TY - JOUR
T1 - Induction of replicative senescence biomarkers by sublethal oxidative stresses in normal human fibroblast
AU - Dumont, Patrick
AU - Burton, Maggi
AU - Chen, Qin M.
AU - Gonos, Efstathios S.
AU - Frippiat, Christophe
AU - Mazarati, Jean Baptiste
AU - Eliaers, François
AU - Remacle, José
AU - Toussaint, Olivier
PY - 2000/2/1
Y1 - 2000/2/1
N2 - 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.
AB - 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.
KW - Aging
KW - Cell cycle
KW - Fibroblast
KW - Free radicals
KW - Gene expression
KW - Hydrogen peroxide
KW - Oxidative stress
KW - Replicative senescence
KW - tert-butylhydroperoxide
UR - https://www.scopus.com/pages/publications/0033963144
UR - https://www.scopus.com/pages/publications/0033963144#tab=citedBy
U2 - 10.1016/S0891-5849(99)00249-X
DO - 10.1016/S0891-5849(99)00249-X
M3 - Article
C2 - 10699747
AN - SCOPUS:0033963144
SN - 0891-5849
VL - 28
SP - 361
EP - 373
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 3
ER -