Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that exogenous lactate impairs mechanical function of reperfused ischaemic hearts, while pyruvate improves post-ischaemic recovery. The aim of this study was to investigate whether the diverging influence of exogenous lactate and pyruvate on functional recovery can be explained by an effect of the exogenous substrates on endogenous protecting mechanisms against oxygen-derived free radicals. Isolated working rat hearts were perfused by a Krebs-Henseleit bicarbonate buffer containing glucose (5 mM) as basal substrate and either lactate (5 mM) or pyruvate (5 mM) as cosubstrate. In hearts perfused with glucose as sole substrate the activity of glutathione reductase was decreased by 32% during 30 min of ischaemia (p < 0.10 versus control value), while the activity of superoxide dismutase and catalase was reduced by 27 and 35%, respectively, during 5 min of reperfusion (p < 0.10 versus control value). The GSH level in the glucose group was reduced by 29% following 30 min of ischaemia and 35 min of reperfusion (p < 0.10). In lactate- and pyruvateperfused hearts there were no significant decreases of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activity during 30 min of ischaemia, 5 min of reperfusion or 35 min of reperfusion. In pyruvate-perfused hearts the glutathione peroxidase activity was even increased by 43% during 30 min of ischaemia (p < 0.05). Glutathione levels (reduced and oxidized) did not markedly change in the lactate and pyruvate groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1995 May 24
PMID:The influence of lactate, pyruvate and glucose as exogenous substrates on free radical defense mechanisms in isolated rat hearts during ischaemia and reperfusion. 756 44

1. MC has been shown to inhibit the uptake of L-glutamate and increase D-aspartate release from preloaded astrocytes in a dose-dependent fashion. 2. Two sulfhydryl (SH-)-protecting agents; reduced glutathione (GSH), a cell membrane-nonpenetrating compound, and the membrane permeable dithiothreitol (DTT), have been shown consistently to reverse the above effects. MC-induced D-aspartate release is completely inhibited by the addition of 1 mM DTT or GSH during the actual 5-min perfusion period with MC (5 microM); when added after MC treatment, DTT fully inhibits the MC-induced D-aspartate release, while GSH does not. 3. Neither DTT nor GSH, in the absence of MC, have any effect on the rate of astrocytic D-aspartate release. Other studies demonstrate that although MC treatment (5 microM) does not induce astrocytic swelling, its addition to astrocytes swollen by exposure to hypotonic medium leads to their failure to volume regulate. 4. Omission of calcium from the medium greatly potentiates the effect of MC on astrocytic D-aspartate release, an effect which can be reversed by cotreatment of astrocytes with the dihydropyridine Ca(2+)-channel antagonist nimodipine (10 microM), indicating that one possible route of MC entry into the cells is through voltage-gated L-type channels.
Cell Mol Neurobiol 1994 Dec
PMID:Astrocytes as potential modulators of mercuric chloride neurotoxicity. 764 Dec 25

The degradation rate of H2O2, added to the incubation medium, and glutathione (GSH) peroxidase activity were measured in cultures of FRTL-5 cells and porcine thyroid cells. The H2O2 degradation rate increased proportionally to the H2O2 concentration and was in FRTL-5 cells, cultured with TSH, approximately 50 nmol/min and mg DNA at 0.01 mM H2O2 and approximately 3 x 10(4) nmol/min and mg DNA at 10 mM H2O2. The GSH peroxidase activity in the same cells was equivalent to an H2O2 degradation of approximately 400 nmol/min and mg DNA. The involvement of enzymes in H2O2 degradation was studied by inhibiting catalase with aminotriazole (ATZ) and reducing GSH peroxidase by omitting glucose in the incubation medium. At 0.1 mM H2O2, ATZ or glucose omission alone did not measurably reduce H2O2 degradation but did so when combined. At 10 mM H2O2 ATZ caused a clear inhibition whereas glucose omission had no additive effect. These observations indicate that GSH peroxidase was involved in H2O2 degradation only at low H2O2 concentrations. The GSH peroxidase activity decreased by reduction of the selenite supply and increased after replenishment. The recovery of the enzyme activity required the presence of TSH in FRTL-5 cells but not in porcine thyrocytes.
Mol Cell Endocrinol 1995 Apr 28
PMID:Hydrogen peroxide degradation and glutathione peroxidase activity in cultures of thyroid cells. 764 59

