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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although acute acrylonitrile (ACN) toxicity is very profound, the mechanism of its toxicity and immediate lethality is unclear. Many have suggested that ACN or its reactive metabolite acts directly at the target tissues, while others have implicated the release of CN ions from the parent compound as the toxic moiety. Since sodium thiosulfate (STS) is both an effective cyanide antidote and neutralizing agent capable of binding to reactive chemicals or metabolites, its antidotal role was investigated in mice exposed to 60 mg/kg intraperitoneal (IP) ACN injection. Treatment with an IP injection of 400 mg/kg of STS from 10 to 30 minutes before ACN administration protected animals from ACN-induced lethality. All mice appeared normal after prophylactic treatment with STS and showed no ill effects from ACN exposure. Similar data was observed when STS was administered 10 and 30 minutes after ACN administration. Non-protein sulfhydryl (NPSH) concentration was determined in the brain, kidneys, and liver of the mice exposed to a single or multiple doses of STS and ACN. The levels of NPSH were significantly lowered by ACN in the liver (45% of the control), and kidneys (51% of the control), whereas in the brain NPSH levels were least affected and decreased modestly (85% of the control) following either acute or chronic administration of acrylonitrile. The data indicate a marked protective effect of STS either before or after ACN exposure and this STS-induced antidotal response does not involve GSH in the brain.
Res Commun Mol Pathol Pharmacol 1995 Feb
PMID:Antidotal effect of sodium thiosulfate in mice exposed to acrylonitrile. 774 53

Liver homogenate glutathione (GSH) content, lipid peroxide levels and the activities of GSH metabolizing enzymes were studied in rats after 24 hours of galactosamine (GalN) treatment. Lipid peroxide levels increased whereas hepatic GSH content was decreased significantly. On the other hand, hepatic gamma-glutamyl cysteine synthetase activity was unaffected by GalN administration but gamma-glutamyl transpeptidase activity increased.
Res Commun Mol Pathol Pharmacol 1995 Feb
PMID:Hepatic gamma-glutamyl cysteine synthetase and gamma-glutamyl transpeptidase activities in galactosamine-treated rats. 774 60

Cyclophosphamide causes lung injury in rats through its ability to generate free radicals with subsequent endothelial and epithelial cell damage. In order to observe the protective effects of a potent anti-inflammatory antioxidant, curcumin (diferuloyl methane) on cyclophosphamide-induced early lung injury, healthy, pathogen free male Wistar rats were exposed to 20 mg/100 g body weight of cyclophosphamide, intraperitoneally as a single injection. Prior to cyclophosphamide intoxication oral administration of curcumin was performed daily for 7 days. At various time intervals (2, 3, 5 and 7 days post insult) serum and lung samples were analyzed for angiotensin converting enzyme, lipid peroxidation, reduced glutathione and ascorbic acid. Bronchoalveolar lavage fluid was analyzed for biochemical constituents. The lavage cells were examined for lipid peroxidation and glutathione content. Excised lungs were analyzed for antioxidant enzyme levels. Biochemical analyses revealed time course increases in lavage fluid total protein, albumin, angiotensin converting enzyme (ACE), lactate dehydrogenase, N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, acid phosphatase, lipid peroxide levels and decreased levels of glutathione (GSH) and ascorbic acid 2, 3, 5 and 7 days after cyclophosphamide intoxication. Increased levels of lipid peroxidation and decreased levels of glutathione and ascorbic acid were seen in serum, lung tissue and lavage cells of cyclophosphamide groups. Serum angiotensin converting enzyme activity increased which coincided with the decrease in lung tissue levels. Activities of antioxidant enzymes were reduced with time in the lungs of cyclophosphamide groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1995 Jan 12
PMID:Modulation of cyclophosphamide-induced early lung injury by curcumin, an anti-inflammatory antioxidant. 775 45

