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 inhibit H(2)O(2)-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 H(2)O(2) treatment, and in these cells nucleolin/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 H(2)O(2)-induced apoptosis. When nucleolin/C23 was knocked down with an antisense oligomer, H(2)O(2)-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 stress-induced apoptosis.
Jiang
Bimei
B
Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Zhang
Bin
B
Liang
Pengfei
P
Song
Juan
J
Deng
Hongbing
H
Tu
Zizhi
Z
Deng
Gonghua
G
Xiao
Xianzhong
X
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010750:Phosphoproteins / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D000097796:Nucleolin
D018840:HSP70 Heat-Shock Proteins; D006861:Hydrogen Peroxide; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016601:RNA-Binding Proteins; D000097796:Nucleolin