Calpain Protects the Heart from Hemodynamic Stress

• DOI: 10.1074/jbc.m111.248088
• Publication Date: 2011-07-28T04:21:48Z
• 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
• Keywords: Heart Failure; Mice, Knockout; 0301 basic medicine; Calpain; Myocardium; Cell Membrane; 610; Muscle Proteins; Blood Pressure; 540; Myocardial Contraction; 3. Good health; Mice; 03 medical and health sciences; Stress, Physiological; Animals; Calcium

Calpains make up a family of Ca(2+)-dependent intracellular cysteine proteases that include ubiquitously expressed μ- and m-calpains. Both are heterodimers consisting distinct large catalytic subunit (calpain 1 for μ-calpain calpain 2 m-calpain) common regulatory 4). The physiological roles remain unclear in the organs, including heart, but it has been suggested is activated by Ca(2+) overload diseased hearts, resulting cardiac dysfunction. In this study, cardiac-specific 4-deficient mice were generated to elucidate role heart response hemodynamic stress. Cardiac-specific deletion 4 resulted decreased protein levels calpains showed no phenotypes under base-line conditions caused left ventricle dilatation, contractile dysfunction, failure with interstitial fibrosis week after pressure overload. Pressure-overloaded hearts took membrane-impermeant dye, Evans blue, indicating plasma membrane disruption. Membrane repair assays using two-photon laser-scanning microscope revealed cardiomyocytes failed reseal had disrupted laser irradiation. Thus, data indicate protects from stresses, such as