Elucidation of ultraviolet radiation-induced physiological degradation pathway of eumelanin and pheomelanin and its physiological significance

• Project/Area Number: 26461705
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Fujita Health University
• Principal Investigator: ITO Shosuke 藤田保健衛生大学, その他部局等, 名誉教授 (70121431)
• Co-Investigator(Kenkyū-buntansha): 若松 一雅 藤田保健衛生大学, 保健学研究科, 教授 (80131259)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: メラニン / 紫外線 / ユーメラニン / フェオメラニン / UVA

Outline of Final Research Achievements

Melanin is classified into black eumelanin and reddish pheomelanin. Our study aimed at elucidating UVA(and blue light)-induced degradation of both melanins and its physiological significance. Using DHICA-melanin as a model of eumelanin, we showed that it is oxidized by UVA to form a quinone form and further oxidized to form a specific degradation product. We also showed that during these processes, superoxide radical and singlet oxygen are produced. We then showed that upon irradiation of 300-550 nm light, synthetic eumelanin and pheomelanin produce those reactive oxygen species which are rapidly trapped by melanin.

Research Products

• [Int'l Joint Research] Jagiellonian University(ポーランド)
• [Int'l Joint Research] Beiersdorf AG(ドイツ)
• [Int'l Joint Research] Jagiellonian University(ポーランド)
• [Int'l Joint Research] Beiersdorf AG(ドイツ)
• [Journal Article] Tyrosinase-catalyzed oxidation of the leukoderma-inducing agent raspberry ketone produces (E)-4-(3-oxo-1-butenyl)-1,2-benzoquinone (2017)
  • Author(s): S Ito, M Hinoshita, E Suzuki, M Ojika, K Wakamatsu
  • Journal Title: Chem Res Toxicol Volume: 30 Pages: 859-848
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pheomelanogenesis is promoted at a weakly acidic pH (2017)
  • Author(s): K Wakamatsu, A Nagao, M Watabe, K Nakao, S Ito
  • Journal Title: Pigment Cell Melanoma Res Volume: 30 Pages: 372-377
  • Peer Reviewed
• [Journal Article] Quantifying variation in human scalp hair fiber shape and pigmentation (2016)
  • Author(s): T Lasisi, S Ito, K Wakamatsu, CN Shaw
  • Journal Title: Amer J Phys Anthropol Volume: 160 Issue: 2 Pages: 341-352
  • DOI: 10.1002/ajpa.22971
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of shell colour pigments in marine snails Calculus pharaonius and C. margaritarius (Trochoidea; Gastropoda) (2016)
  • Author(s): ST Williams, S Ito, K Wakamatsu, T. Goral, NP Edwards, RA Wogelius, T Henkel, LFC de Oliveira, LF Maia, S Strekopytov, T Jeffries, DI Speiser, JT Marstin
  • Journal Title: PLOS ONE Volume: 11 Pages: 1-25
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Elemental characterization of melanin in feathers via synchrotron X-ray imaging and absorption spectroscopy (2016)
  • Author(s): NP Edwords, A van Veelen, J Anne, PL Manning, U Bergmann, WI Sellers, VM Egerton, D Sokoras, R, Anoso-Mori, K Wakamatsu, S Ito, RA Wogelius
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 1-10
  • DOI: 10.1038/srep34002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High brood patch temperature of less colorful, less pheomelanic female barn swallows Hirundo rustic (2016)
  • Author(s): M Hasegawa, E Arai, S Ito, K Wakamatsu
  • Journal Title: Ibis Volume: 158 Pages: 808-820
  • Peer Reviewed
• [Journal Article] Aerobic photo reactivity of synthetic eumelanins and pheomelanins: generation of singlet oxygen and superoxide anion (2016)
  • Author(s): G Szewczyk, A Zadlo, M Sarna, S Ito, K Wakamatsu, T Sarna
  • Journal Title: Pigment Cell Melanoma Res Volume: 29 Issue: 6 Pages: 669-678
  • DOI: 10.1111/pcmr.12514
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Rhododenol-induced leukoderma in a mouse model mimicking Japanese skin (2016)
  • Author(s): Y Abe, K Okura, M Kawaguchi, Y Hozumi, H Aoki, T Kunisada, S Ito, K Wakamatsu, K Matsunaga, T Suzuki
  • Journal Title: J Dermatol Sci Volume: 81 Pages: 35-43
  • Peer Reviewed
• [Journal Article] The metabolic fate of oath-quinones derived from catecholamine metabolites (2016)
  • Author(s): S Ito, Y Yamanaka, M Ojika, K Wakamatsu
  • Journal Title: Int J Mol Sci Volume: 17
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Roles of reactive oxygen species in UVA-induced oxidation of 5,6-dihydroxyindole-2-carboxylic acid-melanin as studied by differential spectrophotometric method (2016)
  • Author(s): S Ito, M Kukita, S Koike, G Szewczyk, M Sarna, A Zadlo, T Sarna, K Wakamatsu
  • Journal Title: Pigment Cell Melanoma Res Volume: 29 Issue: 3 Pages: 340-351
  • DOI: 10.1111/pcmr.12469
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dominant red coat color in Holstein cattle is associated with a messiness mutation in the costumer protein complex, subunit alpha (COPA) gene (2015)
  • Author(s): B Dorshorst, C Henegar, X Liao, et al.
  • Journal Title: PLOS ONE Volume: 10 Issue: 6 Pages: e0128969-e0128969
  • DOI: 10.1371/journal.pone.0128969
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] An insect with selective control of egg coloration. (2015)
  • Author(s): Abram, P. K., Guerra-Grenier, E., Després-Einspenner, M-L., Ito, S., Wakamatsu, K., Boivin, G., Brodeur, J.
  • Journal Title: Curr. Biol. Volume: 25 Issue: 15 Pages: 2007-2011
  • DOI: 10.1016/j.cub.2015.06.010
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus. (2015)
  • Author(s): Wakamatsu, K., Tabuchi, K., Ojika, M., Zucca, F. A., Zecca, L., Ito, S.
  • Journal Title: J. Neurochem. Volume: 135 Issue: 4 Pages: 768-776
  • DOI: 10.1111/jnc.13237
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A convenient screening method to differentiate phenolic skin whitening tyrosinase inhibitors from leukoderma-inducing phenols. (2015)
  • Author(s): Ito, S., Wakamatsu, K.
  • Journal Title: J. Dermatol. Sci. Volume: 80 Issue: 1 Pages: 18-24
  • DOI: 10.1016/j.jdermsci.2015.07.007
  • Peer Reviewed
• [Journal Article] Effects of rhododendron and its metabolic products on melanocytic cell growth (2015)
  • Author(s): M Okura, T Yamashita, Y Ishii-Osai, M Yoshikawa, Y Sumikawa, K Wakamatsu, S Ito
  • Journal Title: J Dermatol Sci Volume: 80 Issue: 2 Pages: 142-149
  • DOI: 10.1016/j.jdermsci.2015.07.010
  • Peer Reviewed / Open Access
• [Journal Article] Chemical analysis of constitutive pigmentation of human epidermis reveals constant eumelanin to pheomelanin ratio (2015)
  • Author(s): S Del Bino, S Ito, J Sok, Y Nakanishi, P Bastien, K Wakamatsu, F Bernerd
  • Journal Title: Pigment Cell Melanoma Res Volume: 28 Issue: 6 Pages: 707-717
  • DOI: 10.1111/pcmr.12410
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tyrosinase depletion prevents the maturation of melanosomes in the mouse hair follicle (2015)
  • Author(s): EK Paterson, TJ Fielder, GR MacGregor, S Ito, K Wakamatsu, D. Gillen, V. Eby, RE Boissy, AK Ganesan
  • Journal Title: PLOS ONE Volume: 10
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The slaty (slt/Dctslt) allele decreases the content of eumelanin, pheomelanin in the mouse hair. (2015)
  • Author(s): Hirobe, T., Ito, S., Wakamatsu, K.
  • Journal Title: Pigment Cell Melanoma Res. Volume: 29 Issue: 1 Pages: 110-112
  • DOI: 10.1111/pcmr.12427
  • Peer Reviewed
• [Journal Article] Melanins and melanogenesis: from pigment cells to human health and technological applications (2015)
  • Author(s): M d'Ischia, K Wakamatsu, F Cicoira, et al.
  • Journal Title: Pigment Cell Melanoma Res Volume: 28 Issue: 5 Pages: 520-544
  • DOI: 10.1111/pcmr.12393
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tyrosinase-catalyzed metabolism of rhododendron (RD) in B16 melanoma cells: production of RD-pheomelanin and covalent binding with thiol proteins (2015)
  • Author(s): S Ito, M Okura, Y Nakanishi, M Ojika, K Wakamatsu, T Yamashita
  • Journal Title: Pigment Cell Melanoma Res Volume: 28 Issue: 3 Pages: 296-307
  • DOI: 10.1111/pcmr.12363
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Degree of polymerization of 5,6-dihydroxyindole- derived eumelanin from chemical degradation study (2014)
  • Author(s): Okuda H, Yoshino K, Wakamatsu K, Ito S, Sota T
  • Journal Title: Pigment Cell Melanoma Res Volume: 27 Issue: 4 Pages: 664-667
  • DOI: 10.1111/pcmr.12254
  • Peer Reviewed
• [Journal Article] Tyrosinase-catalyzed oxidation of rhododendrol produces 2-methylchromane-6, 7-dione, the putative ultimate toxic metabolite: Implications for melanocyte toxicity. (2014)
  • Author(s): Ito S, Ojika M, Yamashita T, Wakamatsu K
  • Journal Title: Pigment Cell Melanoma Res Volume: 27(5) Issue: 5 Pages: 744-753
  • DOI: 10.1111/pcmr.12275
  • Peer Reviewed
• [Journal Article] Human tyrosinase is able to oxidize both enantiomers of rhododendrol. (2014)
  • Author(s): Ito S, Gerwat W, Kolbe L, Yamashita T, Ojika M, Wakamatsu K
  • Journal Title: Pigment Cell Melanoma Res Volume: 27(6) Issue: 6 Pages: 1149-1153
  • DOI: 10.1111/pcmr.12300
  • Peer Reviewed
• [Journal Article] Mineralized rods and cones suggest colour vision in a 300 Myr-old fossil fish (2014)
  • Author(s): Tanaka, G., Parker, A.R., Hasegawa, Y., Siveter, D.J., Yamamoto, R., Miyashita, K., Takahashi, Y., Ito, s., Wakamatsu, K., Mukuda, T., Matsuura, M., Tomikawa, K., Furutani, M., Suzuki, K., and Maeda, H.
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 5920-5920
  • DOI: 10.1038/ncomms6920
  • NAID: 120007016768
  • Peer Reviewed
• [Presentation] ロドデノールユーメラニンは強い酸化促進作用をもつ (2016)
  • Author(s): 伊藤祥輔、黄倉真恵、若松一雅、山下利春
  • Organizer: 第27回日本色素細胞学会学術大会
  • Place of Presentation: 岐阜大学サテライトキャンパス、岐阜市
  • Year and Date: 2016-11-12
• [Presentation] N-Acewtylcysteine (NAC)は紫外線によるロドデノールの色素細胞障害性増強効果を軽減する (2016)
  • Author(s): 後藤典子、辻本昌理子、永井宏、正木太朗、伊藤祥輔、若松一雅、錦織千佳子
  • Organizer: 第27回日本色素細胞学会学術大会
  • Place of Presentation: 岐阜大学サテライトキャンパス、岐阜市
  • Year and Date: 2016-11-12
• [Presentation] カテコールアミン代謝物のオルトキノン体の反応性の比較 (2016)
  • Author(s): 若松一雅、山中佑太、田中ひとみ、小鹿一、伊藤祥輔
  • Organizer: 第27回日本色素細胞学会学術大会
  • Place of Presentation: 岐阜大学サテライトキャンパス、岐阜市
  • Year and Date: 2016-11-12
• [Presentation] The metabolic fate of oath-quinones derived from catecholamine metabolites (2016)
  • Author(s): S Ito, Y Yamanaka, M Ojika, K Wakamatsu
  • Organizer: 20th European Society of Pigment Cell Research Meeting
  • Place of Presentation: Milan, Italy
  • Year and Date: 2016-09-12
  • Int'l Joint Research / Invited
• [Presentation] Biochemical mechanism of rhododendrol-induced leukoderma (2016)
  • Author(s): S Ito
  • Organizer: 20th European Society of Pigment Cell Research Meeting
  • Place of Presentation: Milan, Italy
  • Year and Date: 2016-09-12
  • Int'l Joint Research / Invited
• [Presentation] Mechanism of rhododendrol-induced leukoderma (2016)
  • Author(s): S Ito
  • Organizer: Genmedskin 2016
  • Place of Presentation: New Delhi, India
  • Year and Date: 2016-06-24
  • Int'l Joint Research / Invited
• [Presentation] メラニン産生細胞におけるロドデノールの代謝 (2015)
  • Author(s): 伊藤祥輔
  • Organizer: 第26回日本色素細胞学会
  • Place of Presentation: 札幌医科大学（札幌）
  • Year and Date: 2015-11-14
  • Invited
• [Presentation] メラニン産生細胞におけるロドデノールの代謝 (2015)
  • Author(s): 伊藤祥輔
  • Organizer: 第114回日本皮膚科学会総会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2015-05-30
  • Invited
• [Presentation] Tyrosinase-catalyzed oxidation of rhododendron produces a cyclic quinone, the ultimate toxic metabolite: implications for melanocyte toxicity (2014)
  • Author(s): S Ito, M Ojika, T Yamashita, K Wakamatsu
  • Organizer: The 22nd International Pigment Cell Conference
  • Place of Presentation: シンガポール
  • Year and Date: 2014-09-04 – 2014-09-07
• [Book] 色素細胞第２版ー基礎から臨床へー (2015)
  • Author(s): 塚本克彦、伊藤祥輔
  • Total Pages: 12
  • Publisher: 慶應義塾大学出版会
• [Book] 色素細胞第２版ー基礎から臨床へー (2015)
  • Author(s): 若松一雅、伊藤祥輔
  • Total Pages: 20
  • Publisher: 慶應義塾大学出版会