Chemical structure of neuromelanin : an elucidation to the production process

2008 Fiscal Year Final Research Report

• Project/Area Number: 19500332
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Fujita Health University
• Principal Investigator: KAZUMASA Wakamatsu Fujita Health University, 医療科学部, 教授 (80131259)
• Co-Investigator(Kenkyū-buntansha): SHOSUKE Ito 藤田保健衛生大学, 医療科学部, 教授 (70121431)
• Project Period (FY): 2007 – 2008
• Keywords: 分子 / 細胞 / 神経生物学 / ドーパミン / ドーパ / HPLC

Research Abstract

ヒト中脳黒質中に存在するニューロメラニン)NM)を単離し、その構造研究を行った。その結果、NMはDAとCysが約4:1で酸化重合して生成したフェオメラニンの構造単位であるベンゾチアジンを持つ部分とDAの酸化重合で得られたユーメラニンの構造単位からなることがわかった。また、脳内被殻、前運動野皮質、小脳などの非カテコールアミン作動性ニューロンにおいて新しいNM様色素が存在することを発見した。この色素は、黒質や青斑核に存在するNMと違って、DA由来でなくDOPA由来であることが化学分解法とHPLC分析により確認された。

Research Products

• [Journal Article] New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals (2008)
  • Author(s): Zecca, L., Chiara, B., Ito, S., Wakamatsu, K. (他14名)
  • Journal Title: Proc. Natl. Acad. Sci. 105 Pages: 17567-17572
  • Peer Reviewed
• [Journal Article] Characterization of melanin in human iridal and choroidal melanocytes from eyes with various colored irides (2008)
  • Author(s): Wakamatsu, K., Hu, D-N., McCormick, SA., Ito, S.
  • Journal Title: Pigment Cell Res 21 Pages: 97-105
  • Peer Reviewed
• [Journal Article] Chemistry of mixed melanogenesis - pivotal roles of dopaquinone (2008)
  • Author(s): Ito S, Wakamatsu K.
  • Journal Title: Photochem Photobiol 84 Pages: 582-592
  • Peer Reviewed
• [Journal Article] Regulation of eumelanin/pheomelanin synthesis and visible pigmentation in melanocytes by ligands of the melanocortin 1 receptor (2008)
  • Author(s): Wakamatsu, K., Ito, S., Wolber, R., Hearing, VL.
  • Journal Title: Le Pape E, Pigment Cell Melanoma Res 21 Pages: 477-486
  • Peer Reviewed
• [Journal Article] Pigmentation effects of solar-simulated radiation as compared with UVA and UVB radiation (2008)
  • Author(s): Wolber, R., Schlenz, K., Wakamatsu, K., Smuda, C., Ito, S (他2名)
  • Journal Title: Pigment Cell Melanoma Res 21 Pages: 487-491
  • Peer Reviewed
• [Journal Article] Unexpected endocrine features and normal pigmentation in a young adult patient carrying a novel homozygous mutation in the POMC gene (2008)
  • Author(s): Clement, K., Dubern, B., Ito, S., Wakamatsu, K. (他5名)
  • Journal Title: J Clin Endocrin Metab doi : 10. 1210/jc Pages: 2008-1164
  • Peer Reviewed
• [Journal Article] Adaptive melanin response of the soil fungus Aspergillus niger to UV radiation stress at "Evolution Canyon", Mount Carmel, Israel (2008)
  • Author(s): Singaravelan, N., Grishkan, I., Beharav, A., Wakamatsu, K., Ito, S., Nevo, E.
  • Journal Title: Plos One 3(8) Pages: e2993
  • Peer Reviewed
• [Journal Article] TRP-2 expression protects HEK cells from dopamine- and hydroquinone-induced toxicity (2008)
  • Author(s): Michard, Q., Commo, S., Rocchetti, J., El Houari, F., Alleaume, A. M., Wakamatsu, K., Ito, S., Bernard, B. A.
