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Query: UMLS:C1260386 (GSH)
 38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies had shown that administration of streptozotocin to rats produces both diabetes and hemolysis and that both could be ameliorated by prior injections of diazoxide. Thus, it appeared pertinent to define the effect of streptozotocin on the red cell. In the present studies, streptozotocin administered in vivo to rats produced a rapid fall in red-cell-reduced glutathione. This effect was duplicated in vitro in incubated human red cells. Furthermore, it was demonstrated that glucose loading prior to bleeding modified the in-vitro red-cell GSH response to streptozotocin and that preincubation of red cells from fasted individuals with glucose, nicotinamide, and epinephrine (but not nicotinic acid) protected against the subsequent effect of streptozotocin on RBC GSH. The pattern of the RBC GSH response under each of these conditions is that which occurs in response to challenge with an oxidant, that is, with appropriate protection, oxidation stress produces an acute rise rather than falll in gsh. further, when glucose was present through both preincubation and test periods (i.e., in presence of streptozotocin) a third pattern of GSH response was observed--no change. The data are compatible with the postulate that the cytotoxic action of streptozotocin is dependent, in part, on an oxidant effect, and that glucose may protect through at least two mechanisms, that adrenergic stimulation can enhance protective mechanisms against redox insults and so contribute to maintenance of cell viability.
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PMID:Effect of streptozotocin on red-blood-cell-reduced glutathione: modification by glucose, nicotinamide, and epinephrine. 13 Feb 72

The decrease in the level of liver glutathione (GSH) in endotoxin-treated mice was in part due to formation of glutathione disulfide (GSSG). An electron-generating system (EGS) had no effect when incubated with soluble liver extracts from normal controls but resulted in recovery of GSH amounting to 25% in endotoxin-treated animals. Incubation in the absence of the EGS caused a decline of 16% in the GSH in extracts from normal animals compared with a 50% decrease in endotoxin-treated animals. Exclusion of nicotinamide adenine dinucleotide phosphate (NADP) from the EGS resulted in a slight decline in the GSH of the extract from the normal controls but 25% for the endotoxin-treated animals. Reduction of exogenous GSSG by the liver extracts required that exogenous NADP be added to ghe incubation mixtures.
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PMID:Liver glutathione and glutathione reductase response of endotoxin-treated mice. 23 13

A simple and rapid colorimetric method for the assay of erythrocyte and plasma glutathione reductase (GR) activity is described. The method is based on the colorimetric measurement of reduced glutathione (GSH) (1) produced when the enzyme is incubated with oxidised glutathione (GSSG) in the presence of either reduced nicotinamide adenine dinucleotide (NADH) or reduced nicotinamide adenine dinucleotide phosphate (NADPH). Results of investigations on the effects of substrate and coenzyme concentrations, pH, EDTA, sodium/potassium chloride, and time, on enzyme activity are presented. Erythrocyte and plasma NADH-GR and NADPH-GR activities in 100 healthy blood donors, and 85 cord blood samples and plasma NADH-GR and NADPH-GR levels in patients with various disease conditions are given.
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PMID:A new colorimetric method for the determination of NADH/NADPH dependent glutathione reductase in erythrocytes and in plasma. 23 82

A clinical screening procedure was developed for estimating glutathione peroxidase (GSH-Px) activity and selenium status in the blood of dairy and beef cattle. The test is based on the rate of defluorescence under long waveform UV irradiation of reduced nicotinamide adenine dinucleotide phosphate in a coupled enzyme reaction involving glutathione reductase. Defluorescence rates were significantly correlated with blood GSH-Px activity and blood selenium concentrations as determined by conventional laboratory procedures. Blood selenium concentrations and blood GSH-Px activity in several herds were compared with the selenium content of the complete ration consumed to establish reference or base-line values for these blood characteristics under field conditions. The GSH-Px screening procedure provides rapid results, is relatively inexpensive, and appears to be useful in differentiating between the reference values and grossly inadequate selenium status in cattle.
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PMID:Reference values for a field test to estimate inadequate glutathione peroxidase activity and selenium status in the blood of cattle. 47 23

