Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: KEGG:D00031 (Glutathione)
5,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutathione: dehydroascorbic acid oxidoreductase (EC 1.8.5.1) has been purified to essential homogeneity by precipitation with (NH4)2SO4, and ion-exchange chromatography on CM-Sephadex and DEAE-cellulose. The molecular weight is 24200 Dalton as determined by SDS-PAG-electrophoresis. The amino acid composition was analysed. The esed. The enzyme ist specific for glutathione as H-donor and it reduces the L-threo-diasteromer faster than the L-erythro- and D-erythro-dehydroascorbic acid. The enzyme is inhibited by iode acetic acid and N-ethyl-maleinimide. Zero-order kinetics was only observed for the hydrogen-acceptor but not for glutathione.
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PMID:[Glutathatione-dehydrogenase of wheat flour. Purification and properties (author's transl)]. 100 16

The activities of Superoxide Dismutase (SOD), Glutathione Peroxidase (GSH-Px) and Catalase (CAT) in the ischemic cerebral tissue following the unilateral middle cerebral artery occlusion of rats were assessed. In comparison with the sham-operated rats, both SOD and GSH-Px activity in the ischemic area (striatum and fronto-parietal cortex) were significantly reduced by 30 min. of ischemia, GSH-Px activity in the peri-ischemic area (parieto-parasagittal) was significantly reduced as well. It was shown that in the striatum the GSH-Px activity was much higher than that in the cortex. According to our data, it was suggested that in the ischemic condition, cerebral Superoxide (O2-) and Hydrogen Peroxide (H2O2) were accumulated, and thus the polyunsaturated fatty acids in the neuronal membrane were trapped by these free radical. And such a process resulted in neuronal damage. It implicated that the oxygen free radical might be involved in the neuronal damage induced by Dopamine, since the O2- and H2O2 were excessively generated during the oxidative deamination of Dopamine and the free radical scavengers, SOD and GSH-Px were decreased concomitantly in the cerebral ischemic tissue.
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PMID:[A study on the activity of three antioxidant enzymes in the brain of experimental acute cerebral ischemia]. 130 99

Glutathione-activated neocarzinostatin chromophore (NCS-Chrom) generates bistranded lesions at AGC.GCT sequences in DNA, consisting of an abasic site at the C residue and a strand break at the T residue on the complementary strand, due to hydrogen atom abstraction from C-1' and C-5', respectively. Earlier work showed that 2H from C-5' of T was selectively abstracted by the radical center at C-6 of activated NCS-Chrom, supporting a proposed model of the active-drug/DNA complex. However, since under the conditions used breaks at the T exceeded their inclusion in bistranded lesions, it was not clear what fraction of the hydrogen transfer represented bistranded lesions. Since virtually all abasic sites at the C are part of a bistranded lesions, hydrogen transfer from C-1' of C into the drug should reflect only the bistranded reaction. Accordingly, a self-complementary oligodeoxynucleotide 5'-GCAGCICTGC-3' was synthesized in which the C contained 2H at the C-1' position. In order to eliminate an 2H isotope effect on the transfer and to increase the extent of the bistranded reaction, an I residue was substituted for the G opposite the C residue. Sequencing gel electrophoretic analysis revealed that under one-hit kinetics, 37% of the damage reaction was associated with abasic site (alkali-labile break) formation at the C residue and 48% with direct strand breaks at the T residue. Thus, 74% of the damage involved a bistranded lesion. 1H NMR spectroscopic analysis of the reacted chromophore showed that 2H had been selectively transferred into the C-2 position to the extent of approximately 22%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selective abstraction of 2H from C-1' of the C residue in AGC.ICT by the radical center at C-2 of activated neocarzinostatin chromophore: structure of the drug/DNA complex responsible for bistranded lesion formation. 139 Jun 98

