Activation of caspase-3-like protease by digitonin-treated lysosomes

Activation of caspase-3-like protease by digitonin-treated lysosomes
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DOI:
10.1016/s0014-5793(98)01080-1
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发表时间:
1998-09-18
期刊:
影响因子:
3.5
通讯作者:
Utsumi, K
Utsumi, K
中科院分区:
生物学3区
文献类型:
--
作者:
Ishisaka, R;Utsumi, T;Utsumi, K

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细胞凋亡是一种自然发生的细胞程序性死亡或细胞“自杀”,是组织形态发生和组织重建的重要机制之一。半胱氨酸天冬氨酸蛋白酶(caspase)的激活是导致细胞凋亡的关键步骤之一。虽然caspase-3的激活机制之一是由caspase介导的,但另一个亚细胞区室可能参与了该酶的激活。本研究表明,毛地黄皂苷处理的溶酶体的上清液部分强烈激活Ac-DEVD-CHO可降解的caspase-3样蛋白酶,毛地黄皂苷处理的溶酶体部分对caspase-3样蛋白酶的激活被半胱氨酸蛋白酶抑制剂hy leupeptin和E-64特异性抑制,这些结果表明,溶酶体半胱氨酸蛋白酶泄漏到胞质区室可能参与半胱天冬酶-3样蛋白酶的激活,(C)1998年欧洲生物化学学会联合会。
Apoptosis, a naturally occurring programmed cell death or cell 'suicide', has been paid much attention as one of the critical mechanisms for morphogenesis and tissue remodeling. Activation of cysteine aspartases (caspases) is one of the critical steps leading to apoptosis, Although a mitochondria-mediated pathway has been postulated to be one of the activation mechanism of caspase-3, another subcellular compartment might be involved in the activation of the enzyme. The present study shows that the supernatant fraction of digitonin-treated lysosomes strongly activates Ac-DEVD-CHO inhibitable caspase-3-like protease, Activation of caspase-3-like protease by digitonin-treated lysosomal fractions was specifically suppressed hy leupeptin and E-64, inhibitors of cysteine protease, These results indicate that leakage of lysosomal cysteine protease(s) into the cytosolic compartment might be involved in the activation of caspase-3-like protease, (C) 1998 Federation of European Biochemical Societies.