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)

The ability of transparent and cataractous human, rabbit and mice lenses to metabolize hydrogen peroxide in the surrounding medium was evaluated. Using a chemiluminescence method in a system of luminol-horseradish peroxidase and a photometric technique, the temperature-dependent kinetics of H2O2 decomposition by lenses were measured. The ability of opaque human lenses to catalyze the decomposition of 10(-4) M H2O2 was significantly decreased. However, this was reversed by the addition of GSH to the incubation medium. Incubation of the mice lenses with the initial concentration H2O2 10(-4) M led to partial depletion of GSH in normal and cataractous lenses. Human cataractous lenses showed decreased activities of glutathione reductase, glutathione peroxidase (catalyzing reduction of organic hydroperoxides including hydroperoxides of lipids), superoxide dismutase, but no signs of depletion in activities of catalase or glutathione peroxidase (utilizing H2O2). The findings indicated an impairment in peroxide metabolism of the mature cataractous lenses compared to normal lenses to be resulted from a deficiency of GSH. An oxidative stress induced by accumulation of lipid peroxidation products in the lens membranes during cataract progression could be considered as a primary cause of GSH deficiency and disturbance of the redox balance in the lens.
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PMID:Peroxide-metabolizing systems of the crystalline lens. 173 65

Gastric mucous epithelial cells may represent a first line of defense against reactive oxygen species that are generated within the gastric lumen. However, little is known about their defenses against oxidant species. This study examined the importance of the glutathione (GSH) redox cycle and of endogenous catalase as antioxidant defenses in cultured gastric mucous cells. Cultured rat gastric mucous cells were exposed to H2O2 generated by glucose oxidase acting on glucose or to nascent H2O2 for 5 h. Cytotoxicity was quantified by measuring 51Cr release from prelabeled cells. The effects of inhibition of the GSH redox cycle and of endogenous catalase were examined. Glucose oxidase caused a dose-dependent increase of 51Cr release. Similarly, nascent H2O2 damaged the cells dose dependently. Pretreatment with 1,3-bis(chloroethyl)-1-nitrourea (inhibitor of GSH reductase) dose dependently increased glucose oxidase-induced 51Cr release. Preincubation with buthionine sulfoximine (inhibitor of gamma-glutamyl-cysteine synthetase), which lowered intracellular GSH content, enhanced glucose oxidase-induced damage in a dose-dependent manner. Pretreatment with diethyl maleate, which covalently binds GSH as catalyzed by GSH transferase, also enhanced the sensitivity to lysis by glucose oxidase. However, inhibition of endogenous catalase activity by 3-amino-1,2,4-triazole did not significantly alter glucose oxidase- or nascent H2O2-induced 51Cr release. These results suggest that the GSH redox cycle rather than endogenous catalase plays a critical role in intracellular antioxidant defense in cultured gastric mucous cells.
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PMID:Antioxidant defenses of cultured gastric cells against oxygen metabolites: role of GSH redox cycle and endogenous catalase. 176 53

Mercuric ion (Hg(II)) causes oxidative tissue damage in kidney cortical cells. We studied the in vitro effects of Hg(II) on hydrogen peroxide (H2O2) production by rat kidney mitochondria, a principal intracellular target of Hg(II). In mitochondria supplemented with a respiratory chain substrate (succinate or malate/glutamate) and an electron transport inhibitor (antimycin A (AA) or rotenone), Hg(II) (30 nmol/mg protein) increased H2O2 formation approximately 4-fold at the ubiquinone-cytochrome b region (AA-inhibited) and 2-fold at the NADH dehydrogenase region (rotenone-inhibited). Concomitantly, Hg(II) increased iron-dependent lipid peroxidation 3.5-fold at the NADH dehydrogenase region, but only by 25% at the ubiquinone-cytochrome b region. The mitochondrial concentration of reduced glutathione (GSH) decreased both with incubation time and Hg(II) concentration. Hg(II), at a concentration of 12 nmol/mg protein, caused almost complete depletion of measurable GSH in substrate-supplemented mitochondria after a 30-min incubation. In electron transport-inhibited mitochondria, Hg(II) caused greater depletion of GSH in rotenone-inhibited than in AA-inhibited mitochondria, consistent with the effects of Hg(II) on lipid peroxidation. These results suggest that Hg(II) at low concentrations depletes mitochondrial GSH and enhances H2O2 formation in kidney mitochondria under conditions of impaired respiratory chain electron transport. The increased H2O2 formation by Hg(II) may lead to oxidative tissue damage, such as lipid peroxidation, observed in mercury-induced nephrotoxicity.
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PMID:Mercury-induced H2O2 production and lipid peroxidation in vitro in rat kidney mitochondria. 176 76

