期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 286, 期 37, 页码 32170-32177出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111.248088
关键词
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资金
- Ministry of Education, Culture, Sports, Science, and Technology
- Grants-in-Aid for Scientific Research [21390240] Funding Source: KAKEN
Calpains make up a family of Ca2+-dependent intracellular cysteine proteases that include ubiquitously expressed mu- and m-calpains. Both are heterodimers consisting of a distinct large catalytic subunit (calpain 1 for mu-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 Ca2+ 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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