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

Norcocaine nitroxide was found to be produced via the one-electron oxidation of N-hydroxynorcocaine by hepatic microsomal enzymes from induced and noninduced rats, hamsters, and mice in the presence of an NADPH-generating system. This reaction was demonstrated to be mediated by cytochrome P-450 as suggested by induction experiments using phenobarbital, which markedly enhanced the production of this nitroxide, and by the inhibition of this monooxygenase by metyrapone, which depressed the formation of this free radical. Unlike other nitroxides, norcocaine nitroxide was rapidly reduced by flavoproteins such as cytochrome P-450 reductase and FAD-monooxygenase, but not cytochrome P-450. We believe that since NADPH is consumed during the futile cycling of N-hydroxynorcocaine/norcocaine nitroxide and since NADPH is an essential cofactor of the glutathione reductase system, diminished reduced nucleotide may lead to depressed levels of cellular glutathione. In this manner, we theorize that cocaine initiates hepatotoxicity.
Mol Pharmacol 1982 Mar
PMID:Norcocaine nitroxide. A potential hepatotoxic metabolite of cocaine. 709 46

Bioluminescence photokinetic assay of NADP+ is described, using the glucose-6-phosphate dehydrogenase reaction for conversion to its reduced form and subsequent measurement of this with luciferase extracts of Vibria fisherii. the analyses were applied to the determination of the activity of minute amounts of glutathione reductase using NADP+ as measurable product and for nucleotide assay in cell samples of 0.5--10 microgram dry weight. The sensitivity was sufficient for determining 0.5 picomoles NADP+. Previously, FMN, NADH, NAD+ and NADH have been analysed with the bacterial luciferase system. Its applicability has not been extended by the assay of NADP+.
Mol Cell Biochem 1980 Aug 29
PMID:Photokinetic microanalysis of NADP+, using bacterial luciferase. 744 56

Because alveolar macrophages generate and release reactive oxygen metabolites but also contain antioxidative enzymes, they have the potential of either damaging or protecting tissues. We investigated the relative role of the hydrogen peroxide (H2O2)-scavenging antioxidative enzymes in H2O2 disposal and cell protection using freshly isolated (5 h ex vivo) and overnight (24 h ex vivo) cultured human alveolar macrophages. Cell protection was assessed on the basis of maintenance of cellular high-energy phosphates, leakage of intact nucleotides into the extracellular medium, and appearance of the nucleotide catabolic products xanthine, hypoxanthine, and uric acid. To investigate the relative importance of catalase and the glutathione redox cycle, the experiments were conducted in cells pretreated with amino-triazole (ATZ) to inactivate catalase or with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to inactivate glutathione reductase. Catalase, glutathione peroxidase, and glutathione reductase activities did not change significantly during overnight culture of the cells. Both freshly isolated and cultured cells consumed exogenous H2O2 mainly by the catalase-dependent pathway. When the cells were exposed to H2O2 (100 microM), catalase and the glutathione redox cycle equally participated in maintaining cellular high-energy nucleotides. However, when cultured cells were exposed to formylated peptide (FMLP) (10(-7) M), the glutathione redox cycle was responsible for the maintenance of high-energy nucleotides. Furthermore, in both exposures, the glutathione redox cycle was more important in maintaining cell membrane integrity and preventing nucleotide leakage from the cells. Immunocytochemical labeling showed that catalase was primarily localized in the peroxisomal compartment of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1995 Oct
PMID:Catalase and glutathione reductase protection of human alveolar macrophages during oxidant exposure in vitro. 754 73

Glutathione reductase participates in preventing lipid peroxidation by oxygen radicals which results in cellular damage. The brain is among the organs most susceptible to cadmium-induced lipid peroxidation. The mechanism of free radical generation by Cd2+ is not well understood, but it is known that Cd2+ is an inhibitor of glutathione reductase. In this study, inhibition kinetics of the brain glutathione reductase by Cd2+ was investigated. Sheep brain enzyme (11,000-fold purified) was used for this purpose. The data were analyzed by a nonlinear curve fitting program. It was found that the inhibition was competitive with respect to oxidized glutathione and uncompetitive with respect to NADPH. Inhibition constants were found as 12.3 and 9.4 muM, respectively. These findings might contribute to the understanding of the mechanism of lipid peroxidation by Cd2+ in brain.
Biochem Mol Med 1995 Feb
PMID:Inhibition kinetics of sheep brain glutathione reductase by cadmium ion. 755 14

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

Visceral leishmaniasis has been found to be associated with severe anemia and premature lysis of erythrocytes. Peroxidative damage of red cells has been noted in several hemolytic anemias. Present study shows enhanced formation of methemoglobin in hamsters infected with Leishmania donovani. Increased formation of malonyldialdehyde and diene conjugate has been noted in the erythrocytes of the infected animals with the progress of anemia. Results showed decreased activities of protective enzymes like superoxide dismutase, catalase and glutathione reductase against peroxidative attack. An increase in the membrane cholesterol/phospholipid ratio and a decrease in membrane fluidity of erythrocytes were observed under the diseased condition. Densitometric scan after SDS-PAGE of red cell membrane of the infected animals revealed significant degradation of band 3 and band 4.1 proteins. The results suggest that alteration in the membrane may lead to reduced life span of the red cells in experimental visceral leishmaniasis.
Mol Cell Biochem 1995 May 24
PMID:Lipid peroxidation of erythrocytes during anemia of the hamsters infected with Leishmania donovani. 756 50