Lenses from normal rabbits, mice, rats, cattle, guinea pigs, lambs, chicken, cats, baboons, blue acara (fish) and dogs were examined for the presence of H2O2. No previous reports exist on the presence and levels of H2O2 in normal eye lenses. Freshly isolated lenses of these animals were extracted with trichloroacetic acid and the extract neutralized with Tris. H2O2 was assayed in these extracts by reacting them with 1-14C-alpha-ketoglutarate and measuring the 14CO2 produced by peroxide-dependent decarboxylation. Peroxide of the order of 10(-4)M was detected in most of the lenses except in baboons wherein it exists between 10(-4) and 10(-5)M. Culture experiments with rat lenses demonstrated that GSH may make a major contribution to the formation of H2O2 in the intact lens in vivo.
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PMID:Hydrogen peroxide in the eye lens: radioisotopic determination. 179 Jul 13

The involvement of glutathione (GSH) dependent processes in the detoxification of 4-hydroxy-2-nonenal (4HNE) was investigated using Chinese hamster fibroblasts and clonogenic cell survival. GSH reacted, in a dose-dependent fashion, with 4HNE in phosphate buffer at pH 6.5, leading to the disappearance of 4HNE. The addition of glutathione transferase activity (GST) facilitated a more rapid disappearance of 4HNE but the reaction was still dependent on the concentration of GSH. When cell cultures were exposed to the reaction mixtures, 4HNE cytotoxicity was also reduced in a manner which was dependent on the concentration of GSH. When 2.16- or 1.08-mM GSH were incubated in phosphate buffer with 1.08-mM 4HNE in the presence or absence of GST, then mixed with media and placed on cells for 1 h, the cytotoxicity associated with exogenous exposure to free 4HNE was abolished. GSH depletion (greater than 90%) using buthionine sulfoximine (BSO) was accomplished in control (HA1) and H2O2-resistant variants derived from HA1. GSH depletion resulted in enhanced cytotoxicity of 4HNE in all cell lines. This BSO-induced sensitization to 4HNE cytotoxicity was accompanied by a significant reduction in the ability of cells to metabolize 4HNE. The magnitude of the sensitization to 4HNE toxicity caused by GSH depletion was similar to the magnitude of the reduction in the ability of cells to metabolize 4HNE. These results support the hypothesis that GSH and GST provide a biologically significant pathway for protection against aldehydic by-products of lipid peroxidation.
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PMID:Glutathione dependent metabolism and detoxification of 4-hydroxy-2-nonenal. 179 27

S-(1,2-Dichlorovinyl)-L-cysteine (DCVC) sulfoxide, a putative metabolite of the toxic cysteine S-conjugate DCVC, was synthesized by the reaction of DCVC with H2O2 and characterized by fast atom bombardment mass spectrometry (FAB-MS) and proton nuclear magnetic resonance spectroscopy. DCVC sulfoxide was stable when kept at room temperature overnight in phosphate buffer (pH 6.8-7.8) or when heated in phosphate buffer (pH 7.2 or 7.6) or H2O (pH 3.5 or 10.5) for 20 min at 37 degrees C. However, in the presence of glutathione (GSH), DCVC sulfoxide was readily converted to S-[1-chloro-2-(S-glutathionyl)vinyl]-L-cysteine sulfoxide (I), a product formed by the Michael addition of GSH to DCVC sulfoxide followed by the loss of HCl. Evidence for the mechanism of this reaction was obtained by the finding that DCVC, which cannot act as a Michael acceptor, did not react with GSH under conditions similar to those used with DCVC sulfoxide. When the reaction of DCVC sulfoxide with GSH was carried out at room temperature and pH 7.4, formation of I was complete at 5 min, but when the reaction was carried out for 2 h at pH 6.0 or 4.4 at 37 degrees C, product formation was nearly 37 or 3% of that formed at pH 7.4, respectively; product formation did not increase when the reaction was carried out at pH 8.5. When DCVC sulfoxide (100 mg/kg) was administered to rats, hepatic and renal reduced nonprotein thiol concentrations were decreased at 1 h to 74 and 27% of that in control rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reactivity of cysteine S-conjugate sulfoxides: formation of S-[1-chloro-2-(S-glutathionyl)vinyl]-L-cysteine sulfoxide by the reaction of S-(1,2-dichlorovinyl)-L-cysteine sulfoxide with glutathione. 180 49

