Mitochondria to nucleus translocation of AIF in mice lacking Hsp70 during ischemia/reperfusion
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Sangita Choudhury Soochan Bae Qingen Ke Ji Yoo Lee Jacob Kim Peter M. Kang
- چاپ و سال / کشور: 2011
Description
Heat shock protein 70 (Hsp70) has been shown to have an anti-apoptotic function, but its mechanism is not clear in heart. In this study, we examined the effect of Hsp70 deletion on AIF-induced apoptosis during ischemia/ reperfusion (I/R) in vivo. Although Hsp70 KO and WT mice demonstrated similar amounts of AIF released from mitochondria after I/R surgery, Hsp70 KO mice showed a significantly greater increase in apoptosis, larger infarct size, and decreased cardiac output. There was also a significant fourfold increase in the nuclear accumulation of AIF in Hsp70 KO mice compared with WT mice. Treatment with 4-AN (4-amino-1,8-napthalimide, 3 mg/kg), a potent inhibitor of PARP-1, which is a critical regulator of AIF-induced apoptosis, significantly blocked the release of AIF from mitochondria and the translocation of AIF into the nuclei after I/R in both WT and Hsp70 KO mice. In addition, 4-AN treatment resulted in a significant inhibition of apoptosis, a reduction of infarct size, and attenuated cardiac dysfunction in both WT and Hsp70 KO mice after I/R. The anti-apoptotic function of Hsp70 occurs through the inhibition of AIF-induced apoptosis by blocking the mitochondria to nucleus translocation of AIF. PARP-1 inhibition improves cardiac function by blocking AIFinduced apoptosis
Basic Res Cardiol (2011) 106:397–407 Received: 29 July 2010 / Revised: 2 February 2011 / Accepted: 21 February 2011 / Published online: 9 March 2011