In vivo spin trapping of radical metabolites has become a promising tool in understanding and predicting toxicities caused by different xenobiotics. However, in biological systems radical adducts can be reduced to electron paramagnetic resonance (EPR)-silent hydroxylamines. To overcome this difficulty, different procedures for reoxidation of the reduced radical adducts were systematically investigated and some metabolic inhibitors of nitroxide reduction were tested. As a test system, carbon tetrachloride (CCl4), a known hepatotoxic substance, was used. CCl4 is metabolized by liver to .CCl3 and, in the presence of the spin trap phenyl N-t-butylnitrone (PBN), forms the PBN/.CCl3 and PBN/.CO2- radical adducts. These radical adducts were measured in the bile using electron paramagnetic resonance after administration of CCl4 and PBN to the rat. We have shown that these radical adducts were reduced to the corresponding hydroxylamines in vivo, since immediately after the collection of bile only traces of the radical adducts could be detected, but after oxidation by different procedures such as bubbling with oxygen, addition of mild oxidant potassium ferricyanide or autoxidation the EPR spectra intensity increases, indicating that the hydroxylamines had been re-oxidized back to nitroxides. The collection of bile into plastic Eppendorf tubes containing the sulfhydryl reagent N-ethylmaleimide (NEM) or the enzyme ascorbate oxidase did not increase the intensity of the spectra significantly, demonstrating that neither reduction by reduced glutathione (GSH) nor ascorbic acid occurred ex vivo. However in the presence of NEM faster re-oxidation was observed. A new radical adduct that was not observed previously in any in vivo experiment and which exhibited 13C hyperfine coupling was detected when the rats were injected with 13CCl4. We have proven that this is the same adduct detected previously in vitro in microsomal incubations of CCl4, PBN, GSH, and reduced nicotinamide adenine dinucleotide phosphate (NADPH). As a general rule, we have shown that a variety of oxidation procedures should be tried to detect the different radical adducts which are otherwise not observable due to the in vivo reduction of radical adducts.
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PMID:Inhibition of radical adduct reduction and reoxidation of the corresponding hydroxylamines in in vivo spin trapping of carbon tetrachloride-derived radicals. 132 96

The coenzymatic capacity of NAD+ decreases by exposing it to the action of ascorbic acid--Cu(II) system, a generator of free radicals. The participation of the radicals in degrading NAD+ depends on the nature of the buffer, incubation medium pH, temperature, incubation time. Thiourea, IK, GSH, cysteine, mannitol, albumine reduce to different extents the noxious action of the radicals. The decrease of the coenzymatic function of NAD+ is caused by the break of esther and anhydride links, evidenced by releasing th cian-sensitive compounds--nicotinamide riboside and nicotinamide ribonucleotide. Also the presence of ortophosphate was demonstrated.
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PMID:The action of the couple ascorbic acid--Cu(II) on NAD(+)-coenzymatic function. 182 2

Human gingival fibroblast cultures were used to investigate the role of cellular thiol redox status in the mitogenic response. Increases in intracellular Ca2+ and cell cycle progression beyond G1 were followed as parameters of cellular mitogen-induced responses. Ethionine provided a G1 stage synchronization and altered the cellular redox poise as measured by the ratio NAD(P)H/NAD(P)+. Cultures harvested immediately after the 6 day ethionine low-serum synchronization showed a significant oxidation of their redox poise. Synchronized cultures, which were also glutathione (GSH) depleted, still showed an oxidized redox poise and significantly reduced GSH levels following a 24 hr incubation in drug-free, rich medium. Cellular reduced nicotinamide nucleotide levels correlated strongly (r = 0.995) with capacity to mobilize intracellular Ca2+ in response to basic fibroblast growth factor (bFGF). The sustained mitogenic response, as determined by cell cycle progression beyond G1, was also found to be interrelated with the cellular thiol redox status. Following a 24 hr recovery incubation in serum-rich medium, formerly synchronized cultures showed a rebound of their redox poise to a more reduced state and significant cell cycle progression beyond G1. In contrast, synchronized, GSH-depleted cultures did not progress and showed population distributions similar to those of cultures harvested immediately postsynchronization. Upon recovery of cellular GSH and reduced nicotinamide nucleotide levels, formerly GSH-depleted, growth-arrested cultures resumed cell cycle progression. The results suggest that the cellular response to specific mitogens is interrelated with the cellular thiol redox status. Cells that possess a thiol redox status below a threshold response point may have compromised Ca2+ sequestration and/or mobilization and therefore may be incapable of initiating the mitogen induced response cascade that culminates in cell cycle progression.
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PMID:Association of cellular thiol redox status with mitogen-induced calcium mobilization and cell cycle progression in human fibroblasts. 190 Aug 43

