Induction of replicative senescence biomarkers by sublethal oxidative stresses in normal human fibroblast.
Free Radic Biol Med
; 28(3): 361-73, 2000 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-10699747
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 microM 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 microM t-BHP or a single stress under 450 microM H(2)O(2). These corresponding genes include fibronectin, osteonectin, alpha1(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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
/
Senescência Celular
/
Estresse Oxidativo
/
Chaperonas Moleculares
/
Fibroblastos
Limite:
Humans
Idioma:
En
Revista:
Free Radic Biol Med
Ano de publicação:
2000
Tipo de documento:
Article