Dual regulation of caspase activity by hydrogen peroxide: Implications for apoptosis

Dual regulation of caspase activity by hydrogen peroxide: Implications for apoptosis
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DOI:
10.1016/s0014-5793(97)01068-5
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发表时间:
1997-09-15
期刊:
影响因子:
3.5
通讯作者:
Orrenius, S
Orrenius, S
中科院分区:
生物学3区
文献类型:
--
作者:
Hampton, MB;Orrenius, S

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50 μ M过氧化氢诱导Jurkat t淋巴细胞凋亡与caspase激活相关,处理后3 h首次检测到caspase活性,6 h凋亡形态学特征明显,高浓度过氧化氢处理后,caspase活性消失,细胞坏死死亡。用过氧化氢处理的细胞经历fas介导的凋亡的能力受损,这似乎是直接抑制半胱氨酸依赖的半胱氨酸酶的结果,细胞只能恢复并在以后的时间进行凋亡,因此,过氧化氢有两个不同的作用,它最初抑制半胱氨酸酶和延迟凋亡,然后,根据初始氧化应激的程度,半胱氨酸酶被激活,细胞凋亡死亡。我们讨论了细胞在凋亡过程中必须维持还原环境以允许半胱天蛋白酶发挥作用的生理意义。(C) 1997年欧洲生化学会联合会。
The induction of apoptosis in Jurkat T-lymphocytes with 50 mu M hydrogen peroxide was associated with caspase activation, Caspase activity was first detected 3 h after treatment, and the morphological features of apoptosis were apparent by 6 h, At higher concentrations of hydrogen peroxide there,vas no detectable caspase activity, and the cells died by necrosis. Cells treated with hydrogen peroxide were impaired in their ability to undergo Fas-mediated apoptosis, This appeared to be the result of direct inhibition of the cysteine-dependent caspases, The cells mere able to recover and undergo apoptosis at later times, Therefore, hydrogen peroxide has two distinct effects, It initially inhibits the caspases and delays apoptosis, Then, depending on the degree of the initial oxidative stress, the caspases are activated and the cells die by apoptosis, or they remain inactive and necrosis occurs, We discuss the physiological implications of cells having to maintain a reducing environment during apoptosis to allow the caspases to function. (C) 1997 Federation of European Biochemical Societies.