Exp Mol Med.
2006 Dec;38(6):634-642.
zVAD-fmk, unlike BocD-fmk, does not inhibit caspase-6 acting on 14-3-3/Bad pathway in apoptosis of p815 mastocytoma cells
- Affiliations
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- 1Department of Anatomy and Cell Biology (BK21 program), Dong-A University College of Medicine and Medical Science Research Center, Busan 602-714, Korea. yhyoo@dau.ac.kr
- 2Department of Physiology, Dong-A University College of Medicine and Medical Science Research Center, Busan 602-714, Korea
- 3Department of Biological Sciences, Kosin University, Busan 606-701, Korea
- 4College of Dentistry and Research Institute for Oral Biotechnology, Pusan National University, Busan 602-739, Korea
- 5Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701, Korea
Abstract
- In a preliminary study, we found that benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD- fmk), unlike Boc-aspartyl(OMe)-fluoromethylketone (BocD-fmk), at usual dosage could not prevent genistein-induced apoptosis of p815 mastocytoma cells. This study was undertaken to reveal the mechanism underlying the incapability of zVAD-fmk in preventing this type of apoptosis. We observed that 14-3-3 protein level was reduced in genistein-treated cells and that BocD-fmk but not zVAD-fmk prevented the reduction of 14-3-3 protein level and the release of Bad from 14-3-3. We also demonstrated that truncated Bad to Bcl-xL interaction in genistein- treated cells was prevented by BocD-fmk but not by zVAD-fmk treatment. Our data indicate that BocD- fmk, compared to zVAD-fmk, has a certain preference for inhibiting 14-3-3/Bad signalling pathway. We also elucidated that this differential efficacy of BocD-fmk and zVAD-fmk resulted from the different effect in inhibiting caspase-6 and that co-treatment of zVAD-fmk and caspase-6 specific inhibitor substantially prevented genistein-induced apoptosis. Our data shows that caspase-6 plays a role on Bad/14-3-3 pathway in genistein-induced apoptosis of p815 cells, and that the usual dose of zVAD-fmk, in contrast to BocD-fmk, did not prevent caspase-6 acting on 14-3-3/Bad-mediated event.
Keyword
MeSH Terms
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bcl-Associated Death Protein/*metabolism
*Signal Transduction/drug effects
Mitochondria/drug effects
Mice
Mastocytoma
Hydrocarbons, Fluorinated/*pharmacology
Genistein/pharmacology
Enzyme Inhibitors/*pharmacology
Cell Line, Tumor
Caspase 6/antagonists & inhibitors/*metabolism
Benzyl Compounds/*pharmacology
Apoptosis/*drug effects
Animals
Amino Acid Chloromethyl Ketones/pharmacology
14-3-3 Proteins/*metabolism
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