| Project/Area Number |
17591157
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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) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Nrf2 / ROS / UV / photocarcinogenesis / sunburn / 光老化 |
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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 Keap 1 are central regulators of the cellular antioxidant response. We investigated in this study the roles of Nrf2-Keap 1 system in protection of skin tissue from harmful effects of UVB irradiation using nrf2-deficient mice. A single irradiation with UVB induced stronger and longer-lasting sunburn reaction in nrf2-deficient mice. Histological changes including epidermal necrosis, dermal edema and inflammatory cell infiltration, sunburn cell formation and TUNEL-positive apoptotic cell formation, and accumulation of oxidative DNA products such as 8-hydroxy-2'-deoxyguanosine after UVB radiation were more prominent in nrf2-deficient mice. These findings thus demonstrate that the Nrf2-Keap 1 pathway plays an important role in the protection of the skin against acute UVB reactions including cutaneous cell apoptosis and oxidative damages of skin. However, chronic UVB irradiation resulted in no significant difference in skin carcinogenesis between nrf2-deficient and wild-type mice, suggesting a complicate and subtle balance between promoting and protecting factors of photocarcinogenesis.
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