Induction of the expression of the mammalian heme oxygenase gene appears to be a general response to oxidant stress. In view of the role of glutathione in protecting cells against solar UVA radiation and other forms of oxidant stress, we have investigated the relationship between intracellular glutathione levels and the inducibility of the human heme oxygenase gene after treatment of populations of cultured skin fibroblasts with either UVA radiation or hydrogen peroxide. We observe a clear relationship between cellular glutathione status and both the constitutive and oxidant-inducible accumulation of heme oxygenase mRNA. Glutathione depletion may lead to enhanced gene expression either as a result of the potentiated accumulation of active oxygen intermediates or as a result of the direct influence of glutathione on a critical target involved in signal transduction.
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PMID:Endogenous glutathione levels modulate both constitutive and UVA radiation/hydrogen peroxide inducible expression of the human heme oxygenase gene. 174 12

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

The efficacy of 3-tert-butyl-4-hydroxyanisole (BHA) as a chemopreventive agent against chemically induced cancer or toxicity may involve the direct modulation of cytochrome P-450 dependent monooxygenase function. This hypothesis was investigated by using purified rabbit cytochrome P-450IA2 and P-450IIB4 in a reconstitution system with purified NADPH:cytochrome P-450 oxidoreductase and L-alpha-dilauroylphosphatidylcholine. BHA caused a concentration-dependent decrease in cytochrome P-450IIB4 dependent 7-ethoxycoumarin O-deethylation, cyclohexane hydroxylation, and benzphetamine N-demethylation activities (IC50; 28, 75, and 290 microM, respectively) and in cytochrome P-450IA2 dependent 7-ethoxyresorufin O-deethylation and acetanilide para hydroxylation activities (IC50 approximately 225 microM). The inhibition of monooxygenation activity was accompanied by redox cycling due to the tert-butylquinone produced during BHA metabolism, as measured by increased NADPH and oxygen consumption or hydrogen peroxide and superoxide anion production. Glutathione was shown to reverse this redox cycling phenomenon but did not reverse the BHA-dependent inhibition of monooxygenation activity. Using standard steady-state kinetic analyses, BHA was shown to be a mixed-type competitive inhibitor of benzphetamine metabolism by cytochrome P-450IIB4, suggesting that BHA does not simply compete as an alternate substrate for the hemoprotein but must also bind to another catalytically functional form of cytochrome P-450. BHA was shown to bind as a ligand to both purified and microsomal cytochrome P-450IA2, resulting in a low to high (type I) spin-state perturbation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of hepatic microsomal cytochrome P-450 dependent monooxygenation activity by the antioxidant 3-tert-butyl-4-hydroxyanisole. 191 10

The adult respiratory distress syndrome (ARDS) is a devastating clinical illness characterized by refractory hypoxemia and high-permeability pulmonary edema. Reactive oxygen species such as hydrogen peroxide and hypochlorous acid may play a key role in the pathogenesis of the acute lung injury. Glutathione (GSH) is a tripeptide that is able to react with and effectively neutralize oxidants such as hydrogen peroxide and hypochlorous acid. The present study found that the alveolar epithelial lining fluid of patients with ARDS was deficient in total GSH compared to normal subjects (21.7 mumols +/- 7.8 mumols vs 91.8 mumols +/- 14.5 mumols; p = 0.002). In addition, if GSH was measured in unconcentrated bronchoalveolar lavage (BAL) fluid and indexed to total BAL protein, there was also a deficiency in patients with ARDS compared to normal subjects (0.004 +/- 0.003 nmol of GSH per microgram of total protein vs 0.026 +/- 0.005 nmol of GSH per microgram of total protein; p = 0.002). Since patients with ARDS are subjected to an increased burden of oxidants in the alveolar fluid, principally released by recruited neutrophils, this deficiency of GSH may predispose these patients to enhanced lung cell injury.
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PMID:Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome. 193

