 h after K2Cr(VI)2O7 ip injection. Nephrotoxicity was assessed by measurements of relative kidney weight and serum urea nitrogen. Cr(VI) nephrotoxicity was accompanied by decreased renal GSH and glutathione reductase (GSSG-R) levels. Pretreatment with buthionine sulfoximine, an inhibitor of GSH biosynthesis, enhanced Cr(VI)-induced nephrotoxicity, and remarkably diminished kidney GSH and GSSG-R levels. In contrast, pretreatment with glutathione methyl ester, a GSH-supplying agent, prevented Cr(VI) from exerting a harmful effect on mouse kidney and restored kidney GSH level. Administration of a Cr(V) compound, K3Cr(V)O8, induced much higher toxicity in mouse kidney than Cr(VI), but it failed to diminish renal GSH level. Another Cr(V) compound, Cr(V)-GSH complex, and Cr(III) nitrate did not cause a nephrotoxic effect in mice. The mechanism of Cr(VI)-induced nephrotoxicity was explained using GSH and Cr(V).
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PMID:In vivo nephrotoxicity induced in mice by chromium(VI). Involvement of glutathione and chromium(V). 172 73

Anaerobically grown Escherichia coli accumulate active manganese-containing superoxide dismutase (MnSOD) upon exposure to diamide. This induction requires de novo biosynthesis of MnSOD. Catalase, glutathione disulfide reductase, and glucose-6-phosphate dehydrogenase were also induced by diamide in anaerobic E. coli. A GSH-negative strain of E. coli did not produce MnSOD under anaerobic conditions and was as responsive to diamide as was the wild type strain. Diamide which had been prereduced, by incubation with GSH, was ineffective. NO3- plus paraquat, which elicits increased anaerobic biosynthesis of the MnSOD polypeptide, but not of active MnSOD, synergized with diamide in the induction of active MnSOD. A similar increase in the ability of diamide to cause anaerobic biosynthesis of active MnSOD was seen when the production of the MnSOD polypeptide was increased by isopropyl-beta-D-thiogalactopyranoside, in a strain bearing the MnSOD gene under the control of the tac promoter. These results are explained in terms of a dual action of diamide, i.e. at both the transcriptional and the maturational levels of biosynthesis of MnSOD. Oxidative inactivation of an Fe(II)-containing repressor and oxidative facilitation of insertion of manganese, in place of iron, into the nascent MnSOD polypeptide, are the postulated bases of this dual action.
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PMID:Anaerobic biosynthesis of the manganese-containing superoxide dismutase in Escherichia coli. Effects of diazenedicarboxylic acid bis(N,N'-dimethylamide) (diamide). 225 40

To monitor free radical scavenging properties of drugs, the 'stable' radical 2,2,6,6-tetramethylpiperidino-1-oxyl (TEMPO) was used. The sydnonimine molsidomine (SIN-1) effectively reduced the ESR signal whereas the nitrate isosorbidemononitrate (ISMN) did not. Thiol reagents like 2-mercaptopropionylglycine (MPG) or glutathione (GSH) only were effective in the presence of Fe2+ or Fe3+. Protein-bound iron in hemoglobin proved about four times more effective in reducing ESR signal height by thiols. It is suggested that the decrease in thiol content adds to the lack in protein bound iron of hemoglobin to induce the burst of free radicals in hypoxia (ischemia) and reperfusion.
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PMID:Free radical scavenging drugs, assessed by ESR studies: influence of hemoglobin. 285 30

The presence of glutathione (GSH) S-transferase activity, using 1-chloro-2, 4-dinitrobenzene (CDNB) as a substrate, has been established in the cytosolic fraction of the toxigenic (aflatoxin producing) and nontoxigenic strains of Aspergillus flavus. Significant differences in the GSH S-transferase activity were observed between the toxigenic and non-toxigenic strains. A positive correlation has been demonstrated for the first time between aflatoxin formation and a biochemical parameter, namely GSH S-transferase activity. The evidence in support of A. flavus GSH S-transferase induction by endogenous aflatoxins is as follows: (i) the age-related production of aflatoxin follows the same pattern as the cytosolic GSH S-transferase activity profile; (ii) significantly higher enzyme activity was associated with mycelia of a toxigenic strain grown in medium supporting high aflatoxin production (sucrose-low-salts medium) while the enzyme activity was low in medium producing less aflatoxin (glucose-ammonium nitrate medium). The GSH S-transferase activity of the non-toxigenic strain was hardly affected by a change in the medium as it produces no aflatoxins; and (iii) the toxigenic strain demonstrated significantly higher apparent Vmax. with no change in Km as compared with the non-toxigenic strain. This indicates that the enzyme induction by endogenous aflatoxins is similar to the action of phenobarbitol and other inducing drugs (Kaplowitz et al., 1975).
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PMID:Positive correlation exists between glutathione S-transferase activity and aflatoxin formation in Aspergillus flavus. 314 Aug 4

