NADPH Oxidase-1 Plays a Key Role in Keratinocyte Responses to UV Radiation and UVB-Induced Skin Carcinogenesis

• Published in: Journal of investigative dermatology Vol. 137; no. 6; pp. 1311 - 1321
• Main Authors: Raad, Houssam, Serrano-Sanchez, Martin, Harfouche, Ghida, Mahfouf, Walid, Bortolotto, Doriane, Bergeron, Vanessa, Kasraian, Zeinab, Dousset, Lea, Hosseini, Mohsen, Taieb, Alain, Rezvani, Hamid Reza
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2017
• Subjects: Animals; Apoptosis - genetics; Apoptosis - radiation effects; Carcinogenesis - radiation effects; Cells, Cultured; Disease Models, Animal; Female; Keratinocytes - cytology; Keratinocytes - radiation effects; Mice; Mice, Hairless; Mice, Transgenic; Molecular Targeted Therapy; NADH, NADPH Oxidoreductases - genetics; NADH, NADPH Oxidoreductases - radiation effects; NADPH Oxidase 1; NADPH Oxidases - drug effects; NADPH Oxidases - metabolism; Neoplasms, Radiation-Induced - physiopathology; Neoplasms, Radiation-Induced - prevention & control; Pyrazoles - pharmacology; Pyrazolones; Pyridines - pharmacology; Pyridones; Random Allocation; Risk Factors; Skin Neoplasms - etiology; Skin Neoplasms - physiopathology; Ultraviolet Rays - adverse effects; NADPH; SCC; DDR; sh; CPD; NOX; InhNOX1; ROS; NER; XPC
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1016/j.jid.2016.12.027

The nicotinamide adenine dinucleotide phosphate oxidase (NOX) family enzymes are involved in several physiological functions. However, their roles in keratinocyte responses to UV radiation have not been clearly elucidated. This study shows that, among other NOX family members, UVB irradiation results in a biphasic activation of NOX1 that plays a critical role in defining keratinocyte fate through the modulation of the DNA damage response network. Indeed, suppression of both bursts of UVB-induced NOX1 activation by using a specific peptide inhibitor of NOX1 (InhNOX1) is associated with increased nucleotide excision repair efficiency and reduction of apoptosis, which is finally translated into decreased photocarcinogenesis. On the contrary, when only the second peak of UVB-induced NOX1 activation is blocked, both nucleotide excision repair efficiency and apoptosis are decreased. Our results show that inhibition of NOX1 activation could be a promising target for the prevention and treatment of UVB-induced skin cancer in nucleotide excision repair-proficient and -deficient patients.