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Inhibition by zinc of deoxycholate‐induced apoptosis in HCT‐116 cells
Author(s) -
Smith Abigail F.,
Longpre Jennifer,
Loo George
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23394
Subject(s) - apoptosis , programmed cell death , reactive oxygen species , zinc , chemistry , mitochondrion , microbiology and biotechnology , cytochrome c , fragmentation (computing) , cell , caspase , dna fragmentation , biology , biochemistry , ecology , organic chemistry
The bile acid, deoxycholate, can induce apoptosis although the effect of trace elements on such cell death is unknown. The aim of this study was to determine if deoxycholate‐induced apoptosis is influenced by zinc. HCT‐116 colon epithelial cells were pre‐treated with zinc and then exposed to deoxycholate. Membrane blebbing, formation of apoptotic bodies, and greater overall production of reactive oxygen species (ROS) occurred in cells exposed to deoxycholate, but zinc inhibited the occurrence of these three events caused by deoxycholate. Upon finer analysis, stimulation of mitochondrial superoxide production, mitochondrial dysfunction, and cytochrome c release were detected in cells exposed to deoxycholate, but zinc did not inhibit any of these three effects caused by deoxycholate. Additionally, caspase‐3 activation, plasma membrane phospholipid translocation, and also chromatin condensation and fragmentation were observed in cells exposed to deoxycholate, but all of these effects of deoxycholate, including the greater overall ROS production, were all inhibited by zinc. Because zinc did not prevent the three mitochondrial effects caused by deoxycholate, the last set of findings suggested that zinc hampered activation of an initiator caspase upstream of effector caspase‐3, in inhibiting deoxycholate‐induced HCT‐116 cell death. In examining this possibility, it was found that caspase‐8 activation caused by deoxycholate was blocked by zinc. Collectively, the results suggest that zinc can inhibit deoxycholate‐induced apoptotic cell death mediated by caspases. J. Cell. Biochem. 113: 650–657, 2012. © 2011 Wiley Periodicals, Inc.