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

Patrick Dumont, Maggi Burton, Qin Chen, Efstathios S. Gonos, Christophe Frippiat, Jean Baptiste Mazarati, François Eliaers, José Remacle, Olivier Toussaint

Research output: Contribution to journalArticle

285 Scopus citations

Abstract

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 μM 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 β-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 μM t-BHP or a single stress under 450 μM H2O2. These corresponding genes include fibronectin, osteonectin, α1(I)-procollagen, apolipoprotein J, SM22, SS9, and GTP-α 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. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)361-373
Number of pages13
JournalFree Radical Biology and Medicine
Volume28
Issue number3
DOIs
Publication statusPublished - Feb 1 2000

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Keywords

  • Aging
  • Cell cycle
  • Fibroblast
  • Free radicals
  • Gene expression
  • Hydrogen peroxide
  • Oxidative stress
  • Replicative senescence
  • tert-butylhydroperoxide

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

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