Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1260386 (GSH)
 38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic ethanol feeding to rats increases the sinusoidal component of hepatic glutathione (GSH) efflux, despite a lower steady-state GSH pool size. In the present studies, no increase of biliary GSH efflux in vivo was found in chronic ethanol-fed cells. Studies were performed on ethanol-fed and pair-fed cells to identify the kinetic parameters of cellular GSH concentration-dependent efflux. The relationship between cytosolic GSH and the rate of efflux was modeled by the Hill equation, revealing a similar Vmax, 0.22 +/- 0.013 vs. 0.20 +/- 0.014 nmol/min per 10(6) cells for ethanol-fed and pair-fed cells, respectively, whereas the Km was significantly decreased (25.3 +/- 2.3 vs. 33.5 +/- 1.4 nmol/10(6) cells) in ethanol-fed cells. The difference in Km was larger when the data were corrected for the increased water content in ethanol-fed cells. We found a direct correlation between mitochondria and cytosolic GSH, revealing that mitochondria from ethanol-fed cells have less GSH at all cytosolic GSH values. The rate of resynthesis in depleted ethanol-fed cells in the presence of methionine and serine was similar to control cells and gamma-glutamylcysteine synthetase remained unaffected by chronic ethanol. However, the reaccumulation of mitochondrial GSH as the cytosolic pool increased was impaired in the ethanol cells. The earliest time change in GSH regulation was a 50% decrease in the mitochondrial GSH at 2 wk.
 ...
PMID:Effects of chronic ethanol feeding on rat hepatocytic glutathione. Relationship of cytosolic glutathione to efflux and mitochondrial sequestration. 270 32

Sertoli cells play a major role in the regulation of spermatogenic cell energy metabolism and differentiation. This study demonstrates that Sertoli cells are essential for the maintenance of spermatogenic cell glutathione (GSH), an important intracellular reductant and detoxicant. Primary spermatocytes and round spermatids isolated from Xenopus laevis contained 1.5 +/- 0.1 mM GSH, but sperm lacked detectable GSH. During a 5-day culture period, isolated spermatocytes and spermatids lost 80% of the initial GSH (t 1/2 = 55 h). The levels of GSH were unaffected by L-buthionine-SR-sulfoximine (BSO), a selective inhibitor of GSH synthesis. Cultures of testicular lobules and spermatocysts (composed of germ cells and Sertoli cells) depleted of interstitial tissue lost only 30% of their initial GSH in 4.5 days; the GSH levels decreased during treatment with BSO. Spermatogenic cells in cultured testes maintained their GSH levels for 7 days by a BSO-sensitive mechanism. These results demonstrate that the intracellular GSH levels of spermatogenic cells are dependent upon germ cell-somatic cell interactions. Spermatogenic cells were shown to possess gamma-glutamyl transpeptidase, glutathione synthetase, 5-oxoprolinase, and gamma-glutamylcysteine synthetase activities. [35S] Cysteine incorporation and distribution as analyzed by high performance liquid chromatography (HPLC) showed that isolated spermatogenic cells are capable of GSH synthesis. The rate of GSH synthesis, however, was insufficient to compensate for GSH turnover. These results demonstrate that production of spermatogenic cell GSH is dependent upon Sertoli cells. To our knowledge, this is the first evidence that interactions between different cell types may be of significance in GSH metabolism.
 ...
PMID:Spermatogenic cell-somatic cell interactions are required for maintenance of spermatogenic cell glutathione. 272 29

We examined the role of intracellular glutathione (GSH) in the defense of endothelial cells against oxidized low density lipoprotein (OX-LDL). Incubation of cultured bovine endothelial cells with OX-LDL produced a loss of intracellular GSH, followed by lysis. A decrease in the cellular stores of GSH by treating the endothelial cells with buthionine sulfoximine, an irreversible inhibitor of gamma-glutamylcysteine synthetase, increased the susceptibility of endothelial cells to lysis by OX-LDL. In contrast, an increase in cellular GSH level by treatment with L-2-oxothiazolidine-4-caboxylate, an effective intracellular cysteine delivery agent, reduced the toxicity of OX-LDL. These findings suggest that intracellular GSH plays an important role in the defense of endothelial cells against OX-LDL, and that the mechanism of OX-LDL toxicity is related to the depletion of intracellular GSH.
 ...
PMID:Protective role of intracellular glutathione against oxidized low density lipoprotein in cultured endothelial cells. 278 44

