Ultraviolet A Irradiation Induces NF-E2-Related Factor 2 Activation in Dermal Fibroblasts: Protective Role in UVA-Induced Apoptosis
| Autor: | Yasuhiro Kawachi, Masayuki Yamamoto, Xuezhu Xu, Takenori Takahashi, Yasuhiro Nakamura, Ayako Hirota, Tomohiro Banno, Fujio Otsuka, Ken Itoh |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Keap1
medicine.medical_specialty Programmed cell death NF-E2-Related Factor 2 Ultraviolet Rays Glutamate-Cysteine Ligase Apoptosis Dermatology Biology environment and public health Biochemistry Nrf2 Gene Expression Regulation Enzymologic Skin Aging Mice chemistry.chemical_compound medicine Animals Molecular Biology Transcription factor Cells Cultured Adaptor Proteins Signal Transducing Cell Nucleus chemistry.chemical_classification Hematoporphyrin Mice Inbred ICR Reactive oxygen species Kelch-Like ECH-Associated Protein 1 Dermis Cell Biology Fibroblasts respiratory system KEAP1 Mice Mutant Strains DNA-Binding Proteins Cytoskeletal Proteins Hematoporphyrins UVA chemistry Knockout mouse ComputingMethodologies_DOCUMENTANDTEXTPROCESSING Trans-Activators Cancer research sense organs |
| Zdroj: | Journal of Investigative Dermatology. 124:825-832 |
| ISSN: | 0022-202X |
| DOI: | 10.1111/j.0022-202x.2005.23670.x |
| Popis: | application/pdf Ultraviolet (UV) radiation is one of the most important environmental factors involved in the pathogenesis of skin aging and cancer. Many harmful effects of UV radiation are associated with the generation of reactive oxygen species, and cellular antioxidants act to prevent the occurrence and reduce the severity of UV-induced skin disorders. Transcription factor NF-E2-related Factor 2 (Nrf2) and its cytoplasmic anchor protein Kelch-like-ECH-associated protein 1 (Keap1) are central regulators of the cellular antioxidant response. In this study, we investigated the effects of UV irradiation on the activation of Nrf2 in dermal fibroblasts. We found that UVA irradiation, but not UVB, causes nuclear translocation and accumulation of Nrf2 by a factor of 6.5 as compared with unirradiated controls. The nuclear accumulation of Nrf2 induced by UVA was enhanced by the photosensitizer hematoporphyrin. To evaluate the protective role of Nrf2 against UVA radiation, we examined UVA-induced apoptosis using dermal fibroblasts derived from nrf2 or keap1 gene knockout mice. Whereas disruption of nrf2 increased the number of apoptotic cells following UVA irradiation by 1.7-fold, disruption of keap1 decreased the apoptotic cell number by half as compared with wild-type controls. These findings thus demonstrate that the Nrf2–Keap1 pathway plays an important role in the protection of the skin against UVA irradiation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|