title: Nuclear Translocation of Calpain-2 Mediates Apoptosis of Hypertrophied Cardiomyocytes in Transverse Aortic Constriction Rat.
abstract: Apoptosis of cardiomyocytes plays an important role in the transition from cardiac hypertrophy to heart failure. Hypertrophied cardiomyocytes show enhanced susceptibility to apoptosis. Therefore, the aim of this study was to determine the susceptibility to apoptosis and its mechanism in hypertrophied cardiomyocytes using a rat model of transverse abdominal aortic constriction (TAC). Sixteen weeks of TAC showed compensatory and pathological hypertrophy in the left ventricle. TUNEL-positive nuclei were significantly increased in TAC with angiotensin II (Ang II) treatment. Calpain inhibitor, PD150606, effectively inhibited Ang II-induced apoptosis of hypertrophied cardiomyocytes. Ang II increased nuclear translocation of intracellular Ca(2+) activated calpain-2 in hypertrophied cardiomyocytes. Ang II enhanced the interaction between activated calpain-2 and Ca(2+)/calmodulin-dependent protein kinase II δB (CaMKIIδB), and promoted the degradation of CaMKIIδB by calpain-2 in the nuclei of hypertrophied cardiomyocytes. Consequently, the depressed CaMKIIδB downregulated the expression of antiapoptotic Bcl-2 leading to mitochondrial depolarization and release of cytochrome c led to apoptosis of hypertrophied cardiomyocytes. In conclusion, hypertrophied cardiomyocytes show increased susceptibility to apoptosis during Ang II stimulation via nuclear calpain-2 and CaMKIIδB pathway.
authors.affiliation: Department of Aerospace Physiology, Fourth Military Medical University, 169# Changlexi Road, Xi'an, China.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Sheng
authors.affiliation: Department of Aerospace Physiology, Fourth Military Medical University, 169# Changlexi Road, Xi'an, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chang
authors.affiliation: Department of Aerospace Physiology, Fourth Military Medical University, 169# Changlexi Road, Xi'an, China.
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Yu
mesh_terms: D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D003251:Constriction, Pathologic / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D015398:Signal Transduction
chemical_list: D000804:Angiotensin II; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002154:Calpain