Caspases are reversibly inactivated by hydrogen peroxide

Caspases are reversibly inactivated by hydrogen peroxide
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DOI:
10.1016/s0014-5793(01)02593-5
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发表时间:
2001-07-06
期刊:
影响因子:
3.5
通讯作者:
Brown, GC
Brown, GC
中科院分区:
生物学3区
文献类型:
--
作者:
Borutaite, V;Brown, GC

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过氧化氢(H2 O2)是已知的诱导和抑制细胞凋亡,但机制尚不清楚。我们发现,H_2O_2抑制重组caspase-3和caspase-8的活性,在约17 μ M H_2O_2时出现半抑制,这种抑制作用可被二硫苏糖醇阻止和逆转,而谷胱甘肽几乎没有保护作用,在一氧化氮诱导caspase活化或血清戒断后加入100-200 μ M H_2O_2可显著抑制caspase活性。在巨噬细胞中产生H2 O2的NADPH氧化酶的活化也引起细胞半胱天冬酶的过氧化氢酶敏感性失活。这些数据表明,在细胞中的半胱天冬酶的活性可以直接但可逆地抑制过氧化氢。(C)2001年欧洲生物化学学会联合会。由Elsevier Science B. V.出版,版权所有。
Hydrogen peroxide (H2O2) is known to both induce and inhibit apoptosis, however the mechanisms are unclear. We found that H2O2 inhibited the activity of recombinant caspase-3 and caspase-8, half-inhibition occurring at about 17 muM H2O2, This inhibition was both prevented and reversed by dithiothreitol while glutathione had little protective effect, 100-200 muM H2O2 added to macrophages after induction of caspase activation by nitric oxide or serum withdrawal substantially inhibited caspase activity. Activation of H2O2-producing NADPH oxidase in macrophages also caused catalase-sensitive inactivation of cellular caspases. The data suggest that the activity of caspases in cells can be directly but reversibly inhibited by H2O2. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.