  • Journal Title: Free Radic Biol Med 45 Pages: 1002-1010
  • Peer Reviewed
• [Journal Article] Corticsterone mediates the condition-dependent component of melanin-based coloration (2008)
  • Author(s): Roulin A., Almasi, B., Rossi-Pedruzzi, A., Ducrest, A-L., Wakamatsu, K., Miksik, I., Blount, JD., Jenni-Eiermann., Jenni, L.
  • Journal Title: Animal Behaviour 75 Pages: 1351-1358
  • Peer Reviewed
• [Journal Article] Possible oxidative polymerization mechanism of 5,6-dihydroxyindole from ab initio calculations (2008)
  • Author(s): Okuda, H., Wakamatsu, K., Ito, S., Sota, T.
  • Journal Title: J. Phys. Chem. A. 112 Pages: 11213-11222
  • Peer Reviewed
• [Journal Article] Ckin. Exp (2008)
  • Author(s): Kikuchi, K., Wakamatsu, K., Tada, Y., Komine, M., Ito, S., Tamaki, K.
  • Journal Title: Dermatol 33(6) Pages: 750-753
  • Peer Reviewed
• [Journal Article] Pael receptor is involved in dopamine metabolism in the nigrostriatal system. Imai Y, Inoue H (2007)
  • Author(s): Wakamatsu K, Ito S, Takahashi R (他14名)
  • Journal Title: Nurosci. Res. 59 Pages: 413-425
  • Peer Reviewed
• [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): Kitao Y, Imai Y, Wakamatsu K, Ito S (他14名)
  • Journal Title: Hum Mol Genet 16 Pages: 50-60
  • Peer Reviewed
• [Journal Article] High levels of melanin-related metabolites in plasma from pink-eyed dilution mice (2007)
  • Author(s): Wakamatsu K, Hirobe T, Ito S.
  • Journal Title: Pigment Cell Res 20 Pages: 222-224
  • Peer Reviewed
• [Journal Article] Childhood malnutrition is associated with a reduction in the total melanin content of scalp hair (2007)
  • Author(s): Mckenzie CA, Wakamatsu K, Hanchard NA, Forrester T, Ito S.
  • Journal Title: Br. J. Nutr 98 Pages: 159-164
  • Peer Reviewed
• [Journal Article] Excess tyrosine stimulates eumelanin and pheomelanin synthesis in cultured slaty melanocytes from neonatal mouse epidermis (2007)
  • Author(s): Hirobe T, Wakamatsu K, Ito S.
  • Journal Title: Zool. Sci. 24 Pages: 209-217
  • Peer Reviewed
• [Journal Article] Mid-infrared absorption spectrum of 5,6-dihydroxyindole-2-carboxylic acid (2007)
  • Author(s): Okuda H, Nakamura A, Wakamatsu K, Ito S, Sota T.
  • Journal Title: Chem. Phys. Lett 433 Pages: 355-359
  • Peer Reviewed
• [Journal Article] Regulation of human skin pigmentation and responses to ultraviolet radiation (2007)
  • Author(s): Miyamura Y, Wakamatsu K, Ito S (他11名)
  • Journal Title: Pigment Cell Res 20 Pages: 2-13
  • Peer Reviewed
• [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): Kitao, Y., Imai, Y., Ozawa. K., Wakamatsu, K., Ito, S., (他10名)
  • Journal Title: Hum Mol Genet 16 Pages: 50-60
  • Peer Reviewed
• [Journal Article] The eumelanin and pheomelanin contents in dorsal hairs of female recessive yellow mice are greater than in male (2007)
  • Author(s): Hirobe. T., Wakamatsu, K., Ito, S.
  • Journal Title: J. Dermatol. Sci. 45 Pages: 55-62
  • Peer Reviewed
• [Journal Article] 4-S-Cysteaminylphenol-loaded magnetite cationic liposomes for combination therapy of hyperthermia with chemotherapy against malignant melanoma (2007)
  • Author(s): Ito, A., Fujioka, M., Yoshida T., Wakamatsu, K., Ito, S., Yamashita, T., Jimbow, K., Honda, H.