We previously reported that the activity of gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH synthesis, is under both hormonal and cell density regulation in cultured rat hepatocytes. Specifically, the addition of insulin or hydrocortisone to culture media or the lowering of the initial plating cell density increased cell GSH by increasing the activity of GCS. In the present study, we examined the molecular mechanism of these effects. To determine whether the increase in GCS activity is associated with an increase in GCS heavy subunit (GCS-HS) mRNA expression, the steady state mRNA levels of GCS-HS were examined with the use of Northern blots. After 24-hr treatment of high density (0.6 x 10(5) cells/cm2) cultured rat hepatocytes with insulin (1 micrograms/ml) or hydrocortisone (50 nM), the steady state GCS-HS mRNA level increased by approximately 1-2 fold. When the plating density was decreased to 0.1 x 10(5) cells/cm2, the steady state GCS-HS mRNA level also increased by 1-2 fold 24 hr later. An increase in the steady state GCS-HS mRNA level was found within 4 hr of either hormonal treatment or cell density manipulation. The increase in steady state GCS-HS mRNA level resulted from increased gene transcription, as the transcriptional rates of GCS-HS after hormonal or cell density manipulation were increased by 2-3-fold, whereas the rates of GCS-HS mRNA degradation remained unchanged. Western blotting confirmed the increase in GCS-HS protein level after hormone treatment or lowering of plating cell density. When examined in vivo, the steady state GCS-HS mRNA level decreased by 50% in a rat in which diabetes had been induced with streptozotocin for 1 week; this was prevented with insulin replacement. In summary, GCS-HS gene expression is under both hormonal and cell density regulation.
Mol Pharmacol 1995 Aug
PMID:Hormonal and cell density regulation of hepatic gamma-glutamylcysteine synthetase gene expression. 765 54

Glutathione (GSH) depletion in mitogen-stimulated T lymphocytes has been shown to markedly inhibit their proliferative response. This block in proliferation is associated with a significant reduction in total RNA and DNA synthesis; however, the specific mechanism involved in this inhibition of proliferation is unknown. Miller et al. have reported that lowering intracellular GSH levels by greater than 30%, in murine and human tumor cell lines of non-hematopoietic origin, leads to down-regulation of HA-, Ki- and N-ras oncogene expression [Miller. A.C., Gafner, J., Clark, E.P. and Samid, D. (1993) Mol. Cell Biol., 13, 4416-4422]. The reduction in ras transcript levels correlated with the extent of GSH depletion and was independent of the specific mode of oncogene activation. Since the activity of p21(ras) is thought to be involved in pathways of T cell activation, we set out to determine whether down-regulation of ras expression in T cells could be the mechanism by which T cell proliferation was inhibited in GSH-depleted T lymphocytes. Despite reducing the GSH level of concanavalin A-activated human peripheral blood mononuclear cells by 66%, no effect on ras mRNA expression was observed. Similarly, no reduction of ras transcript levels were detected in a human T cell line (Jurkat) or in a human monocytic cell line (THP-1) depleted of glutathione. Our results demonstrate that the mechanism by which GSH depletion inhibits T cell proliferation does not appear to involve a decrease in ras mRNA expression. In addition, our results suggest that differences in the regulation of ras mRNA expression may exist between lymphoid/monocytic cells of non-hematopoietic origin.
 ...
PMID:N-ras mRNA expression is unaffected in glutathione-depleted cells of hematopoietic origin. 765 16

The denitration of organic nitrate esters in rabbit hepatic cytosol was characterized. Sephadex G-200 chromatography of ammonium sulfate precipitate (40-80%) from hepatic cytosol demonstrated the presence of two distinct activities (peak I and peak II) responsible for the denitration of nitroglycerin (NTG) and isosorbide dinitrate (ISDN). The denitration of peak I required dithiothreitol (DTT), but not glutathione (GSH), and was not inhibited by S-alkyl GSH, an inhibitor of glutathione S-transferase (GST). Whereas, the denitration activity of peak II was potentiated by GSH, and was inhibited by S-alkyl GSH. These results strongly suggest that the denitration of organic nitrate esters, such as NTG and ISDN, can be catalyzed by at least two enzymes, GSH-independent denitration (peak I) and the GSH-dependent denitration (peak II, GST), in rabbit hepatic cytosol. The denitration activity of peak I was inhibited by SH-modified reagent, indicating that free thiol(s) is (are) critical for expression of the denitration activity. Also, in rabbit vascular cytosol, the cofactor requirement for denitration and response to S-hexyl GSH suggest the participation of GSH-independent enzyme which is responsible for the denitration of organic nitrate esters.
Res Commun Mol Pathol Pharmacol 1995 May
PMID:GSH-independent denitration of organic nitrate esters in rabbit hepatic and vascular cytosol. 767 Aug 47

