| Calpain protects the heart from hemodynamic stress. | |
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MedLine Citation:
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PMID: 21795695 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-07-27 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-12 Completed Date: 2011-11-22 Revised Date: 2012-09-28 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 32170-7 Citation Subset: IM |
Affiliation:
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Departments of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure* Calcium / metabolism Calpain / genetics, metabolism* Cell Membrane / enzymology, genetics, pathology Heart Failure / enzymology*, genetics, physiopathology Mice Mice, Knockout Muscle Proteins / genetics, metabolism* Myocardial Contraction* Myocardium / enzymology*, pathology Stress, Physiological |
| Chemical | |
Reg. No./Substance:
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0/Muscle Proteins; 7440-70-2/Calcium; EC 3.4.22.-/Calpain |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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