Document Detail


Calpain protects the heart from hemodynamic stress.
MedLine Citation:
PMID:  21795695     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Calpains make up a family of Ca(2+)-dependent intracellular cysteine proteases, that include ubiquitously expressed μ- and m-calpains. Both are heterodimers consisting of a distinct large catalytic subunit (calpain 1 for μ-calpain and calpain 2 for m-calpain) and a common regulatory subunit, calpain 4. The physiological roles of calpain remain unclear in the organs, including the heart, but it has been suggested that calpain is activated by Ca(2+) overload in diseased hearts resulting in cardiac dysfunction. In the present study, cardiac-specific calpain 4-deficient mice were generated to elucidate the role of calpain in the heart in response to hemodynamic stress. Cardiac-specific deletion of calpain 4 resulted in decreased protein levels of calpain 1 and 2 and showed no cardiac phenotypes under baseline conditions, but caused left ventricle dilatation, contractile dysfunction and heart failure with interstitial fibrosis 1 week after pressure overload. Pressure-overloaded calpain 4-deficient hearts took up a membrane-impermeant dye, Evans blue, indicating plasma membrane disruption. Membrane repair assays using a two-photon laser-scanning microscope revealed that calpain 4-deficient cardiomyocytes failed to reseal a plasma membrane that had been disrupted by laser irradiation. Thus, the data from the present study indicate that calpain protects the heart from hemodynamic stresses, such as pressure overload.
Authors:
Manabu Taneike; Isamu Mizote; Takashi Morita; Tetsuya Watanabe; Shungo Hikoso; Osamu Yamaguchi; Toshihiro Takeda; Takafumi Oka; Takahito Tamai; Jota Oyabu; Tomokazu Murakawa; Hiroyuki Nakayama; Kazuhiko Nishida; Junji Takeda; Naoki Mochizuki; Issei Komuro; Kinya Otsu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-27
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  -     ISSN:  1083-351X     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Osaka University Graduate School of Medicine, Japan;
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