  • Journal Title: Cancer Sci 98 Pages: 424-430
  • Peer Reviewed
• [Journal Article] A melanin-based trait reflects environmental growth conditions of nestling male Eurasian kestrels (2007)
  • Author(s): Fargallo, J. A., Laaksonen, T., Korpimaki, E., Wakamatsu, K.
  • Journal Title: Envol Ecol 21 Pages: 157-171
  • Peer Reviewed
• [Journal Article] Excess tyrosine stimulates eumelanin and pheomelanin synthesis in cultured slaty melanocytes from neonatal mouse epidermis (2007)
  • Author(s): Hirobe, T., Wakamatsu, K., Ito, S.
  • Journal Title: Zool. Sci. 24 Pages: 209-217
  • Peer Reviewed
• [Journal Article] Childhood malnutrition is associated with a reduction in the total melanin content of scalp hair (2007)
  • Author(s): McKenzie, C. A., Wakamatsu, K., Hanchard, N. A., Forrester, T., Ito, S.
  • Journal Title: Br. J. Nutr. 98 Pages: 159-164
  • Peer Reviewed
• [Journal Article] Comparison of the quantity of cochlear melanin in young and old C57BL/6 mice. Arch. Otolaryngol (2007)
  • Author(s): Hayashi, H., Sone, M., Schachern, P. A., Wakamatsu, K., Paparella, M. M., Nakashima, T.
  • Journal Title: Head Neck Surg 133 Pages: 151-154
  • Peer Reviewed
• [Journal Article] Mid-infrared absorption spectrum of 5, 6-dihydroxyindole-2-carboxylicacid. (2007)
  • Author(s): Okuda, H., Nakamura, A., Wakamatsu, K., Ito, S., Sota, T.
  • Journal Title: Chem. Phys. Lett 433 Pages: 355-359
  • Peer Reviewed
• [Journal Article] High levels of melanin-related metabolites in plasma from pink-eyed dilution mice (2007)
  • Author(s): Wakamatsu, K., Hirobe, T., Ito, S.
  • Journal Title: Pigment Cell Res 20 Pages: 222-224
  • Peer Reviewed
• [Journal Article] Excess tyrosine rescues activity of proliferation and differentiation of cultures recessive yellow melanocytes derived from neonatal epidermis (2007)
  • Author(s): Hirobe, T., Abe, H., Wakamatsu, K., Ito, S., Kawa, Y., Soma, Y., Mizoguchi, M.
  • Journal Title: Eur. J. Cell Biol. 86 Pages: 315-330
  • Peer Reviewed
• [Journal Article] The melanogenic system of the liver pigmented macrophages of Rana esculenta L. -tyrosine activity (2007)
  • Author(s): Gallone, A., Sagliano, A., Guida, G., Ito, S., Wakamatsu, K., Capozzi, V., Pema, G., Zanna, P., Cicero, R.
  • Journal Title: Histol. Histopathol 22(10) Pages: 1065-1075
  • Peer Reviewed
• [Journal Article] Serum levels of pigmentation markers are elevated in patients undergoing hemodialysis (2007)
  • Author(s): Murakami, K., Wakamatsu, K., Nakanishi, Y., Takahashi, H., Sugiyama, S., Ito, S.
  • Journal Title: Blood Purif 25 Pages: 483-489
  • Peer Reviewed
• [Journal Article] Pael receptor is involved in dopamine metabolism in the nigrostriatal system (2007)
  • Author(s): Imai, Y., Inoue, H., Wakamatsu, K., Ito, S., (他15名)
  • Journal Title: Nurosci. Res. 59 Pages: 413-425
  • Peer Reviewed
• [Journal Article] Characterization of melanin in human iridal and choroidal melanocytes from eyes with various colored irides (2007)
  • Author(s): Wakamatsu, K., Hu, D-N., McCormick, S.A., Ito, S.
