| zVAD-fmk, unlike BocD-fmk, does not inhibit caspase-6 acting on 14-3-3/Bad pathway in apoptosis of p815 mastocytoma cells. | |
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MedLine Citation:
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PMID: 17202839 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Su-Bog Yee; Soo Jin Baek; Hwan Tae Park; Seung Hun Jeong; Jin Hee Jeong; Tae Hyun Kim; Jong-Min Kim; Byung Kap Jeong; Bong Soo Park; Taeg Kyu Kwon; Il Yoon; Young Hyun Yoo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental & molecular medicine Volume: 38 ISSN: 1226-3613 ISO Abbreviation: Exp. Mol. Med. Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2007-01-04 Completed Date: 2007-01-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9607880 Medline TA: Exp Mol Med Country: Korea (South) |
Other Details:
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Languages: eng Pagination: 634-42 Citation Subset: IM |
Affiliation:
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Department of Anatomy and Cell Biology (BK21 program), Dong-A University College of Medicine and Medical, Science Research Center, Busan 602-714, Korea. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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14-3-3 Proteins
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metabolism* Amino Acid Chloromethyl Ketones / pharmacology Animals Apoptosis / drug effects* Benzyl Compounds / pharmacology* Caspase 6 / antagonists & inhibitors, metabolism* Cell Line, Tumor Enzyme Inhibitors / pharmacology* Genistein / pharmacology Hydrocarbons, Fluorinated / pharmacology* Mastocytoma Mice Mitochondria / drug effects Signal Transduction* / drug effects bcl-Associated Death Protein / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/14-3-3 Proteins; 0/Amino Acid Chloromethyl Ketones; 0/Benzyl Compounds; 0/Boc-D-FMK; 0/Enzyme Inhibitors; 0/Hydrocarbons, Fluorinated; 0/bcl-Associated Death Protein; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 446-72-0/Genistein; EC 3.4.22.-/Caspase 6 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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