title: Acceleration of UVB-induced photoageing in nrf2 gene-deficient mice.
abstract: Ultraviolet (UV) radiation is one of the most important environmental factors involved in the pathogenesis of premature skin ageing, termed photoageing. The harmful effects of UV in photoageing are associated with the generation of reactive oxygen species, and cellular antioxidants act to prevent the occurrence and reduce the severity of UV-induced photoageing. The transcription factor Nrf2 and its cytoplasmic anchor protein, Keap1, are central regulators of the cellular antioxidant response. Here, we investigated the role of the Nrf2-Keap1 pathway in photoageing using nrf2 gene-deficient (nrf2(-/-)) mice. Our results indicated that UVB-irradiated nrf2(-/-) mice showed accelerated photoageing, such as coarse wrinkle formation, loss of skin flexibility, epidermal thickening and deposition of extracellular matrix in the upper dermis. In addition, nrf2(-/-) mice also showed an increase in cutaneous reactivity for the lipid peroxidation product 4-hydroxy-2-nonenal and a significant decrease in cutaneous glutathione level. These findings indicate that Nrf2 plays the important role in the protection against UVB-induced photoageing.
authors.affiliation: Department of Dermatology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Hirota
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawachi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Koga
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hamada
authors.forename: Fujio
authors.initials: F
authors.lastname: Otsuka
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006984:Hypertrophy / Q000473:pathology; D000072019:Kelch-Like ECH-Associated Protein 1; D015227:Lipid Peroxidation / Q000528:radiation effects; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D023421:Models, Animal; D051267:NF-E2-Related Factor 2 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D015595:Skin Aging / Q000473:pathology* / Q000528:radiation effects*; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000447:Aldehydes; D000975:Antioxidants; D003598:Cytoskeletal Proteins; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D005978:Glutathione; C027576:4-hydroxy-2-nonenal