Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of reactive oxygen intermediates generated by hypoxanthine plus xanthine oxidase on the Ca(2+)-adenosinetriphosphatase (ATPase) of sarcoplasmic reticulum from bovine aortic smooth muscle were studied. Exogenous hypoxanthine (0.1-100 microM) plus xanthine oxidase (10 mU/ml) produced an hypoxanthine concentration-dependent inhibition of the Ca(2+)-ATPase. The inhibition could be completely blocked by superoxide dismutase (100 U/ml) but not by either mannitol (20 mM) or deferoxamine (100 microM). Direct addition of hydrogen peroxide in the micromolar range did not cause significant inhibition. These results suggest that superoxide is the primary damaging species. Cysteine blocked this inhibition, suggesting possible involvement of sulfhydryl groups in the inhibition mechanism. Additionally, 1.16 +/- 0.17 mU/g wet wt of xanthine oxidase activity was detected in the postnuclear supernatant of bovine aortic smooth muscle, suggesting the existence of a possible intracellular source of superoxide. This value was calculated to be approximately 5 mU/ml by using a usual value of vascular smooth muscle cellular volume. Thus the level of endogenous xanthine oxidase in vascular smooth muscle is comparable with the level of exogenous xanthine oxidase used in the present study. These findings suggest a potential role of xanthine oxidase-generated superoxide in oxidative damage to vascular smooth muscle during a number of pathophysiological conditions.
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PMID:Inhibition of Ca(2+)-ATPase of vascular smooth muscle sarcoplasmic reticulum by reactive oxygen intermediates. 183 1

Although oxygen free radicals have been implicated as mediators of cellular injury in myocardial ischemia-reperfusion, the exact nature of defects produced by these radicals is not clear. Because sarcolemmal Ca2+-pump is involved in the efflux of Ca2+ from the cell, this study was undertaken to examine the effects of oxygen free radicals on sarcolemmal ATP-dependent Ca2+ accumulation and Ca2+-stimulated Mg2+-dependent adenosinetriphosphatase (ATPase) activities as well as lipid peroxidation of membrane phospholipids. Isolated rat heart sarcolemmal membranes were incubated with xanthine + xanthine oxidase [a superoxide anion radical (O2-)-generating system], H2O2, or H2O2 + Fe2+ [a hydroxyl radical (HO.)-generating system] and assayed for Ca2+-pump activities. O2- inhibited the Ca2+-pump activities in a time-dependent manner; a significant inhibition of Ca2+-stimulated ATPase activity was seen after 1 min of incubation. Superoxide dismutase showed a protective effect on depression in Ca2+-pump activities caused by O2-.H2O2 inhibited Ca2+-pump activities in a dose-dependent manner; this inhibition was protected by the addition of catalase. HO. depressed the Ca2+-pump activities to a greater extent in comparison with H2O2. Mannitol showed a protective effect on HO.-induced inhibition of Ca2+-pump activities. The promotion of lipid peroxidation by free radicals was evident from increased formation of malondialdehyde. These results indicate that the sarcolemmal membrane is altered on exposure to oxygen free radicals, and this may result in depressing the Ca2+-pump mechanism for Ca2+ efflux from the myocardial cell.
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PMID:Depression of heart sarcolemmal Ca2+-pump activity by oxygen free radicals. 253 32

To understand the involvement of changes in sulfhydryl groups in causing depression of the sarcolemmal Ca2+-pump activities, this study was undertaken to examine the effects of oxygen free radicals on rat heart sarcolemmal sulfhydryl groups, Ca2+-stimulated adenosinetriphosphatase (ATPase), and ATP-dependent Ca2+ accumulation. In addition, the effects of sulfhydryl reagents such as dithiothreitol, cysteine, and N-ethylmaleimide on Ca2+-pump activities were investigated. The inhibition of sarcolemmal Ca2+-pump activities by O2-. (xanthine + xanthine oxidase) and H2O2 was decreased by the addition of dithiothreitol or cysteine in a dose-dependent manner. N-ethylmaleimide also showed inhibitory effects on Ca2+-pump activities both in a dose- and time-dependent manner; dithiothreitol and cysteine prevented changes in Ca2+-pump activities because of N-ethylmaleimide. Heart sarcolemmal sulfhydryl groups were depressed by O2-., H2O2, and .OH (H2O2 + Fe2+) both in a dose- and time-dependent manner. Superoxide dismutase, catalase, and D-mannitol showed protective effects on the sulfhydryl group depression by O2-., H2O2, and .OH, respectively. A significant correlation between changes in sarcolemmal Ca2+-stimulated ATPase activity and sarcolemmal sulfhydryl groups was seen. These results indicate that oxygen free radicals may depress the heart sarcolemmal Ca2+-pump activities by modifying the sulfhydryl groups in the sarcolemmal membrane.
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PMID:Mechanism for depression of heart sarcolemmal Ca2+ pump by oxygen free radicals. 255 Nov 90