Molecular biology of the target signal for melanogenesis associated genes and vitiligo pathogenesis.

黑素生成相关基因和白癜风发病机制的目标信号的分子生物学。

• 批准号: 08407022
• 负责人: JIMBOW Kowichi
• 金额: $ 21.38万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08407022/
• 关键词: melanin; melanocyte; vitiligo; apoptosis; lysosome; 尋常性白班; 遺伝子導入

This project has studied the biogenesis of melanosomes and function of melanin pigmentation in man for better understanding of the mechanism of leukoderma (e.g., vitiligo). Specifically we have utilized various molecular biology techniques including cDNA transfection of human tyrosinase and tyrosinase-related protein (TRP-1). We have characterized (1) correct assembly and folding of tyrosinase-gene family proteins with the help of calnexin, (2) target signals of tyrosinase-gene family proteins from TGN to melanosomes, (3) functional interactionbetween tyrosinase and lysosome-associated membrane protein in melanosome biogenesis, (4) mechanism of abnormal melanin synthesis in vitiligo melanocytes and (5) chemical modification of melanin precursor and development of depigmentation. The obtained results will be useful not only for better understanding of vitiligo pathogenesis but also for development of new selective melanocytotoxic agents

该项目研究了人类黑素体的生物发生和黑色素沉着的功能，以更好地了解白斑病（例如白癜风）的机制。具体来说，我们利用了各种分子生物学技术，包括人酪氨酸酶和酪氨酸酶相关蛋白（TRP-1）的cDNA转染。我们已经表征了（1）在钙连接蛋白的帮助下酪氨酸酶基因家族蛋白的正确组装和折叠，（2）从TGN到黑素体的酪氨酸酶基因家族蛋白的靶信号，（3）黑素体生物发生中酪氨酸酶和溶酶体相关膜蛋白之间的功能相互作用，（4）白癜风中异常黑色素合成的机制 黑素细胞和（5）黑色素前体的化学修饰和脱色的发展。获得的结果不仅有助于更好地了解白癜风发病机制，而且有助于开发新的选择性黑素细胞毒剂

项目成果

Singh MV et al: "Expression of human tyrosinase in rat glioma cells for brain tumor therapy." Melanoma Res. (印刷中)

Singh MV 等人：“用于脑肿瘤治疗的大鼠神经胶质瘤细胞中的人酪氨酸酶表达”（正在出版）。

Kondo S: "Basement membrane is not a barrier for cytokine permeability" J.Cell Physiol. 171. 190-195 (1997)

Kondo S：“基底膜不是细胞因子渗透性的屏障”J.Cell Physiol。

Minamitsuji Y et al: "Sulphur containing tyrosine analogs can cause selective melano cytotoxicity involving tyrosinase-mediated appoptosis." J Invest Dermatol. (印刷中)

Minamitsuji Y 等人：“含硫的酪氨酸类似物可引起选择性黑素细胞毒性，涉及酪氨酸酶介导的细胞凋亡。”

Kondo S: "Modulation of TGF-β1 production from human keratinocytes by UVB," Exp Dermatol. 6. 105-110 (1997)

Kondo S：“UVB 对人角质形成细胞产生 TGF-β1 的调节”，Exp Dermatol，6. 105-110 (1997)。

Tandon M et al: "Synthesis of the melanogenesis-based antimelanoma agent, N-propionyl-4-S-cysteaminylphenol, and screening of depigmenting and anti-tumor effects" Bio Pharmacol. 55. 2023-2029 (1998)

Tandon M 等人：“基于黑色素生成的抗黑色素瘤药物 N-丙酰基-4-S-半胱氨基苯酚的合成，以及脱色和抗肿瘤作用的筛选”Bio Pharmacol。