Modulation of caspase-3 activity by zinc ions and by the cell redox state
Modulation of caspase-3 activity by zinc ions and by the cell redox state
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DOI：
10.1006/excr.2001.5222
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发表时间：
2001-06-10
影响因子：
3.7
通讯作者：
Poirier, GG
中科院分区：
文献类型：
--
作者：
Marini, M;Frabetti, F;Poirier, GG
已知细胞凋亡过程中的DNA片段化受多种因素控制，其中一个关键步骤是DNA酶抑制剂ICAD的半胱天冬酶操作切割。我们以前已经证明，过氧化氢处理的淋巴细胞进行细胞凋亡而不形成DNA梯状条带;然而，使用微摩尔量的Zn 2+螯合剂允许DNA裂解在internucleosomal网站。这些结果在本工作中得到了扩展，从而使其框架与细胞氧化还原状态的改变有关。过氧化氢处理的淋巴细胞中的细胞凋亡被发现发生与caspase-3激活，但酶的活性被发现受损，从而影响internucleosomal碎片以及核形态。Caspase-3的活性被发现恢复后，温和的Zn 2+螯合。这些结果也提供了一个实验模型，从中可以检查caspase-3活性上游和下游的凋亡事件。(C)北京：科学出版社.
It is known that DNA fragmentation during apoptosis is controlled by a number of factors, a crucial step being the caspase-operated cleavage of ICAD, the DNase inhibitor. We have previously demonstrated that hydrogen peroxide-treated lymphocytes undergo apoptosis without formation of a DNA ladder; however, the use of micromolar amounts of a Zn2+ chelator allowed DNA cleavage at internucleosomal sites. Such results were extended in the present work, thus allowing their framing into the events related to alterations in the redox state of the cell. Apoptosis in hydrogen peroxide-treated lymphocytes was found to occur with caspase-3 activation, but the enzyme activity was found to be impaired, thus affecting internucleosomal fragmentation as well as nuclear morphology. Caspase-3 activity was found to resume upon mild Zn2+ chelation. These results provide as well an experimental model from which apoptotic events upstream and downstream of caspase-3 activity can be examined. (C) 2001 Academic Press.