Cells in most culture media use cystine as the primary source of the cysteine precursor needed for glutathione (GSH) synthesis. As a result, GSH levels in many cultured cells may be limited by the rate of uptake of cystine into cells. We have shown that incubation with extracellular GSH can result in the reaction of GSH with cystine to generate cysteine, and that bovine pulmonary artery endothelial cells and lung type II epithelial cells transported cysteine more efficiently than cysteine. Cysteine transport was not affected by the presence of GSH. In cells incubated with GSH in RPMI-1640 there was a cystine-dependent increase in intracellular GSH levels. The increases in GSH were not prevented by the presence of acivicin, an inhibitor of the gamma-glutamyl transpeptidase reaction. Incubation with oxidized glutathione (GSSG) did not result in significant increases in intracellular GSH levels. We conclude that a primary mechanism by which extracellular GSH may increase intracellular GSH levels in cultured cells is by reducing cystine to cysteine, which is then rapidly transported and used as a substrate for intracellular GSH synthesis.
Am J Respir Cell Mol Biol 1995 Jun
PMID:Mechanisms of use of extracellular glutathione by lung epithelial cells and pulmonary artery endothelial cells. 776 29

The objectives of this study were to determine 1) whether reactive oxygen species generated upon postischemic reperfusion lead to oxidative stress in rat hearts, and 2) whether an exogenous prooxidant present in the early phase of reperfusion causes additional injury. Isolated buffer-perfused rat hearts were subjected to 30 min of hypothermic no-flow ischemia followed by 30 min of reperfusion. Increased myocardial content of glutathione disulfide (GSSG) and increased active transport of GSSG were used as indices of oxidative stress. To impose a prooxidant load, cumene hydroperoxide (20 microM) was administered during the first 10 min of reperfusion to a separate group of postischemic hearts. Reperfusion after 30 min of hypothermic ischemia resulted in a recovery of myocardial ATP from 28% at end-ischemia to 50-60%, a release of 5% of total myocardial LDH, and an almost complete recovery of both coronary flow rate and left ventricular developed pressure. After 5 and 30 min of reperfusion, neither myocardial content of GSSG nor active transport of GSSG were increased. These indices were increased, however, if cumene hydroperoxide was administered during early reperfusion. After stopping the administration of cumene hydroperoxide, myocardial GSSG content returned to control values and GSH content increased, indicating an unimpaired glutathione reductase reaction. Despite the induction of oxidative stress, reperfusion with cumene hydroperoxide did not cause additional metabolic, structural, or functional injury when compared to reperfusion without cumene hydroperoxide. We conclude that reactive oxygen species generated upon postischemic reperfusion did not lead to oxidative stress in isolated rat hearts. Moreover, even a superimposed prooxidant load during early reperfusion did not cause additional injury.
Mol Cell Biochem 1995 Mar 09
PMID:Glutathione disulfide as an index of oxidative stress during postischemic reperfusion in isolated rat hearts. 779 51

Oxidative desulfuration of diethyldithiocarbamate methyl ester (DDTC-Me), a thione xenobiotic and a metabolite of disulfiram, was studied. Using a rat liver microsomal incubation system, DDTC-Me was oxidized at the thionosulfur group, forming DDTC-Me sulfine. Only minimal desulfuration of DDTC-Me to S-methyl-N,N-diethylthiolcarbamate (DETC-Me) occurred. Desulfuration of DDTC-Me increased 4-fold when the microsomal incubation was supplemented with reduced glutathione (GSH) and increased 8-fold when both GSH and glutathione-S-transferase (EC 2.5.1.18) were added. Similar results were obtained using a simplified system containing DDTC-Me sulfine, GSH, and glutathione-S-transferase. This suggested that DDTC-Me sulfine is a stable intermediate formed before DDTC-Me is desulfurated to DETC-Me. This unprecedented desulfuration process can be explained as follows. GSH attacks the oxithiirane isomer of DDTC-Me sulfine, resulting in ring opening followed by loss of glutathione hydrodisulfide, which is reduced by GSH to oxidized glutathione and H2S. GSH can also reduce DDTC-Me sulfine to DDTC-Me. This mechanism is supported by in vitro studies. An approximately 1:1 stoichiometry was observed for the formation of H2S and DETC-Me. A 1:1 stoichiometry was also observed for the consumption of DDTC-Me sulfine, formation of DETC-Me plus DDTC-Me, and formation of oxidized glutathione. Glutathione hydrodisulfide was trapped by derivatization in situ using 4-vinylpyridine. Oxidative desulfuration of a series of dithiocarbamate esters also followed a similar mechanism.
Mol Pharmacol 1994 Dec
PMID:Glutathione- and glutathione-S-transferase-dependent oxidative desulfuration of the thione xenobiotic diethyldithiocarbamate methyl ester. 780 45

