Document Detail

Clofibrate-induced apoptosis is mediated by Ca2+-dependent caspase-12 activation.
MedLine Citation:
PMID:  16236330     Owner:  NLM     Status:  MEDLINE    
The mechanism of fibrate-induced myopathy was investigated in this report. When clofibrate (30 to 300 microM) was applied to L6 rat skeletal myoblasts, dose-dependently apoptosis was observed within 24 h. In the apoptotic myoblasts, a caspase-12 cleavage was observed at 2 h and with following caspases-9 and -3-related cascade activation. In contrast, the neutral protease calpain, that is a key enzyme in ER stress-related apoptosis via caspase-12 activation, was significantly decreased during apoptosis. Next, the authors evaluated a role of calcium-dependent signal(s). When clofibrate was added into medium, cytosolic calcium concentration was rapidly and persistently increased. On the other hand, an addition of 10 mM EGTA depressed sustained calcium phase, and concurrent myoblasts apoptosis was completely inhibited. Taken together, our findings indicate that the clofibrate-induced myopathy is triggered by Ca2+ influx, then activated cytosolic caspase-12 through calpain-independent cascade, and consequently caused apoptotic DNA fragmentation.
Sumio Matzno; Shinya Yasuda; Yuka Kitada; Takeshi Akiyoshi; Naoko Tanaka; Sachiko Juman; Kazumasa Shinozuka; Toshikatsu Nakabayashi; Kenji Matsuyama
Publication Detail:
Type:  Journal Article     Date:  2005-10-19
Journal Detail:
Title:  Life sciences     Volume:  78     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-28     Completed Date:  2006-04-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1892-9     Citation Subset:  IM    
First Department of Biochemistry, School of Pharmaceutical Sciences, Mukogawa Women's University, 11-68, Koshien, Nishinomiya, Hyogo 663-8179, Japan.
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MeSH Terms
Antilipemic Agents / pharmacology*
Apoptosis / drug effects*
Calcium / pharmacology*
Calpain / pharmacology
Caspase 12
Caspase 3
Caspase 9
Caspases / metabolism*
Cells, Cultured
Chelating Agents / pharmacology
Clofibrate / pharmacology*
Cytosol / enzymology
Egtazic Acid / pharmacology
Enzyme Activation
Muscle, Skeletal / cytology,  drug effects,  metabolism
Reg. No./Substance:
0/Antilipemic Agents; 0/Casp12 protein, rat; 0/Chelating Agents; 637-07-0/Clofibrate; 67-42-5/Egtazic Acid; 7440-70-2/Calcium; EC 3.4.22.-/Calpain; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Casp9 protein, rat; EC 3.4.22.-/Caspase 12; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases

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