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)

In order to investigate the effects of growth and thyroid hormones on Ca2+ transport in liver mitochondria, Ca2+ release and other accompanying changes induced by t-butylhydroperoxide were measured in mitochondria from hypophysectomized and hormone-injected rats. Mitochondria from normal and hypophysectomized rats showed similar rates of Ca2+ uptake (40 nmol.min.-1 mg protein-1) and ruthenium red-insensitive release (3 nmol.min.-1 mg protein-1). However, the t-butylhydroperoxide (0.5 mM)-induced release of 90% of the added Ca2+ required 1027 +/- 98 and 560 +/- 35 s in the hypophysectomized and normal groups, respectively, and the difference was independent of Ca2+. The release was accompanied by a loss of membrane potential, large amplitude swelling, the oxidation of NAD(P)H and stimulation of respiration. At conditions of equivalent release rates, the rate and extent of swelling as well as the stimulation of respiration were lower in mitochondria from hypophysectomized rats than those in the normal group. These results were confirmed by electron microscopy and provided evidence for a dissociation between the release of Ca2+ and the increase of membrane permeability. The administration of bovine growth hormone and/or 3,5,3'-triiodo-L-thyronine to hypophysectomized rats decreased the Ca2+ release times by different degrees and thyroid hormone was more effective than growth hormone. Hypophysectomy doubled the GSH content and hormone injections decreased it and the Ca2+ release times in parallel. Indeed, a high degree of correlation (r = 0.96) was obtained between mitochondrial GSH and the release times from groups of differing hormone status. Differences in the groups in the time required for oxidation of 80-90% of GSH were correlated with the differences in the times for release of 90% Ca2+. Therefore, these results demonstrated that growth and thyroid hormones can alter both the hydroperoxide-induced Ca2+ release and the metabolism of GSH in liver mitochondria, suggesting that the two processes are related. It is proposed that the effects of these hormones on Ca2+ transport may result from the promotion of its efflux from mitochondria and its mobilization into the cytosol.
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PMID:Effects of hypophysectomy and administration of growth and thyroid hormones on the hydroperoxide-induced calcium release process and glutathione levels in rat liver mitochondria. 334 49

Hepatocyte cytotoxicity caused by substituted benzoquinones was associated with increased cytosolic Ca2+ concentration. p-Benzoquinone-induced hepatotoxicity was enhanced when the hepatocytes were loaded with Ca2+ by preincubation with ATP. A similar order of potency of the substituted benzoquinones in releasing Ca2+ from isolated mitochondria and inducing hepatocyte cytotoxicity was found; in decreasing order, this was 2-Br-, unsubstituted-, 2-CH3-, 2,6-(CH3O)2-, 2,6-(CH3)2-, 2,5-(CH3)2-, 2,3,5-(CH3)3-, and 2,3,5,6-(CH3)4-benzoquinones (duroquinone). The cellular products of quinone metabolism, hydroquinones and glutathione conjugates, did not cause mitochondrial Ca2+ release. Benzoquinone-induced mitochondrial Ca2+ release was preceded by GSH conjugate formation and NAD(P)H oxidation but followed by mitochondrial swelling. With duroquinone, a slow GSH and NADPH oxidation preceded Ca2+ release, but GSH oxidation did not occur with Se-deficient mitochondria lacking glutathione peroxidase activity. Cyanide-insensitive respiration was also observed with duroquinone but not with benzoquinone, suggesting that duroquinone undergoes redox cycling. GSH was depleted by both arylation and oxidation with 2,6-(CH3O)2-, 2,6-(CH3)2-, 2,5(CH3)2-, and 2,3,5-(CH3)3-benzoquinones. Benzoquinone concentrations that totally depleted GSH did not cause Ca2+ release until intramitochondrial NAD(P)H was oxidized. Ca2+ release was also prevented when NAD(P)H generation was stimulated by the presence of isocitrate or 3-hydroxybutyrate. This suggests that mitochondrial Ca2+ release is associated with NAD(P)H oxidation catalyzed by NADH dehydrogenase with benzoquinone or by the glutathione peroxidase-glutathione reductase system with duroquinone.
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PMID:Quinone toxicity in hepatocytes: studies on mitochondrial Ca2+ release induced by benzoquinone derivatives. 342 29

