Bcl-2 protects against oxidative stress while inducing premature senescence.
Replicative senescence is a cellular response to stress that has been postulated to serve as a tumor suppression mechanism and a contributor to aging. Numerous experimental studies have demonstrated that an apparently identical senescent state can also be prematurely induced in vitro in different cell types following sublethal oxidative stress stimuli. The former suggests a molecular link between cell cycle regulation and cell survival that could involve regulatory proteins such as Bcl-2. There is strong evidence that, in addition to its well-known effects on apoptosis, Bcl-2 is involved in antioxidant protection and regulation of cell cycle progression. The aim of this work was to determine if the protection against oxidative stress mediated by Bcl-2 could prevent or delay oxidative stress-induced senescence. Using a retroviral infection system, Bcl-2 was overexpressed in primary, nonembryonic mice fibroblasts obtained from lungs derived from 2-month-old CD1 mice. Fibroblasts overexpressing Bcl-2 were exposed to 75 microM H2O2 for 2 h to induce SIPS. The rate of proliferation and the increment of senescent cells were then determined. Our results indicate that overexpression of Bcl-2 protected primary fibroblasts against oxidative stress-mediated reduction in cell proliferation, but did not prevent premature senescence.
Departamento Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Iztapalapa. A.P. 55-535, C.P 09340, México D.F., México.
Norma E
NE
López-Diazguerrero
Hugo
H
López-Araiza
Juan C
JC
Conde-Perezprina
Leticia
L
Bucio
María C
MC
Cárdenas-Aguayo
José L
JL
Ventura
Luis
L
Covarrubias
María C
MC
Gutiérrez-Ruíz
Alejandro
A
Zentella
Mina
M
Königsberg
D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide