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KPC1 alleviates hypoxia/reoxygenation-induced apoptosis in rat cardiomyocyte cells though BAX degradation |
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| Authors: | Ye Yuan Yong-yi Wang Xin Liu Bin Luo Lei Zhang Fei Zheng Xing-Yuan Li Ling-Yun Guo Lu Wang Miao Jiang Ya-mu Pan Yu-wen Yan Jian-ye Yang Shi-You Chen Jia-Ning Wang Jun-Ming Tang |
| Institution: | 1. Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China;2. Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Ye Yuan and Yong-yi Wang contributed equally to this study.;3. Laboratory Animal Center, Hubei, China;4. Department of Physiology, School of Basic Medicine Science, Hubei University of Medicine, Hubei, China;5. Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China Institute of Biomedicine and Key Lab of Human Embryonic Stem Cell of Hubei Province, Hubei University of Medicine, Hubei, China;6. Department of Physiology & Pharmacology, The University of Georgia, Athens, USA |
| Abstract: | Bax triggers cell apoptosis by permeabilizing the outer mitochondrial membrane, leading to membrane potential loss and cytochrome c release. However, it is unclear if proteasomal degradation of Bax is involved in the apoptotic process, especially in heart ischemia-reperfusion (I/R)-induced injury. In the present study, KPC1 expression was heightened in left ventricular cardiomyocytes of patients with coronary heart disease (CHD), in I/R-myocardium in vivo and in hypoxia and reoxygenation (H/R)-induced cardiomyocytes in vitro. Overexpression of KPC1 reduced infarction size and cell apoptosis in I/R rat hearts. Similarly, the forced expression of KPC1 restored mitochondrial membrane potential (MMP) and cytochrome c release driven by H/R in H9c2 cells, whereas reducing cell apoptosis, and knockdown of KPC1 by short-hairpin RNA (shRNA) deteriorated cell apoptosis induced by H/R. Mechanistically, forced expression of KPC1 promoted Bax protein degradation, which was abolished by proteasome inhibitor MG132, suggesting that KPC1 promoted proteasomal degradation of Bax. Furthermore, KPC1 prevented basal and apoptotic stress-induced Bax translocation to mitochondria. Bax can be a novel target for the antiapoptotic effects of KPC1 on I/R-induced cardiomyocyte apoptosis and render mechanistic penetration into at least a subset of the mitochondrial effects of KPC1. |
| Keywords: | apoptosis Bax cardiomyocyte KPC1 mitochondrial function |