UMLS:C1260386 - FACTA Search

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

The GSH concentration of rabbit erythrocytes was monitored under conditions of large net transport of alanine, phenylalane and lysine in the absence of glucose. In no case was there an appreciable alteration in GSH concentration during amino acid uptake. It is suggested that the gamma-glutamyltransferase-gamma-glutamylcyclotransferase pathway does not participate in amino acid transport by these cells.
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PMID:Evidence against the participation of the gamma-glutamyltransferase-gamma-glutamylcylclotransferase pathway in amino acid transport by rabbit erythrocytes. 0

After secretion into bile, glutathione (GSH) and GSH-conjugates are catabolized by gamma-glutamyltransferase (gamma-GT) and dipeptidases yielding glutamate, cysteine, glycine and cysteine S-conjugates, and these products are then partially reabsorbed from the biliary tree. Because methyl mercury is thought to be secreted into bile as a GSH- complex, it may be subject to a similar intrahepatic cycle, thus delaying its elimination. To examine this possibility guinea pigs were dosed with 203Hg-methyl mercury (10 mumol/kg i.v.), followed by a retrograde intrabiliary infusion of Krebs-Henseleit buffer (control) or acivicin (an inhibitor of gamma-GT). Acivicin increased biliary excretion of 203Hg by 41%, and GSH from 0.14 +/- 0.10 to 2.02 +/- 0.26 nmol/min.g of liver. Bile analyzed by gel filtration chromatography revealed that CH(3)203Hg-GSH accounted for most of this increased 203Hg excretion. When CH(3)203Hg-complexes of GSH, cysteine and albumin were introduced directly into the biliary tree by retrograde infusion, 203Hg recovery in bile was significantly lower than recovery of the nonabsorbable marker [14C]sucrose, ranging from 26.0 +/- 2.9% for CH(3)203Hg-cysteine to 48.7 +/- 5.1% for CH(3)203Hg-albumin and approximately 60% for [14C]sucrose. Acivicin pretreatment significantly increased 203Hg excretion into bile after retrograde infusion of CH(3)203Hg-GSH, whereas 203Hg recovery after retrograde infusion of CH(3)203Hg-cysteine remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:gamma-Glutamyltransferase-dependent biliary-hepatic recycling of methyl mercury in the guinea pig. 135 55

Biliary excretion of glutathione disulfide (GSSG) is used as an index of oxidative stress. Analysis of endogenous thiols and disulfides in rat bile by reverse phase high performance liquid chromatography with electrochemical detection revealed an unknown disulfide which eluted immediately after GSSG. This disulfide was tentatively identified as the mixed disulfide of glutathione (GSH) and cysteinylglycine (Cys-Gly), based on its coelution on a reverse phase column with the synthetic GS-Cys-Gly. GS-Cys-Gly was also detected in bile of other species. On analyzing species differences in biliary excretion of GSH-related thiols and disulfides, it was concluded that biliary excretion of GS-Cys-Gly was related to the excretion of both GSSG and Cys-Gly, which is formed from GSH by gamma-glutamyltransferase (gamma-GT)-catalyzed hydrolysis. Species with low hepatic gamma-GT (i.e., hamsters and mice) excreted little Cys-Gly in bile. These animals excreted negligible amounts of GS-Cys-Gly even when biliary excretion of GSSG was markedly increased by paraquat-induced oxidative stress. Rats and guinea pigs, which have high hepatic gamma-GT activities, excreted large amounts of both Cys-Gly and GS-Cys-Gly. Treatment of rats with acivicin, an inhibitor of gamma-GT, decreased the biliary excretion of both Cys-Gly and GS-Cys-Gly. Paraquat treatment of rats resulted in an increase in GSSG excretion with concomitant increase of GS-Cys-Gly excretion. Rabbits, which also have high hepatic gamma-GT activity, excreted little GS-Cys-Gly into bile.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of the mixed disulfide of glutathione and cysteinylglycine in bile: dependence on gamma-glutamyl transferase and responsiveness to oxidative stress. 135 52

