Induction of replicative senescence biomarkers by sublethal oxidative stresses in normal human fibroblast

被引:295
作者
Dumont, P
Burton, M
Chen, QM
Gonos, ES
Frippiat, C
Mazarati, JB
Eliaers, F
Remacle, J
Toussaint, O
机构
[1] Univ Namur FUNDP, Lab Cellular Biochem & Biol, Dept Biol, B-5000 Namur, Belgium
[2] Univ Arizona, Dept Pharmacol & Toxicol, Tucson, AZ USA
[3] Natl Hellen Res Fdn, Inst Biol Res & Biotechnol, Athens, Greece
关键词
aging; cell cycle; fibroblast; gene expression; free radicals; hydrogen peroxide; oxidative stress; replicative senescence; tert-butylhydroperoxide;
D O I
10.1016/S0891-5849(99)00249-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We tested the long-term effects of sublethal oxidative stresses on replicative senescence. WI-38 human diploid fibroblasts (HDFs) at early cumulative population doublings (CPDs) were exposed to five stresses with 30 mu M tert-butylhydroperoxide (t-BHP). After at least 2 d of recovery, the cells developed biomarkers of replicative senescence: loss of replicative potential, increase in senescence-associated beta-galactosidase activity, overexpression of p21(Waf-1/SDI-1/Cip1) , and inability to hyperphosphorylate pRb. The level of mRNAs overexpressed in senescent WI-38 or IMR-90 HDFs increased after five stresses with 30 mu M t-BHP or a single stress under 450 mu M H2O2. These corresponding genes include fibronectin, osteonectin, alpha 1(I)-procollagen, apolipoprotein J, SM22, SS9, and GTP-alpha binding protein. The common 4977 bp mitochondrial DNA deletion was detected in WI-38 HDFs at late CPDs and at early CPDs after t-BHP stresses. In conclusion, sublethal oxidative stresses lead HDFs to a state close to replicative senescence. (C) 2000 Elsevier Science Inc.
引用
收藏
页码:361 / 373
页数:13
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