Redistribution of activated caspase-3 to the nucleus during butyric acid-induced apoptosis

被引:36
作者
Mandal, M [1 ]
Adam, L [1 ]
Kumar, R [1 ]
机构
[1] Univ Texas, Cell Growth Regulat Lab, MD Anderson Canc Ctr, Houston, TX 77030 USA
关键词
D O I
10.1006/bbrc.1999.0966
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The colonic epithelial cells near the top of the crypt and in the lumen have been shown to undergo apoptosis. Since butyric acid is the major short-chain fatty acid produced by fermentation of dietary fiber in the large bowel, it has been proposed that it could act as an important regulator of apoptosis in colorectal cancer. Here we report that in cells treated with butyric acid, the cleavage of DNA-PKcs was paralleled or preceded by the induction of activation of caspase-3, and these events were inhibited by Bcl-2 overexpression. We also demonstrated the redistribution of activated caspase-3 to the nuclear compartment where it locally cleaves DNA-PKcs and poly(ADP-ribose) polymerase, and cleaved fragments were released in the cytosolic compartment. The observed activation of caspase-3 and nuclear cleavage of its substrates and their subsequent release into the cytosol were inhibited by a specific caspase-3 inhibitor, the tetrapeptide DEVD-CHO. These findings suggest that relocalization of activated caspase-3 to the nucleus may constitute an important apoptotic signal during butyric acid-induction of apoptosis human colorectal cancer cells. (C) 1999 Academic Press.
引用
收藏
页码:775 / 780
页数:6
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