| Calpain protects the heart from hemodynamic stress. | |
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MedLine Citation:
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PMID: 21795695 Owner: NLM Status: Publisher |
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 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. |
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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 Date: 2011-7-27 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Osaka University Graduate School of Medicine, Japan; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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