GLUTATHIONE-PEROXIDASE, SUPEROXIDE-DISMUTASE, AND CATALASE INACTIVATION BY PEROXIDES AND OXYGEN DERIVED FREE-RADICALS

GLUTATHIONE-PEROXIDASE, SUPEROXIDE-DISMUTASE, AND CATALASE INACTIVATION BY PEROXIDES AND OXYGEN DERIVED FREE-RADICALS
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DOI:
10.1016/0047-6374(90)90078-t
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发表时间:
1990-02-15
影响因子:
5.3
通讯作者:
REMACLE, J
REMACLE, J
中科院分区:
医学3区
文献类型:
--
作者:
PIGEOLET, E;CORBISIER, P;REMACLE, J

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谷胱甘肽过氧化物酶(GPX)、超氧化物歧化酶(SOD)和过氧化氢酶是细胞抗氧化防御系统中最重要的酶。然而,这些分子本身很容易被氧化。这项工作的目的是估计该系统在多大程度上可以被其自身的底物失活。我们测试了过氧化氢、氢过氧化异丙苯、氢过氧化叔丁基以及GPX、SOD 和过氧化氢酶的羟基和超氧自由基的作用。对于GPX,对于过氧化氢,在10-1M(30分钟,37℃)下观察到50%失活,3次。氢过氧化异丙苯为 10-4 M(15 分钟,37°C),5 次。叔丁基氢过氧化物为10-5 M(11分钟,37℃)。与羟基自由基不同,超氧阴离子不会使这种酶失活。过氧化氢酶被羟基自由基和超氧阴离子灭活,但有机过氧化物没有作用。 4次过氧化氢使SOD失活50%。 10-4 M(20分钟,37℃),但有机过氧化物和羟基自由基对此酶无效。由于抗氧化系统的三种酶对至少一种氧化反应分子敏感,在高氧化应激的情况下,可能会发生这种抑制,导致不可逆的自催化过程,其中氧化剂的生产率将不断增加,导致细胞死亡。
Glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase are the most important enzymes of the cell antioxidant defense system. However, these molecules are themselves susceptible to oxidation. The aim of this work was to estimate to what extent this system could be inactivated by its own substrates. We tested the effect of hydrogen peroxide, cumene hydroperoxide, t-butyl hydroperoxide and hydroxyl and superoxide radicals of GPX, SOD and catalase. For GPX, a 50% inactivation was observed at 10-1 M (30 min, 37.degree. C) for hydrogen peroxide, 3 .times. 10-4 M (15 min, 37.degree. C) for cumene hydroperoxide and 5 .times. 10-5 M (11 min, 37.degree. C) for t-butyl hydroperoxide. Unlike the hydroxyl radicals, superoxide anions did not inactivate this enzyme. Catalase was inactivated by hydroxyl radicals and by superoxide anions but organic peroxides had no effect. SOD was inactivated by 50% by hydrogen peroxide at 4 .times. 10-4 M (20 min, 37.degree.C), but organic peroxides and hydroxyl radicals were ineffective on this enzyme. Since the three enzymes of the antioxidant system are susceptible to at least one of the oxidative reactive molecules, in the case of high oxidative stresses such an inhibition could take place, leading to an irreversible autocatalytical process in which the production rate of the oxidants will continuously increase, leading to cell death.