Protective effects of catalase overexpression on UVB-induced apoptosis in normal human keratinocytes.
UV-induced apoptosis in keratinocytes is a highly complex process in which various molecular pathways are involved. These include the extrinsic pathway via triggering of death receptors and the intrinsic pathway via DNA damage and reactive oxygen species (ROS) formation. In this study we investigated the effect of catalase and CuZn-superoxide dismutase (SOD) overexpression on apoptosis induced by UVB exposure at room temperature or 4 degrees C on normal human keratinocytes. Irradiation at low temperature reduced UV-induced apoptosis by 40% in normal keratinocytes independently of any change in p53 and with a decrease in caspase-8 activation. Catalase overexpression decreased apoptosis by 40% with a reduction of caspase-9 activation accompanied by a decrease in p53. Keeping cells at low temperature and catalase overexpression had additive effects. CuZn-SOD overexpression had no significant effect on UVB-induced apoptosis. UVB induced an increase in ROS levels at two distinct stages: immediately following irradiation and around 3 h after irradiation. Catalase overexpression inhibited only the late increase in ROS levels. We conclude that catalase overexpression has a protective role against UVB irradiation by preventing DNA damage mediated by the late ROS increase.
Rezvani
Hamid Reza
HR
INSERM E0217, University Victor Segalen Bordeaux 2, Bordeaux F-33000, France.
Mazurier
Frédéric
F
Cario-André
Muriel
M
Pain
Catherine
C
Ged
Cécile
C
Taïeb
Alain
A
de Verneuil
Hubert
H
D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D003080:Cold Temperature; D004249:DNA Damage / Q000502:physiology; D005786:Gene Expression Regulation / Q000528:radiation effects; D005822:Genetic Vectors; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology* / Q000528:radiation effects; D016086:Lentivirus / Q000235:genetics; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D012694:Serine; D002374:Catalase; D013482:Superoxide Dismutase; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases