Protection of normal human reconstructed epidermis from UV by catalase overexpression.
Reactive oxygen species (ROS) generated by ultraviolet (UV) irradiation are counterbalanced by endogenous antioxidant systems. To test the hypothesis of a novel photoprotective approach, we irradiated epidermis reconstructed with normal human keratinocytes overexpressing sustainably lentivirus-mediated catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD) or manganese superoxide dismutase (MnSOD) enzymes. We found that following UVB irradiation there was a marked decrease in sunburn cell formation, caspase-3 activation and p53 accumulation in human reconstructed epidermis overexpressing CAT. Moreover, UVA-induced hypertrophy and DNA oxidation (8-oxodeoxyguanosine) were decreased by CAT overexpression. These effects were not achieved by overexpression of CuZnSOD or MnSOD. In conclusion, vector-mediated CAT overexpression could be a promising photoprotective tool against deleterious effects of UV irradiation such skin cancer especially in monogenic/polygenic photosensitive disorders characterized by ROS accumulation.
Rezvani
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INSERM E 0217, University Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux cedex, France.
Cario-André
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Pain
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Ged
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deVerneuil
H
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Taïeb
A
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D017209:Apoptosis; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D004817:Epidermis / Q000201:enzymology / Q000528:radiation effects*; D006801:Humans; D007150:Immunohistochemistry; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D019076:Transgenes; D014466:Ultraviolet Rays
D002374:Catalase; D013482:Superoxide Dismutase