total glutathione (GSH) efflux was studied in isolated rat hepatocyte suspensions at repleted GSH content (45-55 nmol/10(6) cells). The increase in concentrations of medium K+ in place of Na+ caused a parallel fall in membrane potential and total GSH efflux. Ouabain (1 mM) and replacement of Na+ with choline caused a gradual fall in membrane potential and GSH efflux. Hyperpolarization of hepatocytes with lipophilic anions, thiocyanate, and nitrate was associated with significantly increased efflux. Total GSH efflux was inhibited by increasing concentrations of fructose, antimycin A, and carbonyl cyanide p-trifluoromethoxyphenylhydrazone, and there was a direct relationship between the rate of efflux and cellular ATP. Changes in total GSH efflux were paralleled by changes in GSH determined by high-performance liquid chromatography. Vanadate markedly inhibited efflux but caused only a modest decrease in cellular ATP. Fructose, antimycin A, and vanadate did not affect membrane potential or cell volume under the conditions at which efflux was inhibited. These results suggest independent requirements for both membrane potential and ATP in the transport of GSH.
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PMID:Effect of membrane potential and cellular ATP on glutathione efflux from isolated rat hepatocytes. 317 40

Glutathione (GSH) is released into hepatic sinusoids by a carrier-mediated process. The importance of transmembrane potential difference (PD) as a driving force for hepatic efflux of GSH from isolated perfused rat liver was investigated. The membrane PD was measured using intracellular microelectrodes as PD was altered over the physiological range by ion substitution in the perfusate. The effect of a change in membrane PD on the rate of efflux of GSH into the perfusate was determined. Because GSH carries a net negative charge at physiological values of pH, we predicted that hyperpolarization of cells would increase efflux, whereas depolarization would decrease efflux. Three different manipulations were used to depolarize the hepatocyte membrane to a similar degree, and variable effects on GSH efflux were observed. Substitution of Cl with gluconate in the perfusate depolarized the hepatocyte but had no effect on GSH efflux, whereas substitution of Na with choline in the perfusate increased GSH efflux to 110% of basal values. Perfusion with K+ inhibited GSH efflux by 21%. The latter two manipulations were associated with evidence of hepatic injury. Hyperpolarization of the hepatocyte also had variable effects on GSH efflux. Substitution of Cl with nitrate in the perfusate transiently increased the membrane PD and decreased GSH efflux, whereas perfusion with glucagon caused a sustained increase in membrane PD but did not alter GSH efflux rates. None of the latter manipulations was associated with hepatic injury and thus no consistent relationship between membrane PD and sinusoidal efflux of GSH was demonstrated. We conclude that in the isolated perfused rat liver, efflux of GSH is not driven directly by membrane PD.
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PMID:Hepatic efflux of glutathione by the perfused rat liver: role of membrane potential difference. 318 47

The sulfhydryl (SH) oxidant diamide activated in a concentration-dependent manner ouabain-resistant (OR), Cl-dependent K flux in both low potassium (LK) and high potassium (HK) sheep red cells as determined from the rate of zero-trans K efflux into media with Cl or Cl replaced by NO3 or methane sulfonate (CH3SO3). Diamide did not alter the OR Na efflux into choline Cl. The diamide effect on K efflux appeared after 80% of cellular glutathione (GSH) was oxidized to GSSG, its disulfide. The stimulation of K efflux was completely reversed during metabolic restitution of GSH, a process that depended on the length of exposure to and the concentration of diamide. The action of diamide on both the K:Cl transporter and GSH was also fully reversed by the reducing agent dithiothreitol (DTT). Diamide apparently oxidized the same SH groups alkylated by N-ethylmaleimide (NEM) (Lauf, P.K. 1983. J. Membrane Biol. 73:237-246). Like NEM, diamide activated K:Cl transport several-fold more in LK cells than in HK cells, and the effect on LK cells was partially inhibited by anti-L1, the allo-antibody known to inhibit OR K fluxes.
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PMID:Thiol-dependent K:Cl transport in sheep red cells: VIII. Activation through metabolically and chemically reversible oxidation by diamide. 336 66


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