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)

Insulin is known to stimulate intracellular H2O2 production in rat adipocytes. This H2O2 could in turn stimulate the pentose phosphate cycle by oxidizing GSH and shifting the redox state of the cells. However, insulin had no effects on cell GSH content or GSSG in buffer other than as related to changes in medium glucose. On the contrary, in the presence of an active pentose phosphate cycle, insulin tended to reverse the fall in glutathione content induced with the catalase inhibitor 3-amino-1,2,4-triazole, the oxidant t-butyl hydroperoxide and the sulfhydryl blocker N-ethylmaleimide. It was also found that insulin-stimulated H2O2 production could be blocked under conditions in which the effect of the hormone on the pentose phosphate cycle persisted. These results suggest that stimulation of the pentose phosphate cycle by insulin is not related to increased H2O2 generation, rather that activation of the pentose phosphate cycle by the hormone may provide NADPH for regeneration of depleted GSH.
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PMID:The effect of insulin-stimulated pentose phosphate cycle activity on cellular glutathione content in rat adipocytes. 675 59

The stationary dependence of the rate of pentose cycle in erythrocytes measured by CO2 production on the degree of glutathione reduction typical for the pentose cycle was established. The steady-state rate of oxidation from the physiological to maximal values was generated by the addition of tretbutylhydroperoxide, a substrate of the glutathione peroxidase reaction, to erythrocyte suspension at a constant rate. The steady-state rate of CO2 production was correlated with the rates of oxidant addition throughout the experiment. The parameters of the pentose cycle reactions under conditions when the maximal rate of the pentose cycle and glutathione pool (GSH+2 GSSG) are taken for 100%, coincided for all donors tested. The increase in the rate of pentose cycle from 0 to 60% of the maximal one had practically no effect on the concentration of GSH, which was as high as 90% of the overall glutathione pool, thus indicating a high stabilization degree of GSH (stabilization coefficient was about 15). A further increase of the rate up to maximal values resulted in a rapid fall of the GSH level down to 0. The data obtained support the previously described mathematical model for regulation of glutathione metabolism. The GSSG liberation from the erythrocytes was shown to be directly proportional to the stationary intracellular concentration of GSSG; the transport rate constant varied in different donors from 0.15 up to 0.6(-1). The increase of oxidation rates up to maximal values, when GSSG concentration was approximated to the glutathione pool leads to a reversible decrease of GSSG concentration, which destroys the steady-state equilibrium of the pentose cycle.
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PMID:[Dependence of the rate of the pentose cycle reactions on the degree of glutathione reduction in erythrocytes]. 678 78

In isolated rat pancreatic islets, glucose (5.6, 11.1, and 16.7 mM) significantly increased reduced glutathione (GSH) and decreased oxidized glutathione (GSSG) levels in a dose-related manner. This was paralleled by a concomitant increase of NADPH and a decrease of NADP. The change of the GSH level occurred as quickly as one minute after addition of glucose. Exogenous insulin (200, 400, and 800 microU/ml) significantly decreased islet GSH levels in the presence of 5.6 and 16.7 mM glucose and significantly inhibited the insulin-releasing effect of the thiol reagent parachloromercuribenzoate (p-CMB) and tolbutamide. These data, together with earlier observations, suggest that GSH levels in pancreatic islets are increased by glucose and decreased by exogenous insulin via their effects on the pentose phosphate shunt and NADPH. Our results are compatible with the hypothesis that glucose and exogenous insulin, by modifying the redox state of the NADPH/NADP and GSH/GSSG systems, modulate the sensitivity of the beta-cell to the insulin-triggering actions of glucose, p-CMB, and tolbutamide.
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PMID:Islet glutathione and insulin release. 700 64

Paraquat (1 mM), when added to isolated haemoglobin-free perfused rat liver, leads to an increase of intracellular mixed disulphides from 1.3 mumole GSH equivalents per g wet weight in the controls to 2.5 mumole/g. This raises the proportion of mixed disulphides to total glutathione equivalents from about 0.2 at the beginning of the perfusion to about 0.4. The mixed disulphides are predominantly protein-bound, with low molecular weight compounds being quantitatively negligible. The content of intracellular glutathione disulphide (GSSG) is increased from 17 nmole/g in the controls to 38 nmole/g in the presence of paraquat. In addition, there is an increased rate of release of GSSG into the extracellular (biliary) space, reported previously. It is suggested that, in a reaction catalysed by thioltransferase(s), the rise in GSSG is correlated with the rise in mixed disulphides (reaction 1). Occupancy of potential cellular mixed disulphide sites is about 1/2 in the controls, and rises to about 2/3 in the presence of paraquat. THe ratio of cellular contents, NADPH/NADP+, is decreased from 5.1 in the controls to 2.3 in the presence of paraquat, while the sum of NADPH plus NADP+ remains unaltered. The perturbation in the glutathione status may be related to metabolic effects such as the stimulation of the pentose-phosphate pathway activity, and possibly also to the expression of toxic effects.
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PMID:Increase in hepatic mixed disulphide and glutathione disulphide levels elicited by paraquat. 709 55

