Nuclear Translocation of Calpain-2 Mediates Apoptosis of Hypertrophied Cardiomyocytes in Transverse Aortic Constriction Rat

被引：16
作者：
Sheng, Juan-Juan [1 ]
Chang, Hui [1 ]
Yu, Zhi-Bin [1 ]
机构：
[1] Fourth Mil Med Univ, Dept Aerosp Physiol, Xian 710032, Peoples R China
来源：
JOURNAL OF CELLULAR PHYSIOLOGY | 2015年 / 230卷 / 11期
基金：
中国国家自然科学基金;
关键词：
INDUCED CARDIAC-HYPERTROPHY; ANGIOTENSIN-II; HEART-FAILURE; MU-CALPAIN; KAPPA-B; DELTA-B; ACTIVATION; PATHWAY; PHOSPHORYLATION; HYPERTENSION;
D O I：
10.1002/jcp.24999
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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 Ca2+ activated calpain-2 in hypertrophied cardiomyocytes. Ang II enhanced the interaction between activated calpain-2 and Ca2+/calmodulin-dependent protein kinase II B (CaMKIIB), and promoted the degradation of CaMKIIB by calpain-2 in the nuclei of hypertrophied cardiomyocytes. Consequently, the depressed CaMKIIB 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 CaMKIIB pathway. J. Cell. Physiol. 9999: 2743-2754, 2015. (c) 2015 Wiley Periodicals, Inc.
引用
收藏
页码：2743 / 2754
页数：12
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