title: NADPH Oxidase-1 Plays a Key Role in Keratinocyte Responses to UV Radiation and UVB-Induced Skin Carcinogenesis.
abstract: 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.
authors.affiliation: Inserm Unit 1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France.
authors.forename: Houssam
authors.initials: H
authors.lastname: Raad
authors.affiliation: Inserm Unit 1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Serrano-Sanchez
authors.affiliation: Inserm Unit 1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France.
authors.forename: Ghida
authors.initials: G
authors.lastname: Harfouche
authors.affiliation: Inserm Unit 1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France.
authors.forename: Walid
authors.initials: W
authors.lastname: Mahfouf
authors.affiliation: Inserm Unit 1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France.
authors.forename: Doriane
authors.initials: D
authors.lastname: Bortolotto
authors.affiliation: Inserm Unit 1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bergeron
authors.affiliation: Inserm Unit 1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Kasraian
authors.affiliation: Inserm Unit 1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France; Service de Dermatologie Adulte et Pédiatrique, Centre Hospitalier Universitaire de Bordeaux, France.
authors.forename: Lea
authors.initials: L
authors.lastname: Dousset
authors.affiliation: Inserm Unit 1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Hosseini
authors.affiliation: Inserm Unit 1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France; Service de Dermatologie Adulte et Pédiatrique, Centre Hospitalier Universitaire de Bordeaux, France; Centre de Référence pour les Maladies Rares de la Peau, Centre Hospitalier Universitaire de Bordeaux, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Taieb
authors.affiliation: Inserm Unit 1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France; Centre de Référence pour les Maladies Rares de la Peau, Centre Hospitalier Universitaire de Bordeaux, France. Electronic address: hamid-reza.rezvani@u-bordeaux.fr.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Rezvani
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D063646:Carcinogenesis / Q000528:radiation effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D015603:Keratinocytes / Q000166:cytology / Q000528:radiation effects*; D051379:Mice; D008812:Mice, Hairless; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics* / Q000528:radiation effects*; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000187:drug effects* / Q000378:metabolism; D009381:Neoplasms, Radiation-Induced / Q000503:physiopathology / Q000517:prevention & control; D011720:Pyrazoles / Q000494:pharmacology; D047069:Pyrazolones; D011725:Pyridines / Q000494:pharmacology; D011728:Pyridones; D011897:Random Allocation; D012307:Risk Factors; D012878:Skin Neoplasms / Q000209:etiology / Q000503:physiopathology; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D011720:Pyrazoles; D047069:Pyrazolones; D011725:Pyridines; D011728:Pyridones; C576694:setanaxib; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; C000614711:NOX1 protein, mouse