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J Invest Dermatol. 2015 Apr;135(4):1108-1118. doi: 10.1038/jid.2014.511. Epub 2014 Dec 1.

Premature skin aging features rescued by inhibition of NADPH oxidase activity in XPC-deficient mice.

Author information

1
Inserm U1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France.
2
Centre Génomique Fonctionnelle de Bordeaux, Université de Bordeaux, Bordeaux, France.
3
Inserm U1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France; Centre de Référence pour les Maladies Rares de la Peau, CHU de Bordeaux, France.
4
Inserm U1035, Bordeaux, France; Université de Bordeaux, Maladies Rares: Génétique et Métabolisme (MRGM), Bordeaux, France.
5
Inserm U1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France; Centre de Référence pour les Maladies Rares de la Peau, CHU de Bordeaux, France; Département de Dermatologie and Dermatologie Pédiatrique, CHU de Bordeaux, France.
6
Inserm U1035, Bordeaux, France; Université de Bordeaux, Bordeaux, France; Centre de Référence pour les Maladies Rares de la Peau, CHU de Bordeaux, France. Electronic address: hamid-reza.rezvani@u-bordeaux.fr.

Abstract

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.

PMID:
25437426
DOI:
10.1038/jid.2014.511
[Indexed for MEDLINE]
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