The hepatocarcinogenic responses of rats to aflatoxin B1 (AFB1) are believed to depend on microsomal activation of the toxin, followed by macromolecular binding. Dietary protein insufficiency is reported to reduce the level of microsomal metabolism, and therefore would be expected to reduce the AFB1-induced carcinogenicity. Indeed, diminished hepatocarcinogenicity in low-protein diet fed weanling rats that had received AFB1 has been reported. In the present study, carcinogenicity and other toxic effects of AFB1 (0.5 p.p.m.) fed to weanling male Fischer F344 rats on a low-protein diet (5%) or normal-protein (20%) diet for up to 8 weeks were examined. In our study, in contrast with the previous report, all animals that had survived some initial toxicity were found to have developed hepatic tumors or hyperplastic gamma-glutamyltransferase-positive foci a year later. The low-protein diet also produced sub-acute toxicity after AFB1 exposure in the weanling rats, leading to severe histological changes, and the death of about half the animals after 3-4 weeks of exposure. Animals fed an AFB1-containing normal-protein diet also exhibited AFB1-induced hepatocarcinogenicity, but not the sub-acute toxicity. The levels of hepatic enzymes involved in AFB1 metabolism were examined in animals fed the low- or normal-protein diets in the absence of AFB1. The low-protein diet, fed to 3 week weanlings for the subsequent 5 weeks, decreased hepatic cytochrome P450 levels, as well as the in vitro capacity of microsomal fractions to form AFB1-8,9-dihydrodiol, an index of AFB1-8,9-epoxide formation. Rats on a normal-protein diet did not show these changes. This discrepancy between the observed increase in sub-acute toxicity and decrease in microsomal activities in the low-protein fed animals implies that the toxic effects observed in these rats were not directly related to metabolic activation of the toxin. In contrast to the diminished microsomal in vitro AFB1 activation, however, in vivo AFB1-DNA adduct formation ability in rats receiving the low-protein diet in the absence of AFB1 was found to become elevated more rapidly during the 5 week experimental feeding period, compared with animals receiving the normal-protein diet. This was accompanied by a more rapid fall in the levels of AFB1-glutathione S-transferase isozyme activity in the low-protein fed animals. The results of this study on weanling rats support the importance of AFB1-GSH in protecting against the carcinogenic responses to AFB1, and probably also the sub-acute toxicity of the latter.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of dietary protein level on aflatoxin B1 actions in the liver of weanling rats. 142 44

alpha-Naphthylisothiocyanate (ANIT) injures bile duct epithelium and hepatic parenchymal cells in rats. It is commonly believed that ANIT must undergo bioactivation by hepatic, cytochrome P450-dependent mixed-function oxidases (MFO), since agents which are inducers or inhibitors of hepatic MFO activity enhance or attenuate, respectively, the liver injury associated with ANIT. Several of these agents also affect hepatic glutathione (GSH) content and/or GSH S-transferase activity in a manner to suggest a causal role for GSH in ANIT-induced hepatotoxicity. To determine whether GSH might be involved in the mechanism of injury, buthionine sulfoximine (BSO), diethyl maleate (DEM), or phorone was used to reduce hepatic non-protein sulfhydryl (NPSH) content, an indicator of GSH content. Twenty-four hours after ANIT treatment, rats exhibited cholestasis and elevations in serum of total bilirubin concentration, total bile acid concentration, aspartate aminotransferase (AST) activity, and gamma-glutamyltransferase activity. Cotreatment of rats with BSO decreased NPSH content by 70% at 24 hr and prevented the cholestasis and elevations in serum markers of liver injury caused by ANIT. Likewise, cotreatment of rats with DEM afforded protection against markers of liver injury. Phorone treatment attenuated ANIT-induced elevations in serum total bilirubin concentration and AST activity. Although BSO treatment afforded protection against ANIT-induced liver injury at 24 hr, the injury was evident at 48 hr, and it appeared to coincide with a return of hepatic NPSH content. These results suggest that GSH plays a causal or permissive role in the liver injury caused by ANIT.
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PMID:Protection against alpha-naphthylisothiocyanate-induced liver injury by decreased hepatic non-protein sulfhydryl content. 167 29