A very potent competitive inhibitor of mammalian glyoxalase II activity, N,S-bis-fluorenylmethoxycarbonylglutathione (DiFMOC-G) has been synthesized and characterized. The Ki value for inhibition of glyoxalase II purified from calf liver is 0.08 microM. The Ki values for glyoxalase I inhibitions range from 285 to 500 fold higher than the values obtained for glyoxalase II inhibitions, depending on the source of the enzyme. Among other enzymes involved in glutathione metabolism, such as glutathione S-transferase, glutathione reductase, and glutathione peroxidase, only glutathione S-transferase is inhibited to a small extent by DiFMOC-G. Diesters of DiFMOC-G were prepared in order to improve transport of DiFMOC-G into mammalian tumor cells (rat adrenal pheochromocytoma, PC-12) in culture. Among the diesters synthesized, diisopropyl DiFMOC-G was found to be the most inhibitory to cell viability, with a [I]0.5 value of 3 microM.
Biochem Mol Biol Int 1995 Apr
PMID:N,S-bis-fluorenylmethoxycarbonylglutathione: a new, very potent inhibitor of mammalian glyoxalase II. 762 27

Yeast glutathione reductase was inactivated by pyridoxal 5'-phosphate. The inhibition was reversed by dilution. The enzyme-pyridoxal 5'-phosphate complex on reduction with sodium borohydride gave a characteristic absorption maximum at 325 nm and fluorescence maximum at 395 nm when exciated at 325 nm. These results were consistent with the reaction of epsilon-amino group of lysine residue of the enzyme with pyridoxal 5'-phosphate. The enzyme was protected against pyridoxal 5'-phosphate inhibition by NADP indicating thereby that the essential lysine residues are present during the NADP binding site.
Biochem Mol Biol Int 1995 Jun
PMID:Essential lysine residue in glutathione reductase: chemical modification by pyridoxal 5'-phosphate. 766 38

The involvement of reactive oxygen species in chromate-induced genotoxicity has been postulated. Because intracellular antioxidants help in eliminating the reactive species of oxygen, we have investigated both the prooxidant and antioxidant status of human leukemic T-lymphocyte MOLT4 cells exposed to nontoxic levels of chromium(VI) in culture. The cells treated with 0-->200 microM potassium chromate in a salts/glucose medium for 2 h were found to contain significantly lower levels of both small molecular weight and macromolecular antioxidants. In particular, the levels of glutathione and ascorbate were found to decrease with increased doses of chromate exposure in a dose-dependent manner. As little as 10 microM chromate was found to decrease these small molecular weight antioxidants significantly (p < 0.01). The macromolecular antioxidants, such as glutathione peroxidase, catalase, glutathione reductase, glucose-6-phosphate dehydrogenase and superoxide dismutase were also significantly (p < 0.01) decreased by exposing the cells to as little as 10 microM chromate. Concomitantly, there was a dose-dependent increase in intracellular H2O2 accumulation in cells exposed to chromium(VI). These results indicate that chromate-induced genotoxicity may be due, at least in part, to decreased levels of intracellular antioxidants in conjunction with an increased production of the reactive oxygen species.
Mol Cell Biochem 1995 Jan 12
PMID:Alterations in the prooxidant and antioxidant status of human leukemic T-lymphocyte MOLT4 cells treated with potassium chromate. 775 43

Adaptation to various forms of stress has been found to be associated with increased cellular tolerance to myocardial ischemia. In this study, the effects of myocardial adaptation to oxidative stress was examined by injecting rats with endotoxin (0.5 mg/kg) and its non-toxic derivative, lipid A (0.5 mg/kg). Both compounds exerted oxidative stress within 1 h of treatment as evidenced by enhanced malonaldehyde formation. The oxidative stress disappeared steadily and progressively with time in concert with the appearance of the induction of glutathione and antioxidative enzymes that included superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. After 24 h of endotoxin or lipid A treatment, the amount of oxidative stress and antioxidant enzyme levels were significantly lower and higher, respectively, compared to those at the baseline levels. Corroborating these results, both endotoxin and lipid A provided protection against myocardial ischemia and reperfusion injury as evidenced by a significantly improved postischemic recovery of left ventricular functions. The data presented here demonstrates that a controlled amount of oxidative stress induces the expression of intracellular antioxidants that can result in enhanced myocardial tolerance to ischemia. This suggests that myocardial adaptation to oxidative stress may be a potential tool for reduction of ischemic/reperfusion injury.
Mol Cell Biochem 1995 Mar 09
PMID:Oxidative stress adaptation improves postischemic ventricular recovery. 779 47


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