期刊
EXPERIMENTAL CELL RESEARCH
卷 315, 期 2, 页码 327-335出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2008.10.041
关键词
Apoptosis; Hypoxia; p38; Caspase; DNA ladder formation; Chromatin condensation; Nuclear fragmentation
资金
- Japan Society for the Promotion of Sciences (JSPS)
We recently reported that a broad-spectrum caspase inhibitor zVAD-fmk failed, while p38 inhibitor SB203580 succeeded, to prevent chromatin condensation and nuclear fragmentation induced by hypoxia in tube-forming HUVECs. In this study, we investigated the reasons for zVAD-fmk's inability to inhibit these morphological changes at the molecular level. The inhibitor effectively inhibited DNA ladder formation and activation of caspase-3 and -6, but it surprisingly failed to inhibit caspase-7 activation. On the other hand, SB203580 successfully inhibited all of these molecular events. When zLEHD-fmk, which specifically inhibits initiator caspase-9 upstream of caspase-3, was used, it inhibited caspase-3 activation but failed to inhibit caspase-6 and -7 activation. It also failed to inhibit hypoxia-induced chromatin condensation, nuclear fragmentation and DNA ladder formation. Taken together, our results indicate that, during hypoxia, caspase-7 is responsible for chromatin condensation and nuclear fragmentation while caspase-6 is responsible for DNA ladder formation. (C) 2008 Elsevier Inc. All rights reserved.
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