Mechanism of regulation of melanin synthesis by coat color genes and ultraviolet radiation in mice and human

毛色基因和紫外线调节小鼠和人类黑色素合成的机制

• 批准号: 18591262
• 负责人: ITO Shosuke
• 金额: $ 2.55万
• 依托单位: Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591262/
• 关键词: 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

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.

在黑色黑素细胞（Dct^+）中，几乎所有黑素体都是椭圆形 ​​IV 期黑素体。然而，在板岩 (Dctslt) 黑素细胞中，除了具有管腔内原纤维的椭圆形 III 期黑素体之外，还观察到许多具有色素球状沉积的球形 III 期黑素体。在板岩状黑素细胞中，出生后球形黑素体逐渐减少，而椭圆形黑素体逐渐增加。 IV期黑素体在板状黑素细胞中很少，并且在出生后不会增加。 L-酪氨酸增加椭圆IV期黑素体以及真黑素和褐黑素的合成。这些结果表明，slaty 突变阻止了 III 期黑素体的成熟，并影响黑素体形态，而 L-酪氨酸可以恢复这些异常。在我们的培养系统中，隐性黄色 (Mclre) 黑素细胞主要产生真黑素。与e位点黑色素细胞的野生型相比，隐性黄色黑色素细胞的增殖减少。在隐性黄色小鼠中，黑素细胞的分化也被延迟和抑制。酪氨酸酶（TYR）活性以及TYR相关蛋白1（TRP1）和TRP2（多巴色素互变异构酶，DCT）表达降低，此外，IV期黑素体的成熟受到抑制。培养基中添加过量的 L-酪氨酸 (Tyr) 可挽救黑色素细胞增殖活性的降低。 L-Tyr 还刺激 TYR 活性、TRP1 和 TRP2 表达以及 IV 期黑素体和色素沉着的成熟。这些结果表明，Mclre 突变影响黑素细胞的增殖和分化，L-Tyr 通过刺激 TYR 活性、TRP1 和 TRP2 表达以及黑素体成熟来挽救增殖和分化活性的降低。

项目成果

Characterization of a new coat color mutant mouse strain showing age-dependent black to brown coat color change.

一种新的毛色突变小鼠品系的表征，显示出年龄依赖性的黑色到棕色毛色变化。

• 发表时间: 2006
• 作者: R. Ishida;E. Inada;S. Tanaka;M. Tamura;H. Masuya;S. Wakana;T. Shiroishi;K. Wakamatsu;S. Ito;H. Yamamoto.
• 通讯作者: H. Yamamoto.

Interaction of Hermansky-Pudlak syndrome genes in the regulation of lysosome-related organelles

• DOI: 10.1111/j.1600-0854.2006.00431.x
• 发表时间: 2006-07-01
• 期刊: TRAFFIC
• 影响因子: 4.5
• 作者: Gautam, Rashi;Novak, Edward K.;Swank, Richard T.
• 通讯作者: Swank, Richard T.

Childhood malnutrution is associated with a reduction in the total melanin content of scalp hair.

儿童营养不良与头皮头发总黑色素含量的减少有关。

• 发表时间: 2007
• 期刊: Br. J. Nutr. 98
• 作者: C. A. McKenzie;K. Wakamutsu;N. A. Hanchard;T. Forrester;S. Ito.
• 通讯作者: S. Ito.

Chzanges of melanosome morphology associated with the differentiation of epidermal melanocytes in slaty mice.

黑素体形态的变化与黑斑小鼠表皮黑素细胞的分化相关。

• 发表时间: 2007
• 期刊: Anat. Rec 290(8)
• 作者: T. Hirobe;H. Abe.
• 通讯作者: H. Abe.

Topical drug rescue strategy and skin protection based on the role of Mclr in UV-induced tanning.

基于 Mclr 在紫外线引起的晒黑中的作用的局部药物救援策略和皮肤保护。

• 发表时间: 2006
• 期刊: Nature 443(21)
• 作者: 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.
• 通讯作者: D. E. Fisher.