| First Author | Taneike M | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 37 | Pages | 32170-7 |
| PubMed ID | 21795695 | Mgi Jnum | J:176736 |
| Mgi Id | MGI:5292591 | Doi | 10.1074/jbc.M111.248088 |
| Citation | Taneike M, et al. (2011) Calpain protects the heart from hemodynamic stress. J Biol Chem 286(37):32170-7 |
| abstractText | Calpains make up a family of Ca(2+)-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 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. |
