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

Citation
Sj. Lee et al., Role of inducible heat shock protein 70 in radiation-induced cell death, CELL STR CH, 6(3), 2001, pp. 273-281
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL STRESS & CHAPERONES
ISSN journal
1355-8145 → ACNP
Volume
6
Issue
3
Year of publication
2001
Pages
273 - 281
Database
ISI
SICI code
1355-8145(200107)6:3<273:ROIHSP>2.0.ZU;2-O
Abstract
We previously demonstrated the protective effect of inducible heat shock pr otein 70 (Hsp70) against gamma radiation. Herein, we extend our studies on the possible role of Hsp70 to ionizing radiation-induced cell cycle regulat ion. The growth rate of inducible hsp70-transfected cells was 2-3 hours slo wer than that of control cells. Flow cytometric analysis of cells at GI pha se synchronized by serum starvation also showed the growth delay in the Hsp 70-over-expressing cells. In addition, reduced cyclin D1 and Cdc2 levels an d increased dephosphorylated phosphoretinoblastoma (pRb) were observed in i nducible hsp70-transfected cells, which were probably responsible for the r eduction of cell growth. To find out if inducible Hsp70-mediated growth del ay affected radiation-induced cell cycle regulation, flow cytometric and mo lecular analyses of cell cycle regulatory proteins and their kinase were pe rformed. The radiation-induced G2/M arrest was found to be inhibited by Hsp 70 overexpression and reduced p21(Waf) induction and its kinase activity by radiation in the Hsp70-transfected cells. In addition, radiation-induced c yclin A or B1 expressions together with their kinase activities were also i nhibited by inducible Hsp70, which represented reduced mitotic cell death. Indeed, hsp70 transfectants showed less induction of radiation-induced apop tosis. When treated with nocodazole, radiation-induced mitotic arrest was i nhibited by inducible Hsp70. These results strongly suggested that inducibl e Hsp70 modified growth delay (increased G1 phase) and reduced G2/M phase a rrest, subsequently resulting in inhibition of radiation-induced cell death .