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

基本信息

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

项目摘要

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，几乎所有黑色素体都是椭圆形的IV型黑色素体。然而，在Slaty（DCTSLT）黑素细胞中，除了椭圆形的III期黑素体外，还观察到具有纯脂内纤维的椭圆形性III期黑色素体。在片状黑素细胞中，出生后球形黑素体逐渐降低，而椭圆形的黑色素体逐渐增加。 IV期黑素体在斜粒黑素细胞中很少，出生后没有增加。 L-酪氨酸增加了椭圆形的IV型黑色素体，Eumelanin和pheomelanin合成。这些结果表明，SLATY突变阻塞了第三阶段的黑色素体成熟，并影响黑色素体的形态和L-酪氨酸恢复了这些异常。隐性黄色（MCLRE）黑色素细胞在我们的培养系统中主要是Eumelanin产生的。与野生型黑色素细胞相比，隐性黄色黑色素细胞的增殖减少了。黑素细胞的分化也被延迟并抑制了隐性黄色小鼠。酪氨酸酶（Tyr）活性和与Tyr相关的蛋白1（TRP1）和TRP2（Dopachrome互变异酶，DCT）表达降低，此外，抑制了IV期黑素体的成熟。多余的L-酪氨酸（Tyr）添加到培养基中，挽救了黑素细胞增殖活性的减少。 L-TYR还刺激了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突变会影响黑素细胞的增殖和分化，L-TYR通过刺激Tyr Attive，TRP1和TRP2表达以及黑素体成熟来挽救减少的增殖和分化活性。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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。

DOI：
发表时间：
2007
期刊：
Br. J. Nutr. 98
影响因子：
0
作者：
C. A. McKenzie;K. Wakamutsu;N. A. Hanchard;T. Forrester;S. Ito.
通讯作者：
S. Ito.

Gene polymorphism and human pigmentation

基因多态性与人类色素沉着

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
M.H.Brilliant;J.B.Walsh;M.S.Hendersonh;et. al.
通讯作者：
et. al.

A case of partial blond scalp hair : chemical analysis of eumelanin and pheomelanin content.

部分金发病例：真黑素和褐黑素含量的化学分析。

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
K. Tsukamoto;A;Osada;T. Oyama;K. Wakamatsu.
通讯作者：
K. Wakamatsu.

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。

DOI：
发表时间：
2006
期刊：
影响因子：
0
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.