Generation of hydrogen peroxide in adipocyte plasma membrane and its intracellular metabolism and regulatory role have been shown by Mukherjee and co-workers to be a major effector system for insulin [Fedn Proc. 35, 1694 (1976); Archs Biochem. Biophys. 184, 69 (1977); Biochem. Pharmac. 27, 2589 (1978); Fedn Proc. 37, 1689 (1978); and Biochem. Pharmac. 29, 1239 (1980)]. The possible involvement of this mechanism in the action of structurally similar polypeptides having some insulin-like metabolic effects was investigated. The beta-subunit of nerve growth factor (2.5 S NGF, mol. wt 13,500) which has a striking structural homology with proinsulin and has been reported to exert certain insulin-like metabolic effects in its own target tissues (e.g. growing neurites and sympathetic ganglia), and the insulin-derived polypeptides, desalanine-insulin and desoctapeptide-insulin, as well as proinsulin, were examined for their effects on rat adipocytes, employing the technique of formate oxidation. Both NGF and proinsulin caused increased [14C]formate oxidation, showing similar intrinsic activities, up to a maximum of 140-160% of the basal rate; insulin increased the rate to 190-210% of the basal rate. The relative potencies of the hormones toward H2O2 formation and stimulation of the pentose phosphate pathway activity were: insulin (EC50: 2.5 x 10(-11) M), desalanine-insulin (EC50: 2.5 x 10(-10) M), proinsulin (EC50: 8 x 10(-9) M), and NGF (EC50: 10(-9) M). The biologically inactive derivative, desoctapeptide-insulin, did not stimulate glucose oxidation, although it caused a small increase in formate oxidation, with an EC50 of 5 x 10(-7) M, indicating a suboptimal level of H2O2 formation in the elevation of the hexose monophosphate shunt activity. 3-Amino-1,2,4-triazole (50 mM), which irreversibly decomposes the peroxidatic compound II of the catalase: H2O2 complex, inhibited formate oxidation to a greater extent in the hormone-treated cells than in the control cells, whereas sodium azide, an inhibitor of the hemoprotein, catalase, completely inhibited it. The abilities of the polypeptides to stimulate H2O2 formation correlated with their abilities to promote lipogenesis from [U-14C]-D-glucose, as expected of insulin. The cellular GSH/GSSG ratio increased concomitantly with the stimulation of glucose oxidation via the shunt, indicating a tight coupling between these processes. The results confirm that the hydrogen peroxide production is a common basis of the metabolic actions of growth-promoting polypeptide hormones or mitogens beyond their respective receptors.
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PMID:Similar activities of nerve growth factor and its homologue proinsulin in intracellular hydrogen peroxide production and metabolism in adipocytes. Transmembrane signalling relative to insulin-mimicking cellular effects. 715 Mar 45

A mathematical model of glycolysis in human erythrocytes for the interaction between the Embden-Meyerhof and the pentose phosphate pathways has been developed. The characteristic surfaces, i. e. interdependencies between the rates of metabolite flows in both pathways and ATP and NADPH concentrations have been calculated. The model obtained is well correlated with the experimental data on glycolysis characteristic at low rates of the pentose phosphate pathway reactions. The model suggests that NADPH and GSH concentrations should be stabilized. At ATP and NADPH concentrations close to the physiological ones the Embden-Meyerhof and pentose phosphate pathways function practically independently. When the NADPH concentration is decreased below 80% of the physiological value, the system ceases to stabilize the ATP concentration. In its turn, a decrease of ATP concentration results in a corresponding decrease of the maximal rate of the pentose phosphate pathway.
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PMID:[Interaction of the Embden-Meyerhof pathway and hexose monophosphate shunt in erythrocytes]. 728 86

