Original Article
Cancer Gene Therapy (2007) 14, 174–186. doi:10.1038/sj.cgt.7701000; published online 20 October 2006
Protection of normal human reconstructed epidermis from UV by catalase overexpression
H R Rezvani1, M Cario-André1, C Pain1, C Ged1, H deVerneuil1 and A Taïeb1,2
- 1Inserm E 0217, University Victor Segalen Bordeaux 2, Bordeaux, France
- 2CHU Bordeaux, Department of Dermatology, Hôpital St André, Bordeaux, France
Correspondence: Professor A Taïeb, Inserm E 0217, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. E-mail: alain.taieb@chu-bordeaux.fr
Received 1 May 2006; Revised 13 June 2006; Accepted 19 August 2006; Published online 20 October 2006.
Abstract
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.
Keywords:
gene transfer, superoxide dismutase, photoprotection, lentiviral vector
Abbreviations:
CAT, catalase; CPD, cyclobutane pyrimidine dimer; CuZnSOD, copper/zinc superoxide dismutase; E, epidermis; MnSOD, manganese superoxide dismutase; NT, non-transduced; nIr, non-irradiated; ODC, ornithine decarboxylase; 8-oxodG, 8-oxodeoxyguanosine; RE, reconstructed epidermis; SBC, sunburn cell; SVHK, SV40-transformed human keratinocytes
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