Sprague-Dawley rats (200-260 g) were anesthetized with chloral hydrate (400 mg/kg) and polyethylene cannulae were permanently implanted into the lateral ventricles. One or two days later, L-buthionine-[S,R]-sulfoximine (L-BSO), an apparently selective inhibitor of gamma-glutamylcysteine synthetase, was administered intracerebroventricularly through the cannulae. The brain content of glutathione (GSH) was determined by HPLC with electrochemical detection (gold/mercury electrode) using N-acetylcysteine as internal standard. A time-course study of the changes in the striatum following a single dose of L-BSO (3.2 mg) revealed a maximal depletion of GSH (-60%) approximately 48 h after the administration. The effects of various doses of L-BSO on GSH in the striatum, in the limbic region, and in the cortex were assessed at 24 h and 48 h after the administration. L-BSO (0.02-3.2 mg) produced dose-dependent reductions of GSH in all brain regions studied at both time intervals. In a long-term experiment L-BSO (3.2 mg) was administered every second day. After 4 days, i.e., after two injections, striatal GSH was reduced by approximately 70%. No further depletion of GSH was obtained by additional injections of L-BSO, but GSH was maintained at this low level for the 12 days studied. These results suggest that L-BSO, administered intracerebroventricularly, would serve as a useful tool for evaluation of the biological role of GSH in the CNS.
 ...
PMID:Intracerebroventricular administration of L-buthionine sulfoximine: a method for depleting brain glutathione. 280 98

The levels of GSH-related enzyme activities during pregnancy were determined. A significant increase in Selenium-dependent GSH peroxidase and GSH S-transferase E activity was observed. A concomitant increase in gamma-glutamylcysteine synthetase was measured, which indicated an increased ability to synthesize the tripeptide.
 ...
PMID:Glutathione-related enzyme activities in pregnant rat liver. 285 28

The constituent amino acids of reduced glutathione (GSH), GSH itself, and D-alpha-tocopherol inhibited 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC, L-ornithine carboxy-lyase, EC 4.1.1.17) activity in mouse epidermis in vivo and in vitro. The inhibitory effects of cysteine (Cys), GSH and D-alpha-tocopherol on ODC induction were proportional to their abilities to decrease the incidence of skin tumors in the initiation-promotion protocol. Moreover, the ability of the constituent amino acids of GSH and GSH to inhibit TPA-induced ODC activity correlated well with their ability to increase the ratio of GSH/oxidized glutathione (GSSG) in isolated epidermal cells. In vitro, various treatments with 1 mM GSH, 1 mM glutamic acid (Glu), 1 mM glycine (Gly), 0.4 mM Cys and/or 0.2 mM cystine (CysCys) inhibited dramatically the sharp decline in the intracellular ratio of GSH/GSSG caused by 0.1 microM TPA. Since the inhibitory effects of Cys on both the decrease in the ratio of GSH/GSSG and the induction of ODC activity by TPA were greatly reduced by the inhibitors of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase, it is suggested that some of the inhibitory effects of Glu, Cys and Gly on tumor promotion could result from their interference with the metabolism of the tripeptide GSH, a natural antioxidant which inhibits chemical carcinogenesis. The free radical scavenger D-alpha-tocopherol, which did not alter directly the intracellular ratio of GSH/GSSG, also prevented completely the decrease in the ratio of GSH/GSSG caused by TPA. These results, therefore, suggest that GSH level-raising agents and other antioxidants might inhibit by diverse means the effects of TPA on GSH metabolism and skin tumor promotion.
 ...
PMID:Inhibitory effects of glutathione level-raising agents and D-alpha-tocopherol on ornithine decarboxylase induction and mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. 285 27

Normal sheep erythrocytes as well as glutathione- (GSH-) deficient and arginase-deficient sheep erythrocytes have been characterized by 1H nuclear magnetic resonance spectroscopy. The GSH deficiency is a result of defective amino acid transport (lesion 1), diminished gamma-glutamylcysteine synthetase activity (lesion 2), or both (lesions (1 + 2)). 1H-NMR spectra of normal sheep erythrocytes are similar to those for human erythrocytes, and consist of resonances from a number of small intracellular molecules, including GSH. In contrast, the resonances for GSH in the GSH-deficient erythrocytes are much weaker, and strong resonances are observed for lysine, threonine and ornithine or arginine, depending on the arginase activity, in erythrocytes with lesion 1 and lesions (1 + 2). A comparison of the intensity of GSH resonances in spectra for normal and GSH-deficient erythrocytes with GSH levels determined spectrophotometrically following reaction with the nonspecific thiol reagent 5,5'-dithiobis(2-nitrobenzoate) (DTNB) indicates that either not all of the GSH determined with Ellman's reagent is free and observable by 1H-NMR or that not all of the thiol determined by Ellman's reagent is GSH. If the latter is the case, the GSH levels determined with Ellman's reagent for erythrocytes with lesions (1 + 2) are most affected, which might account for their high susceptibility to oxidative stress.
 ...
PMID:Characterization of normal, glutathione-deficient and arginase-deficient sheep erythrocytes by 1H-NMR spectroscopy. 286 19

The nucleotide sequence of the gsh I gene for gamma-glutamylcysteine synthetase(GSH I) of Escherichia coli B has been determined. The gsh I structural gene contains 1557 bases in length and predicted a ploypeptide of 518 amino acids with a calculated molecular weight of 58,251. The value is in good agreement with that obtained from gel filtration and SDS/PAGE of GSH I. The initiation codon 5 bp downstream of putative Shine-Dalgarno sequence was an unusual TTG, which encoded methionine. For transcription, two sets of consensus promoter signals(-10 and -35 regions) overlapping each other were identified. The terminator signal shows the favored stem-loop structure with an adequate free energy delta G = -22.80 kcal/mol.
 ...
PMID:The nucleotide sequence of the gene for gamma-glutamylcysteine synthetase of Escherichia coli. 287 55

Experiments were conducted to determine if the circadian variations previously observed in hepatic reduced glutathione (GSH) concentrations also occurred in the associated enzymatic activities involved in the synthesis (gamma-glutamylcysteine synthetase) and degradation (gamma-glutamyl transferase) of glutathione using male CF-1 mice. All parameters were measured at four hour intervals over a 24-h period under normal (L: 0600-1800 h) and reversed (L: 1800-0600 h) lighting schedules. Circadian rhythms were found in each parameter under both lighting schedules. With GSH content, the rhythms' peak occurred at 0200 h and the nadir at 1400 h under the normal lighting schedule and was reversed (peak: 1800 h; nadir; 0600 h) under reversed lighting. The enzymatic activities also varied in a circadian manner with a phase shift in the peak and nadir occurring with a change in lighting schedule. Liver weight varied in a circadian manner under both lighting schedules with greatest weights occurring at the end of the dark phase. These data show that not only does GSH content vary in a circadian manner but that associated enzyme activities do as well. However, the hepatic enzyme activities did not correlate well with the GSH rhythm and, thus, do not provide a mechanistic rationale for the GSH rhythm.
 ...
PMID:Circadian variations in hepatic glutathione content, gamma-glutamylcysteine synthetase and gamma-glutamyl transferase activities in mice. 288 81

The oxidized form of glutathione transport was studied in human erythrocytes in pyrimidine 5'-nucleotidase (P5N) deficiency, a disorder in which the amounts of CTP and UTP in the erythrocytes are elevated. The inhibition of ATP-requiring oxidized glutathione (GSSG) transport by CTP and UTP is believed to play a role in elevating the levels of the reduced form of glutathione (GSH) in the erythrocytes of patients with P5N deficiency. The current investigation was undertaken to determine if GSSG transport actually decreases in the erythrocytes of such patients. Erythrocytes from a 17-year-old patient and a 13-year-old patient with P5N deficiency hemolytic anemia and from ten normal subjects were used as materials for the experiment. Erythrocytes, which had been previously incubated with [3H]glycine, were incubated at 37 degrees C, and the rate of [3H]GSSG transported by the cells was estimated. The velocity of GSSG transport out of the erythrocytes was quite low in the patients, 3.17-3.65 nmol GSSG/ml erythrocytes/hr at 37 degrees C in one case, and 3.30 nmol GSSG/ml erythrocytes/hr in the other case, vs that in the normal controls (6.00 +/- 0.80 nmol GSSG/ml erythrocytes/hr; mean +/- SD). The activity of gamma-glutamylcysteine synthetase and glutathione synthetase did not decrease in the patients. Decreased transport activity of GSSG in addition to a normal synthesis rate for GSH may explain the increased concentration of erythrocyte GSH in P5N deficiency.
 ...
PMID:Erythrocyte-oxidized glutathione transport in pyrimidine 5'-nucleotidase deficiency. 288 6


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>