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

• DOI: 10.1038/jid.2014.511
• Publication Date: 2014-12-01T14:45:18Z
• Authors: Mohsen Hosseini; Walid Mahfouf; Martin Serrano-Sa...; Houssam Raad; Ghida Harfouche; Marc Bonneu; Stephane Claverol; Frederic Mazurier; Rodrigue Rossignol; Alain Taieb; Hamid Reza Rezvani
• Keywords: Keratinocytes; Light; Dermatology; Biochemistry; Mice; 03 medical and health sciences; Animals; Humans; NADH, NADPH Oxidoreductases; Protein Precursors; Molecular Biology; Cyclin-Dependent Kinase Inhibitor p16; Adaptor Proteins, Signal Transducing; Mice, Knockout; Xeroderma Pigmentosum; 0303 health sciences; Nuclear Proteins; Proteins; Cell Biology; Lamin Type A; Mitochondria; Skin Aging; 3. Good health; DNA-Binding Proteins; Oxidative Stress; NADPH Oxidase 1; Reactive Oxygen Species

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 p16(INK4a) 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.