TY - JOUR
T1 - Ultraviolet A irradiation induces NF-E2-related factor 2 activation in dermal fibroblasts
T2 - Protective role in UVA-induced apoptosis
AU - Hirota, Ayako
AU - Kawachi, Yasuhiro
AU - Itoh, Ken
AU - Nakamura, Yasuhiro
AU - Xu, Xuezhu
AU - Banno, Tomohiro
AU - Takahashi, Takenori
AU - Yamamoto, Masayuki
AU - Otsuka, Fujio
N1 - Funding Information:
Our study was supported in part by a grant from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (15591084 to Y. Kawachi).
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Keap1
KW - Nrf2
KW - UVA
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U2 - 10.1111/j.0022-202X.2005.23670.x
DO - 10.1111/j.0022-202X.2005.23670.x
M3 - Article
C2 - 15816842
AN - SCOPUS:16844375366
VL - 124
SP - 825
EP - 832
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 4
ER -