We report that an internal and non-UV-dependent type of neoplasia, the human cervical intraepithelial neoplasia (SIL), is also deficient in catalase activity, like the UV-induced tumors in the autosomal recessive human epithelial disease, xeroderma pigmentosum (XP). Whether or not the lesions are papillomavirus (HPV) positive in the different categories of preneoplastic and neoplastic extracts, the following parameters are affected: i), catalase activity level; ii), kinetic profile of catalase activity; iii), H2O2 increase. Mathematical treatment of these parameters (CONSTEL-Program), unambiguously distinguishes between normal and pathological cases. Such analyses make it possible to grade the pathological samples into 4 classes, depending on their deviance from normality. These classes may be correlated with the gradual steps in the process of malignant transformation defined by histological and clinical diagnosis. We found conformity between catalase activity and histological analyses in 66 biopsies, out of a total of 100 biopsies (35 patients). Moreover, 23 patients presenting decreased catalase activities in 31 biopsies showed disease progression after 3 to 6 months contrary to surgery histological data. We show that ATP synthesis in the presence of catalase and H2O2 (further aspect of catalase function), may occur in neoplastic extracts at much lower concentrations of H2O2 than in normal extracts. Thus, the catalase abnormality seems to be a good tool to study pre-neoplastic to neoplastic evolution of lesions and their adjacent tissues of the lower female genital tract; furthermore, i) it provides an earlier, more powerful means of detecting micro-SIL in progression to squamous cell carcinoma, than combined clinical and histological examinations; ii) model for investigating drugs such as in situ H2O2 scavengers or agents increasing glutathione peroxidase activity (GSH).
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PMID:Catalase-associated abnormalities and H2O2 increase in pre-neoplastic and neoplastic lesions of the human lower female genital tract and their near adjacent epithelia. 182 Jan 75

N-acetylcysteine (NAC) is rapidly de-acetylated in vivo to cysteine (CYSH), a precursor of glutathione (GSH) which is an antioxidant in cells and body fluids. We investigated the effect of oral administration of N-acetyl cysteine for 5 days on the spontaneous and stimulated generation of hydrogen peroxide (H2O2) and superoxide anion (O2-) from human and rat phagocytic leucocytes. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) in control rats and rats given NAC in their drinking water. Neutrophils (PMNL) were harvested from whole blood in normal nonsmoking volunteers before and after NAC was given by mouth. The stimulated release of H2O2 and O2 from both rat AM and human PMN was not changed by administration of NAC. However, a small but significant increase was observed in both the spontaneous generation of O2- from rat AM and the spontaneous generation of H2O2 from human PMNL. Administration of NAC significantly increased cysteine levels in human plasma and rat BAL, but the levels in human PMNL and rat AM after NAC did not differ from control levels. GSH levels were not altered significantly by NAC.
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PMID:Lack of effect of N-acetylcysteine on the release of oxygen radicals from neutrophils and alveolar macrophages. 188

Glutathione transferases (GSTs) in Class Pi (rat GST-P (7-7) and human GST-pi) were inactivated by treatment with 0.05-1 mM hydrogen peroxide (H2O2), while GSTs in Class Alpha (1-2) and Class Mu (3-3, 3-4) were not, even with 5 mM H2O2. In the presence of 1 mM reduced glutathione (GSH), the inactivated GST-P (-pi) was effectively reactivated by the action of thioltransferase, which had been partially purified from rat liver by GSH-Sepharose affinity chromatography and gel filtration using Sephadex G-75. Thus, inactivation of GST-P by H2O2 was indicated to involve concomitant formation of disulfide bonds between cysteinyl residues. Single GST-P or GST-pi subunits are known to have four cysteinyl residues at the same positions, which can react with sulfhydryl group modifiers. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, GST-P treated with 1 mM H2O2 showed several extra bands, at least three, with apparent molecular weights of 21.5, 18, 37 kDa in addition to the native GST-P subunit band with a molecular weight of 23.5 kDa. These extra bands were identified as inactive forms since they returned to the native band with accompanying restoration of the activity when treated with dithiothreitol, mercaptoethanol, or thioltransferase. Disulfide bonds were formed mainly within subunits, causing an apparent reduction in molecular weight, only small amounts of binding between subunits being observed.
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PMID:Modulation of class Pi glutathione transferase activity by sulfhydryl group modification. 189 44

Rat liver microsomes contain a membrane-bound GSH S-transferase (GSH-tr), an enzyme that is involved in the detoxication of xenobiotics. Also located on rat liver microsomes is the cytochrome P450 system, an enzyme complex that catalyzes the conversion of several xenobiotics into reactive intermediates. In this study, it was demonstrated that reactive products from alpha-methyldopa formed by the cytochrome P450 system are able to stimulate microsomal GSH-tr. Also, products formed from alpha-methyldopa that are generated by H2O2-horseradish peroxidase and tyrosinase are able to stimulate the activity of microsomal GSH-tr. GSH was able to prevent the activation of microsomal GSH-tr. Our results indicate that the ortho-quinone or semi-ortho-quinone radical of alpha-methyldopa is responsible for the stimulation of microsomal GSH-tr, probably via arylation of the free sulfhydryl group of microsomal GSH-tr. This conclusion was supported by the observation that 4-methyl-ortho-quinone itself was able to stimulate microsomal GSH-tr via sulfhydryl arylation. Our results are in conformity with the hypothesis that reactive products formed by the cytochrome P450 complex are able to stimulate microsomal GSH-tr and possibly in this way enhance their detoxication.
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PMID:Activation of the microsomal glutathione S-transferase by metabolites of alpha-methyldopa. 189 94


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