Mechanism of regulation of melanin synthesis by coat color genes and ultraviolet radiation in mice and human
| Project/Area Number |
18591262
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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 | Fujita Health University |
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Principal Investigator |
ITO Shosuke Fujita Health University, School of Health Sciences, Professor (70121431)
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| Co-Investigator(Kenkyū-buntansha) |
WAKAMATSU Kazumasa Fujita Health University, School of Health Science, Professor (80131259)
HIROBE Tomohisa National Institute of Radiological Sciences, Radiation Effect Mechanism Research Group, Team Leader (10111238)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | melanocyte / melanoblast / keratinocyte / serum-free culture / slaty / recessive yellow / skin / melanin / ブラック / メラノソーム / リセッシブイェロー |
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| Research Abstract |
In black melanocytes (Dct^+), almost all melanosomes were elliptical stage IV melanosomes. However, in slaty (Dctslt) melanocytes, numerous spherical stage III melanosomes with globular depositions of pigment in addition to elliptical stage III melanosomes with intralumenal fibrils were observed. In slaty melanocytes, spherical melanosomes were gradually decreased after birth, whereas elliptical melanosomes were gradually increased. Stage IV melanosomes were very few in slaty melanocytes, and were not increased after birth. L-tyrosine increased the elliptical stage IV melanosomes, and eumelanin and pheomelanin synthesis. These results suggest that the slaty mutation blocks the melanosome maturation at stage III and affects the melanosome morphology and L-tyrosine restores these abnormalities.
The recessive yellow (Mclre) melanocytes produced mainly eumelanin in our culture system. The proliferation of recessive yellow melanocytes was decreased compared with that of wild-type at the e-locus, black melanocytes. The differentiation of melanocytes was also delayed and inhibited in recessive yellow mice. Tyrosinase (TYR) activity and TYR-related protein 1 (TRP1) and TRP2 (dopachrome tautomerase, DCT) expressions were decreased and, in addition, the maturation of stage IV melanosomes was inhibited. Excess L-tyrosine (Tyr) added to the culture media rescued the reduced activity of proliferation of melanocytes. L-Tyr also stimulated TYR activity and TRP1 and TRP2 expressions as well as the maturation of stage IV melanosomes and pigmentation. These results suggest that the Mclre mutation affects the proliferation and differentiation of melanocytes and L-Tyr rescues the reduced proliferative and differentiative activities by stimulating TYR activity and TRP1 and TRP2 expressions as well as melanosome maturation.
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Report
(3 results)
Research Products
(97 results)
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[Journal Article] Regulation of human skin pigmentation and responses to ultraviolet radiation.2007
Author(s)
Y. Miyamura, S. G. Coelho, R. Wolber, S. A. Miller, K. Wakamatsu, B. Z. Zmudzka, S. Ito, C. Smuda, T. Passeron, W. Choi, J. Batzer, Y. Yamaguchi, J. Z. Beer, V. J. Hearing.
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Journal Title
Pigment Cell Res 20
Pages: 2-13
Description
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[Journal Article] Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation.2007
Author(s)
Y. Kitao, Y. Imai, K. Ozawa, A. Kataoka, T. Ikeda, M. Soda, K. Nakimawa, H. Kiyama, D. M. Stern, O. Hori, K. Wakamatsu, S. Ito, S. Itohara, R. Takahashi, S. Ogawa.
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Journal Title
Hum Mol Genet. 16
Pages: 50-60
Description
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[Journal Article] Pael receptor is involved in dopamine metabolism in the nigrostriatal system.2007
Author(s)
Y. Imai, H. Inoue, A. Kataoka, W. Hua-Qin, M. Masuda, T. Ikeda, K. Tsukita, M. Soda, T. Kodama, T. Fuwa, Y. Honda, S. Kaneko, S. R. Takahashi.
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Journal Title
Nurosci. Res. 59
Pages: 413-425
Description
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[Journal Article] Topical drug rescue strategy and skin protection based on the role of Mclr in UV-induced tanning.2006
Author(s)
J. A. D'Orazio, T. Nobuhisa, R. Cui, M. Arya, M. Spry, K. Wakamatsu, V. Igras, T. Kunisada, S. R. Granter, E. K. Nishimura, S. Ito, D. E. Fisher.
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Journal Title
Nature 443(21)
Pages: 340-344
Description
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[Presentation] メラニンの微量分液法の再検討2007
Author(s)
若松 一雅、伊藤 祥輔、M.Brilliant
Organizer
第21回日本色素細胞学会学術大会
Place of Presentation
豊明、日本
Year and Date
2007-12-09
Description
「研究成果報告書概要(和文)」より
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[Presentation] 「研究成果報告書概要(欧文)」より2007
Author(s)
T. Hida, K. Wakamatsu, S. Ito, E. V. Sviderskaya, L. Montoliu, G. L. Millhauser, B. Yu, G. S. Barsh, K. Jimbow, D. C. Bennett.
Organizer
The 21th Annual Meeting of the Japanese Society for Pigment Cell Research
Place of Presentation
Toyoake
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[Presentation] Gene polymorphism and human pigmentation2006
Author(s)
M.H.Brilliant, J.B.Walsh, M.S.Hendersonh, et. al.
Organizer
The 13th Annual Meeting of the PanAmerican Society for Pigment Cell Research
Place of Presentation
Cincinnati,USA
Year and Date
2006-09-07
Description
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[Presentation] Eumelanin induction in a MC1R-deficient transgenic animal model by topical application of forskolin.2006
Author(s)
J. D'Orazio, T. Nobuhisa, R. Cui, E. Nishimura, M. Spry, T. Kunisada, K. Wakamatsu, S. Ito, S. Granter, M. Arya, D. Fisher.
Organizer
The 13th Annual Meeting of the PanAmerican Society for Pigment Cell Research
Place of Presentation
Cincinnati, USA
Description
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[Presentation] Gene polymorphism and human pigmentation.2006
Author(s)
M. H. Brilliant, J. B. Walsh, M. S. Hendersonh, R. K. Valenzuela, M. H. Kim, N. A. Garrison, J. T. Kelch, C. L. Williams, J. M. Fabian, D. K. Smith, B. S. Metelits, 0. Cohen-Barak, D. T. Erickson, F. J. Meaney, K. Wakamatsu, S. Ito, K. C. Cheng.
Organizer
The 13th Annual Meeting of the PanAmerican Society for Pigment Cell Research
Place of Presentation
Cincinnati, USA
Description
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[Presentation] Residual function of the truncated Mclr encoded by the murine recessive yellow allele.2006
Author(s)
F. Rouzaud, ELe Pape, J. Valencia, G-E. Costin, W. Berens, H. Watabe, M. Abu-Asab, K. Wakamatsu, S. Ito, V. J. Hearing.
Organizer
The 13th Annual Meeting of the PanAmerican Society for Pigment Cell Research
Place of Presentation
Cincinnati, USA
Description
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