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)

Methylxanthines (MX) inhibit cell division in sea urchin and clam eggs. This inhibitory effect is not mediated via cAMP. MX also inhibit respiration in marine eggs, at concentrations which inhibit cleavage. Studies showed that no changes occurred in ATP and ADP levels in the presence of inhibitory concentrations of MX, indicating an extra-mitochondrial site of action for the drug. Subsequent studies revealed decreased levels of NADP+ and NADPH, when eggs were incubated with inhibitory concentrations of MX, but no change in levels of NAD+ and NADH. MX did not affect the pentose phosphate shunt pathway and did not have any effect on the enzyme NAD+ -kinase. Further studies showed a marked inhibitory effect on the glutathione reductase activity of MX-treated eggs. Reduced glutathione (GSH) could reverse the cleavage inhibitory effect of MX. Moreover, diamide, a thiol-oxidizing agent specific for GSH in living cells, caused inhibition of cell division in sea urchin eggs. Diamide added to eggs containing mitotic apparatus (MA) could prevent cleavage by causing a dissolution of the formed MA. Both MX and diamide inhibit a Ca2+-activated ATPase in whole eggs. The enzyme can be reactivated by sulfhydryl reducing agents added in the assay mixture. In addition, diamide causes an inhibition of microtubule polymerization, reversible with dithioerythritol. All experimental evidence so far suggests that inhibition of mitosis in sea urchin eggs by MX is mediated by perturbations of the in vivo thiol-disulfide status of target systems, with a primary effect on glutathione levels.
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PMID:Effects of caffeine and other methylxanthines on the development and metabolism of sea urchin eggs. Involvement of NADP and glutathione. 1 15

The uptake of alpha-methyl-D-glucoside by slices of renal cortex was compared in normal and alloxan diabetic rabbits. Alloxanized rabbit tissue showed significantly higher levels of sugar accumulation than normal tissue. Diamide, which is known to oxidize intracellular glutathione (GSH), inhibited the uptake of alpha-methyl-D-glucoside by renal cortical slices. GSH stimulated sugar uptake and was also capable of reversing the inhibition of sugar accumulation caused by diamide. Mercaptoethanol and dithiothreitol, which are commonly used thiol compounds, were not as effective as GSH in stimulating sugar uptake. The level of GSH found in normal and alloxan diabetics rabbit kidneys shows a slightly decreased cortical GSH content in alloxanized animals. One can conclude that GSH participates in sugar uptake in kidney slices from both diabetic and normal rabbits.
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PMID:alpha-Methyl-D-glucoside uptake in renal cortical slices of normal and alloxan diabetic rabbits. 9 22

Diamide directly added to renal cortical slices inhibits the uptake of amino acids. Steady-state kinetic analysis indicates an inhibition of alpha-amino acid influx without effect on efflux. The effect could be reversed by addition of pyruvate to the incubation medium. Although there was a good correlation of the transport effect of diamide with its ability to decrease cellular reduced glutathione concentration, there did not appear to be a necessary connection between them. This was shown by the fact that renal cortical slices stored at 4 degrees C have no alteration in amino acid uptake despite the fact that GSH concentration is as low as that seen with diamide. Diamide was shown to have a direct effect on the uptake of glycine by isolated renal brush border membrane vesicles.
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PMID:The effect of diamide on amino acid transport by rat renal cortex slices. 49 93

The role of reduced glutathione (GSH) on platelet functions was investigated utilizing thiol oxidizing agent, "diamide". Diamide reacted rapidly with GSH in platelets, but not with protein thiols. Platelets treated with diamide showed inhibition of platelet aggregation induced by ADP, epinephrine and collagen in a concentration dependent manner. Clot retraction was grossly inhibited by diamide. Platelet interaction with polymerizing fibrin was examined by the method of Niewiarowski et al. (1972). There was no interaction obeserved between diamide-treated platelets and polymerizing fibrin. Ultrastructural observation of clots formed in the presence of diamide also showed no direct contact between platelets and fibrin strands. Platelets retained their granular contents, but showed loss of microtubules and dilatation of open canalicular system. Our findings may further support the idea that GSH plays an important role on platelet functions.
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PMID:Role of reduced glutathione on platelet functions. 54 37

Concentrations of insulin and chemical agents (H2O2, vitamine K-5) which stimulate hexose transport in fat cells do not alter the cellular levels of glutathione (reduced form; GSH). Diamide, another agent used in studies of insulin action, markedly reduces GSH levels and increases the movement of sugar into the cell. However, unlike insulin, H2O2 or vitamin K-5, diamide causes a change in the permeability of fat cells that allows entry of compounds (insulin, sucrose, L-glucose) which are normally excluded by the plasma membrane. Moreover, the accelerated rate of methylglucose uptake produced by diamide treatment is not inhibited by cytochalasin B, an agent that blocks basal and insulin-stimulated methylglucose transport. These results indicate that diamide does not cause a stimulation of the glucose transport system and should not be used (or used with caution) in transport studies. Furthermore, oxidation of GSH does not appear to be necessary for the stimulation of hexose transport in adipocytes by insulin, H2O2 or vitamin K-5.
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PMID:Effects in adipocytes of diamide on GSH levels, glucose uptake and cell integrity. 71 90