Glutathione deficiency induced in newborn rats by giving buthionine sulfoximine, a selective inhibitor of gamma-glutamylcysteine synthetase, led to markedly decreased cerebral cortex glutathione levels and striking enlargement and degeneration of the mitochondria. These effects were prevented by giving glutathione monoethyl ester, which relieved the glutathione deficiency, but such effects were not prevented by giving glutathione, indicating that glutathione is not appreciably taken up by the cerebral cortex. Some of the oxygen used by mitochondria is known to be converted to hydrogen peroxide. We suggest that in glutathione deficiency, hydrogen peroxide accumulates and damages mitochondria. Glutathione, thus, has an essential function in mitochondria under normal physiological conditions. Observations on turnover and utilization of brain glutathione in newborn, preweaning, and adult rats show that (i) some glutathione turns over rapidly (t 1/2, approximately 30 min in adults, approximately 8 min in newborns), (ii) several pools of glutathione probably exist, and (iii) brain utilizes plasma glutathione, probably by gamma-glutamyl transpeptidase-initiated pathways that account for some, but not all, of the turnover; thus, there is recovery or transport of cysteine moieties. These studies provide an animal model for the human diseases involving glutathione deficiency and are relevant to oxidative phenomena that occur in the newborn.
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PMID:Glutathione deficiency leads to mitochondrial damage in brain. 200 Mar 95

Glutathione content of mouse peritoneal macrophages markedly increased when they were exposed to insulting agents like sodium arsenite, cadmium chloride, and glucose/glucose oxidase which generates hydrogen peroxide. This increase was attributed to the induction of the cystine transport activity by these agents. The transport activity for other amino acids was not induced, but rather diminished by these agents. Heat shock treatment did not induce the cystine transport activity, nor did it augment glutathione. Since glutathione protects cells against the cytotoxic effects of these agents, the induction of the cystine transport activity constitutes a protective mechanism related to the stress caused by the agents. The protein component(s) for cystine transport may fall into the category of the stress protein.
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PMID:Enhancement of glutathione levels in mouse peritoneal macrophages by sodium arsenite, cadmium chloride and glucose/glucose oxidase. 201 83

Radiation interacts with biological systems to produce many types of molecular lesions. Much of the molecular damage is of little consequence with regard to cell killing. The lesions that are most likely to contribute to cell killing are DNA lesions produced by clusters of radicals. The formation of clusters of radicals is characteristic of ionizing radiation and accounts for its high efficiency as a cytotoxic agent. The mechanism by which these lesions kill cells is probably the formation of DNA double-strand breaks, ultimately resulting in chromosomal breaks. There is a possibility that some of the other types of molecular lesions produced by radiation may participate in more subtle mechanisms of cell damage. For instance, radiation induces a self-destructive process (apoptosis) in certain cell types, and the molecular lesions that initiate this process have not been identified. Glutathione (GSH) is a versatile protector. Several distinct mechanisms of radioprotection by GSH can be identified. These include radical scavenging, restoration of damaged molecules by hydrogen donation, reduction of peroxides and maintenance of protein thiols in the reduced state. Of these mechanisms, hydrogen donation to DNA radicals is probably the most important. Since competing reactions are very rapid, this mechanism requires a high concentration of GSH. Radioprotection by hydrogen donation to DNA radicals is not effective in oxygenated cells because the normal intracellular GSH concentration is not sufficient for effective competition with oxygen. Consequently, moderate depletion of GSH has no effect on the radiosensitivity of oxygenated cells. Under hypoxic conditions GSH becomes more competitive, and GSH depletion can markedly affect radiosensitivity. The radiosensitivity of hypoxic cells is most affected by GSH depletion in the presence of low concentrations of radiosensitizers. Since hypoxic cells are a characteristic feature of tumors, moderate depletion of GSH in combination with treatment with hypoxic cell radiosensitizers appears to be a promising strategy for selective tumor sensitization in radiation therapy. Oxidation of GSH can result in radiosensitization of both hypoxic and oxygenated cells. The mechanism of this effect appears to involve oxidation of protein thiols which are important for DNA repair. In principle, modification of DNA repair could have a greater impact on radiation therapy than modification of the number of lesions produced by radiation. However, a strategy for modification of GSH or protein thiol redox state in vivo has not yet been devised.
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PMID:Role of glutathione in the radiation response of mammalian cells in vitro and in vivo. 219 53


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