The stability of free glucocerebrosidase activity has been compared with the stability of glucocerebrosidase entrapped in hemolyzed, resealed erythrocytes. Encapsulation markedly stabilizes the enzyme, partly by providing an environment with a high protein concentration. In addition, in the presence of glucose, enzyme activity and GSH content remain constant, but in its absence, enzyme activity and GSH levels fall, indicating the existance of an additional, metabolically linked protective mechanism. Since the free enzyme is inactivated by p-CMB and is protected by DTT, it is likely that GSH generated by the pentose phosphate pathway protects essential sulfhydryl groups of glucocerebrosidase.
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PMID:Enhanced stability of erythrocyte-entrapped glucocerebrosidase activity. 741 57

In 14 beagle dogs, paraquat was infused in fractional doses to produce pulmonary fibrosis while avoiding fatal liver and kidney lesions. Activity of the three enzymes of the pentose pathway: glucose-6-phosphate dehydrogenase (G-6-PDH), glutathione reductase (GR) and glutathione peroxidase (GSH Px), which supply reduced equivalents against oxidant agents, were measured in the mediastinal lobe of the lung. After a single low dose (2-3 mg/kg body weight), GR and GSH Px activities were reduced. After repeated paraquat doses, pentose pathway enzyme activities were higher than after a single low dose; however, they did not significantly exceed the normal values as determined in control dogs. The activities of G-6-PDH, GR and GSH Px correlated with the total paraquat dose and with the extent of pulmonary fibrosis measured with an electronic image analyzer. The activity of pulmonary lactate dehydrogenase, which was also reduced after a single low dose of paraquat, did not show the same correlations.
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PMID:Pentose pathway in pulmonary fibrosis due to chronic paraquat poisoning. 744 87

The effects of glucose concentration on D-glucose oxidation and reduced nicotinamide adenine dinucleotide phosphate (NADPH) supply were studied during exposure of cultured human umbilical vein endothelial cells to hydrogen peroxide (H2O2). The activation of glucose oxidation via the pentose phosphate pathway (PPP), induced by exposure of cells to 200 mumol/l H2O2 for 1 h, was reduced by 50% (P < 0.01) in cells cultured for 5-7 days in 33 mmol/l D-glucose (HG) versus those cultured in 5.5 mmol/l D-glucose without (NG) or with (HR) 27.5 mmol/l D-raffinose. The intracellular NADPH content in HG cells, but not in NG or HR cells, was decreased by 42% (P < 0.01) by exposing cells to 200 mumol/l H2O2. The decrease in NADPH was dependent on D-glucose concentration in the medium and was prevented in glutathione (GSH)-depleted cells. The latter observation suggests that the decrease in NADPH is associated with activation of the GSH redox cycle. In the presence of 200 mumol/l H2O2, lactate release into the medium, NADH/NAD ratio, and phosphofructokinase activity in HG cells were 56, 53, and 68% greater, respectively, than in the NG group, which indicates that inhibition of glycolysis by H2O2 is less marked in the HG group compared with NG group. These results indicate that activation of the PPP was impaired in endothelial cells cultured under conditions of high-glucose and oxidative stress, resulting in a decreased supply of NADPH to various NADPH-dependent pathways, including the GSH redox cycle.
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PMID:Impaired activation of glucose oxidation and NADPH supply in human endothelial cells exposed to H2O2 in high-glucose medium. 772 9

Lens proteins are long lived proteins with those in the center of the lens predating the birth of the individual. As a result, they are subject to a host of modifications and damage through a variety of mechanisms. Two such modifications have been proposed as primary events which could cause conformational changes potentiating further modifications. These are non-enzymatic glycation and mixed disulfide formation. Human lenses accumulate protein-thiol mixed disulfides of three kinds throughout the lifespan. The presence of one of these, protein-glutathione (PSSG) mixed disulfide has been shown to be intimately involved in protein aggregation. We have utilized ex vivo lens culture and in vitro incubations of purified gamma-crystallin to evaluate the following hypotheses. A) Lenses cultured with a high sugar media will form higher mixed disulfide levels than controls; B) glycation of lens proteins will be dependent on initial mixed disulfide level. Xylose levels in the cultured lens rise rapidly (to 23 mM by 4 h), and the level of glycation after one week is elevated 6-7% over control values. Mixed disulfide levels are also substantially increased but not more than for lenses cultured in control media. gamma-Crystallin modified with 0, 1, or 5 equivalents of GSH was differentially glycated by radioactive fructose. The amount of fructose bound by the protein was found to be inversely related to the extent of mixed disulfide formation. These results indicate that 1) protein modification of one kind may influence further modifications of other types; 2) glycation of lens proteins has no effect on mixed disulfide formation in this system; 3) the sulfhydryl status of lens proteins can affect the potential for protein glycation.
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PMID:The culture of rat lenses in high sugar media: effect on mixed disulfide levels. 776 4


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