Taurine, a naturally found beta-amino acid, is inert in rat renal cortex slices. Its active accumulation by slices is abolished by anaerobiosis, a strongly acidic media or the removal of Na+. Concentration-dependent uptake studies reveal more than one taurine carrier: the apparent Km value for uptake below 1.1 mM is 0.4 mM and the apparent Km value above 1.1 mM is 14.5 mM. Of all amino acids tested only beta-alanine, another beta-compound, inhibited uptake. The oxidizing agent diamide was used to lower the concentration of GSH in rat cortex slices. The ability to accumulate taurine by the low Km system was decreased in diamide-treated slices, but not by the high Km system. Diamide was found to greatly augment efflux of taurine taken up from lower concentrations but not from higher concentrations. GSH in the media prevented this diamide-induced inhibition of uptake and enhanced efflux at lower taurine concentrations. A possible mechanism of diamide inhibition of uptake is that intracellular GSH depletion leads to greatly enhanced efflux of taurine, thus preventing uptake.
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PMID:Heterogeneity of the beta-amino-preferring transport system in rat kidney cortex. Differential influence of glutathione oxidation. 85 33

The uptake of alpha-methyl-D-glucoside was stimulated in slices of rat kidney cortex by pretreatment with reduced glutathione. Diamide, an oxidizind agent with high specificity for GSH, caused an inhibition of alpha-methyl-D-glucoside uptake. These effects appeared to be related specifically to GSH, since dithiothreitol and mercaptoethanol did not increase alpha-methyl-D-glucoside uptake, and were not as effective as GSH in reversing the effects of diamide. GSH and diamide had no effect on the uptake of another sugar analog, 3-O-methylglucose, which is not actively transported. Kinetic studies indicated that GSH increased the apparent V without affecting K-m. The results are discussed in terms of the possible role of GSH in the process of sugar transport.
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PMID:The effect of diamide and glutathione on the uptake of alpha-methyl-D-glucoside by slices of rat kidney cortex. 112 Jan 58

Unstimulated normal human blood platelets were treated with azodicarboxylic acid bis(dimethylamide) (diamide), a thiol-oxidizing agent. Oxygenated arachidonic acid (AA) metabolites, malondialdehyde (MDA), and tocopherols were then quantified by high-performance liquid chromatography (HPLC). Diamide treatment partially decreased the amount of reduced glutathione (GSH) content and induced a subsequent decrease in peroxidase activity. However, formation of 12-hydroxy-eicosatetraenoic acid (12-HETE), the end-product of lipoxygenation of AA, increased. Formation of MDA, a marker of overall lipid peroxidation, was also enhanced. Furthermore, platelet alpha-tocopherol, but not gamma-tocopherol, significantly decreased. These results indicate that enhanced "basal" lipoxygenase activity, as a marker of specific AA oxygenation, may be linked to decreased platelet antioxidant status.
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PMID:Decrease in platelet reduced glutathione increases lipoxygenase activity and decreases vitamin E. 176 13

Reactive O2 species appear to be generated both during hypoxia and at reoxygenation, but it has not been established whether these species interact with heart tissue and cause injury. Oxidative changes were evaluated in isolated rat heart perfused with Krebs-Henseleit medium containing 10 mM glucose and 2.5 mM calcium. After 5-10 min hypoxia, tissue glutathione (GSH) decreased while glutathione disulfide (GSSG), protein carbonyls, and thiobarbituric acid reactive substances (TBARS) increased compared with controls. Similarly, sarcolemmal and sarcoplasmic reticular Ca-ATPase activity (an enzyme susceptible to oxidative inactivation) decreased in response to 10 min hypoxia. These changes were more pronounced after 60 min of hypoxia when protein-GSH mixed disulfides were also increased. There were no further oxidative changes after 4 min reoxygenation when the release of lactate dehydrogenase (LDH) was maximal. Myocardial protein thiol and alpha-tocopherol contents were not significantly changed by either hypoxia or reoxygenation. Mitochondria also exhibited oxidative changes but with more pronounced increases in GSSG and mixed disulfides. There was no change in GSH or GSSG efflux into the coronary effluent during hypoxia, although, in parallel with LDH release, both increased after reoxygenation. Diamide (200 microM), t-butylhydroperoxide (20 microM), or purine (2.3 mM) + xanthine oxidase (0.01 U/ml) were infused for 10 min. Except for large diamide-induced changes in protein thiols and mixed disulfides, the magnitude of the changes produced by these oxidants was similar to those produced by hypoxia. These data show that changes consistent with oxidative processes occur in whole heart and mitochondria in response to hypoxia. The absence of marked signs of oxidation at reoxygenation suggest that enzyme release at this time is unrelated to oxidative stress.
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PMID:Oxidative changes in hypoxic rat heart tissue. 203 61

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


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