  • Journal Title: Pigment Cell Melanoma Res 21 Pages: 97-105
  • Peer Reviewed
• [Presentation] Reexamination of microanalytical methods for melanin assay (2008)
  • Author(s): Wakamatsu, K
  • Organizer: Conjoint Meeting of XXth International Pigment Cell Conference & Vth International Melanoma Research Congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20080507-12
• [Presentation] Quantitative analysis of eumelanin and pheomelanin in humans, mice, and other animals (2008)
  • Author(s): Wakamatsu, K
  • Organizer: Conjoint Meeting of XXth International Pigment Cell Conference & Vth International Melanoma Research Congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20080507-12
• [Presentation] Serum melanin-related metabolites levels in psoriasis patients undergoing narrowband ultraviolet B phototherapy (2008)
  • Author(s): Kikuchi, K
  • Organizer: Conjoint Meeting of XXth International Pigment Cell Conference & Vth International Melanoma Research Congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20080507-12
• [Presentation] Does the sexual difference in the feather color of Jungle Crows (Corvus macrorthynchos) exist? (2008)
  • Author(s): Lee, E
  • Organizer: Conjoint Meeting of XXth International Pigment Cell Conference & Vth International Melanoma Research Congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20080507-12
• [Presentation] Comparison of melanogenesis in cultured epidermal melanocytes from wild-type and mutant mice at the slaty locus (2008)
  • Author(s): Niki, Y
  • Organizer: Conjoint Meeting of XXth International Pigment Cell Conference & Vth International Melanoma Research Congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20080507-12
• [Presentation] Reactivity of 5,6-dihydroxyindole, its homodimers, and their two-electron-oxidants from ab initio (2008)
  • Author(s): Okuda, H
  • Organizer: Conjoint Meeting of XXth International Pigment Cell Conference & Vth International Melanoma Research Congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20080507-12
• [Presentation] Agouti protein modifies melanocyte shape and melanogenesis through camp-independent signaling pathway (2008)
  • Author(s): Hida, T
  • Organizer: Conjoint Meeting of XXth International Pigment Cell Conference & Vth International Melanoma Research Congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20080507-12
• [Presentation] Regulation of melanocytes fate by an agonist inverse of MC1R, agouti protein (2008)
  • Author(s): Le Pape, E
  • Organizer: Conjoint Meeting of XXth International Pigment Cell Conference & Vth International Melanoma Research Congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20080507-12
• [Presentation] Intratumoral administration of melanoma-targeting N-propionyl cysteaminylphenol induces in vivo anti-melanoma effect and tumor specific immunity (2008)
  • Author(s): Osai, Y
  • Organizer: Conjoint Meeting of XXth International Pigment Cell Conference & Vth International Melanoma Research Congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20080507-12
• [Presentation] 5-S-cysteinyldopa (5-S-CD) value in malignant melanoma cases at Kumamoto University (2008)