Ketoacid oxidation in rat liver mitochondria was very sensitive to t-butyl hydroperoxide (t-BuOOH). Furthermore, 2-oxoglutarate and pyruvate each enhanced t-BuOOH-induced oxidative stresses of mitochondria, such as oxidation of pyridine nucleotides and GSH, inhibition of respiration with the other NAD-linked substrates, and peroxidation of mitochondrial lipids. We provide evidence that the t-BuOOH and ketoacid-induced effects are due to the failure of supply of NADH by 2-oxoglutarate dehydrogenase, and report the inactivation of the dehydrogenase in mitochondria by simultaneous addition of 2-oxoglutarate and t-BuOOH. Using the purified enzyme, we confirmed that t-BuOOH-induced inactivation of 2-oxoglutarate dehydrogenase was enhanced by its substrate and thiamine pyrophosphate protected the dehydrogenase from the inactivation. In contrast, succinate-dependent oxidation of mitochondria was not only scarcely affected by t-BuOOH, but also succinate protected against inactivation of 2-oxoglutarate dehydrogenase by t-BuOOH in mitochondria.
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PMID:Inactivation of 2-oxoglutarate dehydrogenase in rat liver mitochondria by its substrate and t-butyl hydroperoxide. 358 93

The myotoxic and mutagenic aromatic amine, 1,2,4-triaminobenzene, has been shown to oxidise glutathione and reduced pyridine nucleotides in a cyclic reaction which generates both superoxide radical and hydrogen peroxide. It is suggested that the process is initiated by the triaminobenzene radical, formed by autoxidation of the amine. This, by mediating the one-electron oxidation of GSH and NAD(P)H, is able to establish a radical chain-reaction leading to the formation of GSSG and NAD(P)+. This reaction may be of significance in the pathogenesis of the toxic effects of 1,2,4-triaminobenzene, not only by forming reactive free-radicals but also by compromising cellular defences against oxidative attack.
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PMID:Oxidation of glutathione and reduced pyridine nucleotides by the myotoxic and mutagenic aromatic amine, 1,2,4-triaminobenzene. 359 37

5,5'-Dithiobis(2-nitrobenzoate) (DTNB) is reduced in mitochondrial suspensions to 5-mercapto-2-nitrobenzoate (MNB) by 3-hydroxybutyrate and isocitrate. Although most of the MNB produced is found in the suspension medium, there is also some within the particles. The amount of MNB found in these fraction varies with the DTNB concentration used and is much lower if mitochondrial glutathione (GSH) is depleted with 1-chloro-2,4-dinitrobenzene. If hydroxybutyrate is present, the reduction of DTNB is increased by ATP and oligomycin. The pellet contains only a little MNB and GSH but these are considerably elevated by antimycin and rotenone as well as by ATP and oligomycin. If isocitrate is present, the reduction of DTNB is greatly stimulated by valinomycin, triethyltin and, to a lesser extent, oligomycin. MNB in the pellet falls and GSH concentrations are unchanged. The results suggest that with hydroxybutyrate (an NAD reducing substrate), the rate of reduction of DTNB is limited by the rate of regeneration of GSH while with isocitrate (an NADP reducing substrate) it is limited by the rate of export of MNB from the matrix.
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PMID:The reduction of dithiobis(2-nitrobenzoate) by rat liver mitochondria. 394 94

The pathway of oxidation of picolinamide (pyridine-2-carboxamide) by a Gram-negative rod has been elucidated. Under conditions of high pH, restricted aeration and high substrate concentration, whole cells released 2,5-dihydroxypyridine into culture supernatants. Sodium arsenite at 5mm caused whole cells to accumulate 6-hydroxypicolinate, and, at 1mm, pyruvate, in culture media. Whole cells oxidized picolinamide, picolinate, 6-hydroxypicolinate, maleamate and maleate without lag. Cell-free extracts converted picolinamide into picolinate, and hydroxylated picolinate to 6-hydroxypicolinate. The hydroxylase was particulate, but could be solubilized by ultrasonic treatment; it required NAD(+) for activity, and did not require molecular oxygen. 2,5-Dihydroxypyridine was converted into maleamate and formate by an oxygenase requiring GSH and Fe(2+). Maleamate was deamidated to maleate, and maleate isomerized to fumarate, by unsupplemented extracts.
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PMID:The bacterial oxidation of picolinamide, a photolytic product of Diquat. 434 98

