Premature Skin Aging Features Rescued by Inhibition of NADPH Oxidase Activity in XPC-Deficient Mice

• Published in: Journal of investigative dermatology Vol. 135; no. 4; pp. 1108 - 1118
• Main Authors: Hosseini, Mohsen, Mahfouf, Walid, Serrano-Sanchez, Martin, Raad, Houssam, Harfouche, Ghida, Bonneu, Marc, Claverol, Stephane, Mazurier, Frederic, Rossignol, Rodrigue, Taieb, Alain, Rezvani, Hamid Reza
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2015; Elsevier Limited
• Subjects: Animals; beta-Galactosidase - metabolism; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; DNA-Binding Proteins - genetics; Humans; Keratinocytes - cytology; Lamin Type A; Light; Mice; Mice, Knockout; Mitochondria - metabolism; NADH, NADPH Oxidoreductases - antagonists & inhibitors; NADH, NADPH Oxidoreductases - metabolism; NADPH Oxidase 1; Nuclear Proteins - metabolism; Oxidative Stress; Protein Precursors - metabolism; Proteins - genetics; Reactive Oxygen Species - metabolism; Skin Aging; Xeroderma Pigmentosum - metabolism
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2014.511

Xeroderma pigmentosum type C (XP-C) is characterized mostly by a predisposition to skin cancers and accelerated photoaging, but little is known about premature skin aging in this disease. By comparing young and old mice, we found that the level of progerin and p16INK4a expression, β-galactosidase activity, and reactive oxygen species, which increase with age, were higher in young Xpc-/- mice than in young Xpc+/+ ones. The expression level of mitochondrial complexes and mitochondrial functions in the skin of young Xpc-/- was as low as in control aged Xpc+/+animals. Furthermore, the metabolic profile in young Xpc-/- mice resembled that found in aged Xpc+/+ mice. Furthermore, premature skin aging features in young Xpc-/- mice were mostly rescued by inhibition of nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) activity by using a NOX1 peptide inhibitor, suggesting that the continuous oxidative stress due to overactivation of NOX1 has a causative role in the underlying pathophysiology.