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Role of inducible heat shock protein 70 in radiation-induced cell death

 Su-Jae Lee  ;  Sun-Ah Choi  ;  Kang-Hyun Lee  ;  Hee-Yong Chung  ;  Tae-Hwan Kim  ;  Chul-Koo Cho  ;  Yun-Sil Lee 
 Cell Stress & Chaperones, Vol.6(3) : 273-281, 2001 
Journal Title
 Cell Stress & Chaperones 
Issue Date
We previously demonstrated the protective effect of inducible heat shock protein 70 (Hsp70) against gamma radiation. Herein, we extend our studies on the possible role of Hsp70 to ionizing radiation-induced cell cycle regulation. The growth rate of inducible hsp70-transfected cells was 2–3 hours slower than that of control cells. Flow cytometric analysis of cells at G1 phase synchronized by serum starvation also showed the growth delay in the Hsp70-overexpressing cells. In addition, reduced cyclin D1 and Cdc2 levels and increased dephosphorylated phosphoretinoblastoma (pRb) were observed in inducible hsp70-transfected cells, which were probably responsible for the reduction of cell growth. To find out if inducible Hsp70-mediated growth delay affected radiation-induced cell cycle regulation, flow cytometric and molecular analyses of cell cycle regulatory proteins and their kinase were performed. The radiation-induced G2/M arrest was found to be inhibited by Hsp70 overexpression and reduced p21Waf induction and its kinase activity by radiation in the Hsp70-transfected cells. In addition, radiation-induced cyclin A or B1 expressions together with their kinase activities were also inhibited by inducible Hsp70, which represented reduced mitotic cell death. Indeed, hsp70 transfectants showed less induction of radiation-induced apoptosis. When treated with nocodazole, radiation-induced mitotic arrest was inhibited by inducible Hsp70. These results strongly suggested that inducible Hsp70 modified growth delay (increased G1 phase) and reduced G2/M phase arrest, subsequently resulting in inhibition of radiation-induced cell death.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실)
Yonsei Authors
이윤실(Lee, Yun Sil)
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