Previous studies have suggested that both cAMP-dependent signal transduction pathway and Ca2+/protein kinase C-dependent pathway are involved in GSH efflux from hepatocytes. In the present study, GSH efflux from Hep G2 cells, a human-derived hepatoma cell line, was further characterized. Both epidermal growth factor (0.1-10 ng/ml) and insulin (1 microgram/ml) significantly increased GSH efflux from Hep G2 cells. A fall in the membrane potential produced by the replacement of Na+ with equivalent K+ did not affect GSH efflux significantly. Neither ouabain, a Na+/K+ ATPase inhibitor, vanadate, a Ca2+ ATPase inhibitor, nor BaCl2, a K+ channel blocker, significantly affected the GSH efflux. Methionine (1mM) decreased GSH efflux from the cells, although total GSH content in the cells was not affected during the incubation time of 60 min. Signal transductions through tyrosine kinase-coupled receptors may also be involved in GSH efflux from hepatocytes.
Res Commun Mol Pathol Pharmacol 1994 Sep
PMID:Characterization of glutathione efflux from Hep G2 cells. 782 1

Glucose 6-phosphate dehydrogenase (G6PD) [EC 1.1.1.49] is inactivated by the incubation with cystamine very efficiently, but not by oxidized glutathione. This inactivation advanced following the incubation-time and concentration of cystamine. The inactivated-G6PD is restored its activity by the treatment of thioltransferase with 1 mM cysteamine or reduced glutathione (GSH) much more effectively than only by thiols. For the first time, we suggested thioltransferase can utilize cysteamine in stead of GSH during its thiol/disulfide exchange reaction activity.
Biochem Mol Biol Int 1994 Oct
PMID:Thioltransferase can utilize cysteamine as same as glutathione as a reductant during the restoration of cystamine-treated glucose 6-phosphate dehydrogenase activity. 786 98

The recovery of glutathione and its metabolising enzymes (glutathione disulfide reductase, glutathione peroxidase, thiol transferase, gamma-glutamyl transpeptidase and glutathione transferase) along with sulfhydryl groups and byproduct of lipid peroxidation (malondialdehyde) in the brain, spinal cord, kidney and liver of mice, altered during methylmercury chloride (MMC) intoxication, is recorded in post-therapeutic treatment with vitamins and monothiols. For this purpose ten groups of animals were intoxicated with 1 mg/kg MMC/day for 7 days. Out of these, one group was sacrificed on 8th day and one group was kept without toxicant for another seven days before sacrificing on 15th day. Study shows significant decrease of various biomolecules of glutathione metabolism during MMC application, which are further decreased with increasing the duration on 15th day. The trend is same in all the tissues with few exceptions. However, malondialdehyde, a byproduct of lipid peroxidation, is increased with increasing the duration after intoxication. Study also shows a significant recovery (in many cases a complete control level) of most of the components with one or the other chelator or with their combined therapy. Therefore, it is concluded from overall study that vitamins B complex and E, GSH (or its precursor NAHT) either alone or in combinations, are quite suitable for methylmercury post-therapy.
Cell Mol Biol (Noisy-le-grand) 1994 Mar
PMID:Ameliorative capacities of vitamins and monothiols post therapy in the restoration of methylmercury altered glutathione metabolism. 791 95

Rat liver and kidney gamma-glutamylcysteine synthetase (gamma GCS) had similar catalytic properties and consisted of heavy and light subunits, but the molecular structure of the two enzymes was not the same as evidenced by the results of SDS-PAGE and disc gel electrophoresis. Unlike kidney enzyme, most of liver gamma GCS was in a reduced enzyme form which did not have disulfide linkage between heavy and light subunits. Although the oxidized form of the two enzymes which subunits were linked with disulfide bond(s) could be dissociated to a similar extent by GSH, liver gamma GCS was inhibited by GSH to a much greater extent. These results suggest that the relative sensitivity of the gamma GCS enzymes to inhibition by GSH might be related to the inherent dissociability of heavy and light subunit of gamma GCS.
Biochem Mol Biol Int 1994 Mar
PMID:Biochemical regulation of the activity of gamma-glutamylcysteine synthetase from rat liver and kidney by glutathione. 791 45


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