Overexpression of MsrA protects WI-38 SV40 human fibroblasts against H2O2-mediated oxidative stress.
Proteins are modified by reactive oxygen species, and oxidation of specific amino acid residues can impair their biological functions, leading to an alteration in cellular homeostasis. Oxidized proteins can be eliminated through either degradation or repair. Repair is limited to the reversion of a few modifications such as the reduction of methionine oxidation by the methionine sulfoxide reductase (Msr) system. However, accumulation of oxidized proteins occurs during aging, replicative senescence, or neurological disorders or after an oxidative stress, while Msr activity is impaired. In order to more precisely analyze the relationship between oxidative stress, protein oxidative damage, and MsrA, we stably overexpressed MsrA full-length cDNA in SV40 T antigen-immortalized WI-38 human fibroblasts. We report here that MsrA-overexpressing cells are more resistant than control cells to hydrogen peroxide-induced oxidative stress, but not to ultraviolet A irradiation. This MsrA-mediated resistance is accompanied by a decrease in intracellular reactive oxygen species and is partially abolished when cells are cultivated at suboptimal concentration of methionine. These results indicate that MsrA may play an important role in cellular defenses against oxidative stress, by catalytic removal of oxidant through the reduction of methionine sulfoxide, and in protection against death by limiting, at least in part, the accumulation of oxidative damage to proteins.
Picot
Cédric R
CR
Laboratoire de Biologie et Biochimie Cellulaire du Vieillissement, Université Paris 7-Denis Diderot, 2 Place Jussieu, Tower 33-23, First Floor, CC 7128, 75251 Paris Cedex 05, France.
Petropoulos
Isabelle
I
Perichon
Martine
M
Moreau
Marielle
M
Nizard
Carine
C
Friguet
Bertrand
B
D000375:Aging; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015151:Immunoblotting; D008715:Methionine / Q000031:analogs & derivatives / Q000737:chemistry; D051150:Methionine Sulfoxide Reductases; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000737:chemistry / Q000502:physiology*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry; D017382:Reactive Oxygen Species; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D018076:DNA, Complementary; D005609:Free Radicals; D011506:Proteins; D017382:Reactive Oxygen Species; D008715:Methionine; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D010100:Oxygen; C013111:methionine sulfoxide