CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress–induced myocardial necroptosis (Nature Medicine 2016, 22(2):175-184)

報告日期: 2016/11/29
報告時間: 4:00/4:50
報告學生: 陳柏源
講評老師: 王育民
附件下載: 下載[1604-1473728464-1.pdf] 

CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress–induced myocardial necroptosis

 Ting Zhang, Yan Zhang, Mingyao Cui, Li Jin, Yimei Wang, Fengxiang Lv, Yuli Liu, Wen Zheng, Haibao Shang, Jun Zhang, Mao Zhang, Hongkun Wu, Jiaojiao Guo, Xiuqin Zhang, Xinli Hu, Chun-Mei Cao& Rui-Ping Xiao

Nature medicine, February 2016

Speaker: Po-yuan Chen(陳柏源)               Time: 16:00-16:50, 16/11/29

Commentator: Dr. Ju-Ming Wang

Abstract:

    Apoptosis and programmed necrosis (necroptosis) are involved in cardiac pathological conditions, such as ischemia-reperfusion-induced myocardial infarction and heart failure1. The underlining mechanisms of apoptosis-mediated cardiac pathology have been well-studied, however, signaling pathways involved in necroptosis-mediated cardiac pathology remain a lot unclear. In this study, the authors found that after myocardial injury, the upregulation of receptor-interacting protein3 (RIP3), but not the well-known cascades RIP1 and MLKL, would activate Ca2+-calmodulin-dependent-protein kinase (CaMKII), leading to necroptosis in myocardial cells. In mice, RIP3 knockout could relieve myocardial necroptosis, heart failure and heart remodeling induced by ischemia-reperfusion or doxorubicin treatment. Overexpression of CaMKII dominate negative protein also alleviated myocardial necroptosis. Moreover, the authors found that phosphorylated or oxidized CaMKII triggered mitochondrial permeability transition pore opening, resulting in the necroptosis of myocardial cells. In conclusion, this study revealed that RIP3-CaMKII-mPTP pathway can be activated under ischemia-reperfusion injury in heart, and this novel necroptosis pathway could provide a new therapeutic target for cardiac injury, heart failure or remodeling.

 

Reference:

  1. Wajihah Mughal, etal. Cell death signaling mechanism in heart failure. Exp Clin Cardiol. 2011 Winter; 16(4): 102–108.