We have used 1,3-bis(2-chloroethyl)-1-nitrosourea, a selective inhibitor of oxidized glutathione reductase (GSSG-R), to examine the role of this enzyme in regulating the hexose monophosphate shunt (HMS) and to explore how a variety of agents influence glucose decarboxylation in intact human red blood cells (RBCs). Substances tested included primaquine and several other drugs that are specially hemolytic and methemoglobinemic in glucose-6-phosphate dehydrogenase (G6PD) deficiency and related disorders. The results allowed us to distinguish and quantitate contrasting modes of HMS stimulation and to clarify how RBCs respond to different classes of oxidants. Some agents like methylene blue (MB), phenazine methosulfate, and pyrroline carboxylate do not require GSSG-R to increase CO2 production; they activate G6PD and 6-phosphogluconic dehydrogenase by directly oxidizing reduced nicotinamide adenine dinucleotide phosphate (NADPH) to oxidized nicotinamide adenine dinucleotide phosphate (NADP). Other compounds, like ascorbate, nitrofurantoin, and doxorubicin, oxidize GSH primarily; CO2 increases indirectly only when GSSG-R, activated by glutathione disulfide (GSSG), raises the level of NADP. Chemicals like primaquine, daunorubicin, and methylphenylazoformate trigger the HMS by independently oxidizing both NADPH and GSH. Unlike MB, most drugs that are hemolytic in G6PD deficiency activate the HMS in a manner that depends to a variable extent on GSSG-R. This variability may explain hitherto puzzling clinical and pharmacogenetic differences between primaquine and diaminodiphenylsulfone-induced hemolysis.
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PMID:Defenses against oxidation in human erythrocytes: role of glutathione reductase in the activation of glucose decarboxylation by hemolytic drugs. 190 43

1. The redox properties of the active-site dithiol/disulphide groups of PDI were determined by equilibrating the enzyme with an excess of GSH + GSSG, rapidly alkylating the dithiol form of the enzyme to inactivate it irreversibly, and determining the proportion of the disulphide form by measuring the residual activity under standard conditions. 2. The extent of reduction varied with the applied redox potential; to a first approximation, the data fitted a model in which all the enzyme dithiol/disulphide groups are independent and equivalent and the equilibrium constant between these sites and the GSH/GSSG redox couple is 42 microM at pH 7.5. 3. The standard redox potential for PDI active-site dithiol/disulphide couples was calculated from this result and found to be -0.11 V; hence PDI is a stronger oxidant and weaker reductant than GSH, nicotinamide cofactors, thioredoxin and dithiothreitol. 4. The redox equilibrium data for PDI with the GSH/GSSG redox couple showed sigmoidal deviations from linearity. The sigmoidicity could be modelled closely by assuming a Hill coefficient of 1.5. 5. This evidence of co-operative interactions between the four active sites in a PDI dimer was extended by studying the reaction between PDI and homobifunctional alkylating agents with various lengths between the reactive groups. A species whose electrophoretic mobility suggested it contained an intrachain cross-link was observed in all cases, whereas there was no evidence for cross-linking between the chains of the PDI homodimer. Most effective cross-linking was achieved with reagents containing five or more methylene spacer groups, implying a minimum distance of 1.6 nm (16 A) between the active-site reactive groups within the two thioredoxin-like domains of the PDI polypeptide.
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PMID:Redox properties and cross-linking of the dithiol/disulphide active sites of mammalian protein disulphide-isomerase. 202 21

In the present study, the effect of thiol redox and its possible role in the inhibitory effect of nicotinamide on renal brush-border membrane (BBM) phosphate uptake was examined. Addition of thiol reducing agent, dithiothreitol (DTT, 5 mM), caused an increase, while addition of thiol oxidant, diamide (DM, 5 mM) caused a reversible decrease in sodium-dependent BBM phosphate uptake. Kinetic analyses revealed an increase in both Vmax and Km by DTT, and a decrease in Vmax by DM. These results suggest that thiol redox influences BBM phosphate uptake with sulfhydryl (SH) groups relate to its capacity and disulfide (SS) groups to its affinity for phosphate. Since changes in cytosolic NAD levels may affect BBM thiol redox through changes in redox states of NADP and glutathione systems, we have examined such possibility by studying the effect of nicotinamide (NM). Incubation of proximal tubules with NM (10 mM) induced an oxidative effect on redox states of cytosolic NAD, NADP systems as inferred from decreased cellular lactate/pyruvate, malate/pyruvate, respectively. Measurements of cytosolic glutathiones and BBM thiols also revealed that NM pretreatment shifted the cytosolic glutathione redox (GSH/GSSG) and BBM thiol redox (SH/SS) toward more oxidized state. On the other hand, incubation of proximal tubules with NM suppressed phosphate uptake by the subsequently isolated BBM vesicles. The lower phosphate uptake by NM-pretreated BBM vesicles was reversed by DTT and was resistant to the inhibitory effect of DM. These results thus suggest that BBM thiol oxidation may be involved in the inhibitory effect of NM on BBM phosphate uptake.
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PMID:Thiol redox and phosphate transport in renal brush-border membrane. Effect of nicotinamide. 213 97


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