1. cis-Benzene glycol dehydrogenase was purified to a homogeneous state from a species of Pseudomonas grown with benzene as the major carbon source. 2. The enzyme was specific for the cis-isomer of its substrate and required NAD(+) as hydrogen acceptor. 3. Partial inactivation of the enzyme, which was observed during purification, could be reversed by the addition of Fe(2+) and GSH. 4. A molecular weight of 440000 was calculated from data obtained by sedimentation-velocity and diffusion analysis in the ultracentrifuge. Sodium dodecyl sulphate polyacrylamide-gel electrophoresis indicated a subunit of molecular weight 110000. 5. p-Chloromercuribenzoic acid and 1,10-phenanthroline were shown to inhibit the enzyme.
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PMID:The metabolism of benzene by bacteria. Purification and some properties of the enzyme cis-1,2-dihydroxycyclohexa-3,5-diene (nicotinamide adenine dinucleotide) oxidoreductase (cis-benzene glycol dehydrogenase). 436 37

Spectrophotometric assay methods are described for glutathione synthetase, gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase of erythrocytes. The contents of these enzymes in normal human erythrocytes are reported. Erythrocyte glutathione synthetase is inhibited by ADP; this inhibition is competitive with respect to ATP. gamma-Glutamylcysteine synthetase is subject to feedback inhibition by GSH, and is also inhibited by NADH, and to a lesser extent by NAD(+) and NADPH. This enzyme is irreversibly inactivated by cysteamine.
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PMID:Studies in the enzymology of glutathione metabolism in human erythrocytes. 438 10

1. beta-Hydroxy-beta-methyl[3-(14)C]glutaryl-CoA is efficiently incorporated into rubber on incubation with Hevea brasiliensis latex, and the incorporation is diminished in the presence of unlabelled mevalonate. beta-Hydroxy-beta-methylglutaric acid is not utilized for rubber synthesis, but inhibits the formation of rubber from beta-hydroxy-beta-methylglutaryl-CoA. 2. The incorporation of beta-hydroxy-beta-methylglutaryl-CoA into rubber is stimulated equally by NADP(+) and NADPH and less so by NAD(+) and NADH. ATP is slightly stimulatory and CoA is inhibitory. 3. beta-Hydroxy-beta-methylglutaryl-CoA reductase is concentrated in the sediment (bottom fraction) formed by centrifuging latex at low speed and the enzyme is unstable in the absence of cysteine or GSH. The formation of NADPH takes place in the latex serum. 4. There is a marked seasonal variation in the extent of beta-hydroxy-beta-methylglutaryl-CoA incorporation into rubber in latex, but mevalonate incorporation is relatively constant. This observation, together with the finding that beta-hydroxy-beta-methylglutaryl-CoA reduction is the rate-limiting step in the formation of rubber from beta-hydroxy-beta-methylglutaryl-CoA, suggests that the conversion of beta-hydroxy-beta-methylglutaryl-CoA into mevalonate is of importance in the regulation of rubber synthesis. 5. Evidence suggesting that beta-hydroxy-beta-methylglutaryl-CoA lyase is present in H. brasiliensis latex has been obtained.
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PMID:Th biosynthesis of rubber from beta-hydroxy-beta-methylgluarylcoenzyme A in Hevea brasiliensis latex. 439 Feb 12

Human lung cancers of distinct histology exhibit different responses to radiation therapy in vivo. For examination of the basis of this phenomenon, the radiation survival curves and levels of relevant enzymes were determined in 16 lung cancer cell lines derived from tumors of different histology. These included lines from 5 adenocarcinomas, 7 small cell tumors, 3 variant small cell tumors, and 1 large cell tumor. These findings were compared to those obtained with the use of a normal skin fibroblast cell line. Whether cloned in liquid culture or soft agarose, cell lines had similar radiation survival curves. These curves were consistent with the apparent in vivo radiation responsiveness of the tumors. Although considerable heterogeneity in radiation survival curves was observed among the cell lines, cells from large cell lines and small variant lines had pronounced shoulders and extrapolation numbers (n) from 5.6 to 14. In contrast, cells from small cell lines and adenocarcinoma cell lines were more "sensitive" (-n values of 1-3.3). In these cell lines, levels of DNA polymerase beta, glutathione (GSH), GSH transferase, GSH reductase (NAD(P)H), gamma-glutamyltransferase did not correlate with radiation parameters of sensitivity. DNA polymerase beta and GSH levels were, however, higher than those in a line of normal skin fibroblasts. These cell lines may be useful in identifying the basis of the variable responsiveness of human lung cancer cells to ionizing radiation.
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PMID:Heterogeneity in the radiation survival curves and biochemical properties of human lung cancer cell lines. 614 44


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