tailieunhanh - Báo cáo khoa học: Nucleolin/C23 mediates the antiapoptotic effect of heat shock protein 70 during oxidative stress

Although heat shock protein 70 (Hsp70) has been shown to markedly inhi-bit H2O2-induced apoptosis in C2C12 cells, and nucleolin⁄C23 has also been implicated in apoptosis, the relationship of these two molecules is still largely unknown. The aim of the current study was to investigate the potential involvement of nucleolin⁄C23 in the antiapoptotic mechanism of Hsp70. | Nucleolin C23 mediates the antiapoptotic effect of heat shock protein 70 during oxidative stress Bimei Jiang1 Bin Zhang1 Pengfei Liang2 Juan Song1 Hongbing Deng1 Zizhi Tu1 Gonghua Deng1 and Xianzhong Xiao1 1 Department of Pathophysiology Xiangya Schoolof Medicine CentralSouth University Changsha Hunan China 2 Department of Burns and Plastic Surgery Xiangya Hospital CentralSouth University Changsha Hunan China Keywords apoptosis cardiomyocytes heat shock protein 70 hydrogen peroxide nucleolin C23 Correspondence Xianzhong Xiao Department of Pathophysiology Xiangya Schoolof Medicine CentralSouth University Changsha Hunan 410008 China Fax 86 731 82355019 Tel 86 731 2355019 E-mail xianzhongxiao@ Received 22 August 2009 revised 26 October 2009 accepted 23 November 2009 doi Although heat shock protein 70 Hsp70 has been shown to markedly inhibit H2O2-induced apoptosis in C2C12 cells and nucleolin C23 has also been implicated in apoptosis the relationship of these two molecules is still largely unknown. The aim of the current study was to investigate the potential involvement of nucleolin C23 in the antiapoptotic mechanism of Hsp70. We found that primary cultures of neonatal rat cardiomyocytes underwent apoptosis upon H2O2 treatment and in these cells nucleo-lin C23 protein was highly unstable and had a half-life of less than 4 h. However transfection with Hsp70 greatly stabilized nucleolin C23 and also protected the cells from H2O2-induced apoptosis. When nucleolin C23 was knocked down with an antisense oligomer H2O2-induced apoptosis became more severe even in Hsp70-overexpressed cells demonstrating an essential role of nucleolin C23 in the antiapoptotic effects of Hsp70. Similar results were obtained by both nuclear morphology observation and caspase-3 activity assay. Therefore these data provide evidence that nucleolin C23 is an essential downstream effecter of Hsp70 in the protection of cardiomyocytes against oxidative .