To clarify the role of glutathione (GSH), an antioxidative substance, and its association with the gastric mucosal defense mechanism, we examined the gastric mucosal GSH and GSH-dependent enzymes in gastric ulcer patients. The subjects of this study were 10 patients with active ulcer on the lesser curvature side in the lower part of the gastric body and 11 normal controls. At the time of gastric endoscopy, gastric mucosal specimens were obtained by routine forceps biopsy from a site several millimeters apart from the ulcer margin, and these specimens were used for measurement of GSH, glutathione peroxidase (GSH-Px), glutathione-S transferase (GST) and gamma-glutamyl transpeptidase (gamma-GTP). The GSH level and the GSH-Px and GST activities in the patients with gastric ulcer were lower than those in the control group. The GSH-Px activity at the healed stage after treatment was increased compared with the pre-treatment value, while the GSH level was not markedly increased and the GST and gamma-GTP activities were similar to the pre-treatment value. The GSH level and GSH-Px activity remained decreased in the non-responder group. These results suggest that gastric mucosal GSH and GSH-dependent enzymes are closely related to the etiology and course of gastric ulcer.
Res Commun Mol Pathol Pharmacol 1995 May
PMID:Changes in glutathione in gastric mucosa of gastric ulcer patients. 767 Aug 48

Mitochondria-rich fractions isolated from livers of rats fed diets differing in their vitamin E (E) and/or selenium (Se) contents were subjected to NADPH/ADP/Fe(3+)- dependent assays of lipid peroxidation. Addition of GSH resulted in an inhibition, or lag period, of lipid peroxidation in mitochondria from rats supplemented with E. This effect was independent of the Se status of the rats. Addition of GSH + GSSG did not potentiate the lag period over that observed with GSH alone. Significant changes in mitochondrial alpha-TH during lipid peroxidation, either in the presence or absence of GSH, were not observed. Total protein thiol (PrSH) content of native mitochondria was lower in rats fed a diet deficient in both E and Se, compared to the other dietary groups. Addition of GSH or GSH + GSSG maintained mitochondrial PrSH at higher levels during lipid peroxidation than in control assays without added GSH/GSSG. Addition of GSSG alone decreased PrSH in mitochondria prepared from all rats regardless of their E or Se status. Reduced ubiquinone-9 (U-9) and the % of total U-9 and U-10 in the reduced form were significantly decreased in liver tissue from rats fed the diet deficient in both E and Se.
Biochem Mol Biol Int 1994 Dec
PMID:Dietary vitamin E and selenium effects on resistance to oxidative stress in rat liver mitochondria. 769 94

The effects of acetaminophen (APAP) on stress-induced gastric mucosal lesions were investigated in rats treated with water-immersion restraint stress (WIR) for 3 hours. Three-hour WIR caused both significant increase in gastric lesions in terms of ulcer index and lipid peroxide levels and decrease in prostaglandin E2 (PGE2) levels in the stomach, compared with prestress control levels. When APAP (500mg/kg) was intraperitoneally (i.p.) administered into rats 2 hours before WIR, the stress-induced changes were significantly inhibited. Whereas, three-hour WIR markedly decreased total glutathione levels in the liver, but not in the stomach and plasma and simultaneously reduced glutathione (GSH) levels in the liver and stomach were markedly decreased. In addition to the enhancement of decrease in liver total glutathione levels, APAP pretreatment caused significant decrease in gastric and plasma total glutathione levels compared with prestress control levels. Moreover, co-administration of indomethacin (5mg/kg, i.p.) with APAP almost abolished the protective effects of APAP against the stress-induced ulceration. These results suggest that APAP may protect gastric mucosa from stress-induced ulceration, probably through the promoted production of PGE2 in the gastric mucosa without restoring glutathione levels.
Res Commun Mol Pathol Pharmacol 1994 Dec
PMID:Effect of acetaminophen on stress-induced gastric mucosal lesions in rats. 771 6

In mice depleted of glutathione (GSH) by pretreatment with an inhibitor of GSH synthesis, buthionine sulfoximine (BSO; 1 hr before styrene, 2 mmol/kg or higher doses, ip), styrene (0.96-5.76 mmol/kg, po) produced hepatotoxicity characterized by an increase in serum alanine transaminase activity and cetrilobular necrosis of hepatocytes. Treatment with inhibitors of hepatic cytochrome P-450-dependent monooxygenases such as carbon disulfide, methoxsalen, piperonyl butoxide, and SKF-525A prevented or tended to reduce the hepatotoxic effect of styrene given in combination with BSO. Styrene 7,8-oxide (3.84 mmol/kg, po), a known metabolite of styrene, in combination with BSO caused an earlier and larger increase in SALT than that caused by an equimolar dose of styrene in combination with BSO. These results suggest that metabolism of styrene, possibly to styrene 7,8-oxide, is a necessary step in styrene-induced hepatotoxicity in GSH-depleted mice. Before the onset of hepatotoxicity, styrene in combination with BSO produced a larger and more prolonged depletion of hepatic GSH than that seen after the sole treatment with BSO or prolonged depletion of hepatic GSH than that seen after the sole treatment with BSO or styrene, but no depletion of hepatic protein sulfhydryls was induced by styrene in combination with BSO.
Res Commun Mol Pathol Pharmacol 1994 Dec
PMID:Styrene-induced hepatotoxicity in mice depleted of glutathione. 771 12


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