Document Detail

Calpain protects the heart from hemodynamic stress.
MedLine Citation:
PMID:  21795695     Owner:  NLM     Status:  MEDLINE    
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 this 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 calpains 1 and 2 and showed no cardiac phenotypes under base-line 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 indicate that calpain protects the heart from hemodynamic stresses, such as pressure overload.
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; Research Support, Non-U.S. Gov't     Date:  2011-07-27
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-12     Completed Date:  2011-11-22     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32170-7     Citation Subset:  IM    
Departments of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, USA.
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MeSH Terms
Blood Pressure*
Calcium / metabolism
Calpain / genetics,  metabolism*
Cell Membrane / enzymology,  genetics,  pathology
Heart Failure / enzymology*,  genetics,  physiopathology
Mice, Knockout
Muscle Proteins / genetics,  metabolism*
Myocardial Contraction*
Myocardium / enzymology*,  pathology
Stress, Physiological
Reg. No./Substance:
0/Muscle Proteins; 7440-70-2/Calcium; EC 3.4.22.-/Calpain

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