| Project/Area Number |
15591167
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
KAWACHI Yasuhiro University of Tsukuba, Graduate School of Comprehensive Human Sciences, Associate Professor, 大学院・人間総合科学研究科, 助教授 (00272196)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Nrf2 / ROS / UV / UVA / UVB / アポトーシス |
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| Research Abstract |
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 photoaging and diseases of the skin. Transcription factor Nrf2 and its cytoplasmic anchor protein Keap1 are central regulators of the cellular antioxidant response. We investigated in this study 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. The nuclear accumulation of Nrf2 induced by UVA was enhanced by the photosensitizer hematoporphyrin, suggesting that Nrf2 activation is mediated by singlet oxygen. To evaluate the protective role of Nrf2 against UVA radiation, we examined UVA-induced apoptosis using dermal fibroblasts derived from nrf2 and/or keap1 gene knockout mice. While disruption of nrf2 increased the number of apoptotic cells following UVA irradiation, disruption of keap1 decreased the apoptotic cell number 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.
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