Acute administration of alpha-naphthylisothiocyanate (ANIT) to rats has been used as a model of intrahepatic cholestasis. The mechanism of toxicity of ANIT is unknown, although recent evidence suggests a causal or permissive role for glutathione (GSH) (Dahm LJ and Roth RA, Biochem Pharmacol 42: 1181-1188, 1991). In these studies, ANIT treatment elevated hepatic non-protein sulfhydryl (NPSH) content, an indicator of GSH content, when liver injury was evident. The purpose of the present study was to characterize the effects of ANIT on hepatic NPSH content and to relate these changes to the development of liver injury. In rats fasted for 24 hr, administration of ANIT (100 mg/kg, per os [p.o.]) did not change hepatic NPSH content, bile flow, or serum measurements of total bilirubin concentration, alanine aminotransferase (ALT) activity, or gamma-glutamyltransferase (GGT) activity by 12 hr post-treatment relative to corn oil vehicle controls. However, by 24 hr after ANIT treatment, rats exhibited cholestasis and elevations in serum markers of liver injury. These markers were associated temporally with an increase in hepatic NPSH content, which consisted entirely of GSH. To determine whether the cholestasis caused by ANIT treatment might have caused the elevation of hepatic NPSH content, an extrahepatic cholestasis in rats was produced by ligation of the common bile duct. Bile duct ligation elevated hepatic NPSH content between 6 and 12 hr after ligation. Administration to rats of a non-hepatotoxic analog of ANIT, beta-naphthylisothiocyanate, also elevated hepatic NPSH content 24 hr after treatment. Taken together, these results indicate that the elevation in hepatic NPSH content after ANIT treatment is associated temporally with the onset of liver injury, but this elevation does not appear to participate causally in the mechanism of injury.
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PMID:Relationship between alpha-naphthylisothiocyanate-induced liver injury and elevations in hepatic non-protein sulfhydryl content. 167 30

The relationship of the rate of extraction of circulating glutathione (GSH) to the level of activity of gamma-glutamyltransferase (GGT) of hepatocytes of nodular and of cancer-bearing livers was studied in rats perfused in situ via the portal vein. Fischer adult male rats with many nodules (10 rats) or few (nine rats) liver nodules and four rats with hepatomas were compared as to their ability to remove GSH (10 microM) from the perfusate. The rate of extraction of infused GSH was directly proportional to the numbers of GGT(+)-hepatocytes in the liver tissue, inhibitable completely by adding the GGT inhibitor serine borate at 6-8 mM in the perfusate, and significantly enhanced in all rats by adding the gamma-glutamyl acceptor glycyl-glycine to the perfusate. These results suggest that nodules and cancers are able to remove GSH much more efficiently from the circulation than the surrounding liver tissue and that their enhanced GSH utilization is directly dependent on their GGT activity, which is present at much higher levels than in the surrounding tissues. The increases in GGT activity in nodule hepatocytes and enhanced ability to utilize GSH could be critical factors in the response to resistance selection of chemical hepatocarcinogenesis.
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PMID:Utilization of circulating glutathione by nodular and cancerous intact rat liver. 168 39