  • Author(s): Inoue, Y
  • Organizer: Conjoint Meeting of XXth International Pigment Cell Conference & Vth International Melanoma Research Congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20080507-12
• [Presentation] メラニンの微量分析法の再検討 (2007)
  • Author(s): 若松一雅
  • Organizer: 第21回日本色素細胞学会学術大会
  • Place of Presentation: 愛知県豊明市
  • Year and Date: 2007-12-09
• [Presentation] ヒト皮膚モデルに於けるユーメラニンとフェオメラニンの化学的定量 (2007)
  • Author(s): 古川雅代
  • Organizer: 第21回日本色素細胞学会学術大会
  • Place of Presentation: 愛知県豊明市
  • Year and Date: 2007-12-09
• [Presentation] 第一原理計算からの5, 6-dihydroxyindoleの二量体化機構 (2007)
  • Author(s): 奥田英和
  • Organizer: 第21回日本色素細胞学会学術大会
  • Place of Presentation: 愛知県豊明市
  • Year and Date: 2007-12-09
• [Presentation] 部分的金髪症の一例 : メラニン定量分析と基礎病変についての考察 (2007)
  • Author(s): 塚本克彦
  • Organizer: 第21回日本色素細胞学会学術大会
  • Place of Presentation: 愛知県豊明市
  • Year and Date: 2007-12-09
• [Presentation] マグネタイト結合型システアミニールフェノール(NPrCAP/M)のメラノーマ細胞親和性と細胞死誘導 (2007)
  • Author(s): 佐藤牧人
  • Organizer: 第21回日本色素細胞学会学術大会
  • Place of Presentation: 愛知県豊明市
  • Year and Date: 2007-12-09
• [Presentation] メラノーマ標的ナノパーティクルNPrCAP/Mを用いた化学温熱免疫(CTI)療法における腫瘍免疫機構の解析 (2007)
  • Author(s): 酒本亜紀子
  • Organizer: 第21回日本色素細胞学会学術大会
  • Place of Presentation: 愛知県豊明市
  • Year and Date: 2007-12-09
• [Presentation] Exploitation of melanogenesis can provide tyrosinase-targeted drug delivery system and Chemo-thermo-immunotherapy with NPrCAP-magnetite for melanoma patients (2007)
  • Author(s): Kowichi, J.
  • Organizer: 第21回日本色素細胞学会学術大会
  • Place of Presentation: 愛知県豊明市
  • Year and Date: 2007-12-09
• [Presentation] 熊本大学皮膚科におけるメラノーマ患者350例の5-S-CD値について (2007)
  • Author(s): 井上雄二
  • Organizer: 第21回日本色素細胞学会学術大会
  • Place of Presentation: 愛知県豊明市
  • Year and Date: 2007-12-09
• [Presentation] ナローバンドUVB療法中尋常性乾癬患者の血清中5-S-cysteinyldopa値の変化 (2007)
  • Author(s): 菊池かな子
  • Organizer: 第21回日本色素細胞学会学術大会
  • Place of Presentation: 愛知県豊明市
  • Year and Date: 2007-12-09
• [Presentation] アグーチ蛋白質はcAMP非依存性にメラノサイトの形態を変化させる (2007)
  • Author(s): 肥田時征
  • Organizer: 第21回日本色素細胞学会学術大会
  • Place of Presentation: 愛知県豊明市
  • Year and Date: 2007-12-09
• [Presentation] Chemistry of mixed melanogenesis : pivotal role of dopaquinone (2007)
  • Author(s): Ito, S
  • Organizer: 14th Meeting of European Society for Pigment Cell Research
  • Place of Presentation: Bari, Italy
  • Year and Date: 2007-10-14
• [Presentation] Excess tyrosine rescues the reduced activity of the proliferation and differentiation of cultured recessive yellow melanocytes of neonatal mouse epidermis (2007)
  • Author(s): Hirobe, T
  • Organizer: 14th Meeting of European Society for Pigment Cell Research
  • Place of Presentation: Bari, Italy
  • Year and Date: 2007-10-14
• [Presentation] ICR雄性マウスへのアロエエモジン35日間混餌投与の影響 (2007)
  • Author(s): 新保寛
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-10-03
• [Presentation] 加齢とともに毛色変化を起こす変異体マウスの解析 (2007)
  • Author(s): 佐藤康成
  • Organizer: 第79回日本遺伝学会
  • Place of Presentation: 岡山市
  • Year and Date: 2007-09-19
• [Presentation] in vitro皮膚組織モデルを用いた分光学的メラニン色素濃度定量法の検討 (2007)
  • Author(s): 中村厚
  • Organizer: 第54回応用物理学関係連合講演会
  • Place of Presentation: 東京
  • Year and Date: 2007-03-27