The role of gamma-glutamyltransferase (gamma-GT) in renal ammoniagenesis, glutamine (Gln), and glutathione (GSH) utilization was evaluated in the intact functioning rat kidney of subtotal nephrectomy (SNX) model of chronic renal failure (CRF). NH4+ derived from extracellular gamma-GT hydrolysis of Gln and GSH was differentiated from the intramitochondrial phosphate-dependent glutaminase by using acivicin, a gamma-GT-specific inhibitor. In the control (C) group Gln extraction accounted for 61% of total NH4+ production (sum of renal venous and urinary NH4+), but only 41% in SNX group. In the SNX group GSH extraction accounted for 10% of total NH4+ production, but only 1% in the C group. Acivicin inhibited 44% and 33% of total NH4+ production in SNX and C group respectively, as compared to baseline before acivicin. In CRF, gamma-GT a key enzyme of the gamma-glutamyl cycle plays a significant role in adaptive ammoniagenesis.
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PMID:Adaptive ammoniagenesis in chronic renal failure. 169 86

The glutathione (GSH) content of rat kidney decreases after cessation of blood flow, falling to 40% of control levels 35 min after renal artery occlusion [R. C. Scaduto, Jr., V. H. Gattone II, L. W. Grotyohann, J. Wertz, and L. F. Martin. Am. J. Physiol. 255 (Renal Fluid Electrolyte Physiol. 24): F911-F921, 1988]. Renal GSH levels remained depressed for at least 2 h after resumption of blood flow. Because GSH functions in the removal of free radicals, and lipid peroxidation is a free radical-initiated process that occurs in the ischemic kidney, we investigated the fate of this GSH pool in the ischemic kidney. Using high-performance liquid chromatography to measure thiols, we found the loss of GSH to be associated with a stoichiometric accumulation of cysteine in the kidney. Moreover, preischemic labeling of the renal GSH pool with 35S led to accumulation of [35S]cysteine during ischemia that had the same specific activity as that of tissue GSH. Formation of cysteine during ischemia was suppressed in rats pretreated with acivicin, an inhibitor of gamma-glutamyltransferase (gamma-GT), although the degree of suppression was small in comparison to the extent of gamma-GT inhibition. During the initial 2 min of blood reflow after ischemia, tissue cysteine returned to control levels, and a transient increase in the cysteine content of renal venous blood was observed. After ischemia, renal GSH levels remained depressed, but postischemic GSH levels could be increased by administration of N-acetylcysteine during the ischemic period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutathione catabolism by the ischemic rat kidney. 197 65

Although the liver is recognized as a major site of glutathione (GSH) synthesis, it is thought to play only a minor role in GSH catabolism. This is primarily because in the rat, the most commonly used experimental animal, hepatic gamma-glutamyltransferase (gamma-GT) activity is very low, whereas kidney activity is quite high. gamma-GT is the only enzyme known to catalyze the initial step in GSH degradation. The present work compares gamma-GT and dipeptidase activities in liver, kidney, and gallbladder of six mammalian species to assess the importance of hepatobiliary catabolism of GSH, relative to renal degradation. Marked species differences were observed in gamma-GT activities, and in kidney to liver (K/L) ratios for both gamma-GT concentration (milliunits/mg protein) and whole organ activities (total activity per liver or two kidneys). The K/L concentration ratios for gamma-GT activities ranged from 875 in the rat to 15 in the guinea pig. Whole organ gamma-GT ratios were approximately 150 in mouse and rat, and only 2-5 in guinea pig. pig, and macaque. Human K/L ratios calculated from gamma-GT activities reported previously were similar to those of the guinea pig. Species differences were also observed in K/L ratios for dipeptidase activities, though these differences were not as large as those for gamma-GT, gamma-GT and dipeptidase activities were also measured in gallbladders of all species examined (except rat which does not have this organ), and were found to be comparable to those of liver. These results suggest that in species such as the guinea pig and perhaps humans, the liver and biliary tree play a prominent role in GSH turnover. Because of the low hepatic and high renal gamma-GT activities of the rat, and because it does not have a gallbladder, this species may not be the best model for studying the catabolism of GSH and GSH conjugates. Use of the rat model may underestimate the contribution of liver, and overestimate that of kidney, in these degradative processes.
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PMID:Glutathione-degrading capacities of liver and kidney in different species. 197 72

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