中药单体促黑素合成作用及毛囊外根鞘无色素性黑素细胞激活和移行的研究
摘要
黑素细胞是表皮中树突状细胞的一种,来源于神经嵴。黑素细胞的主要功能就是合成黑素,不同个体皮肤颜色的差异主要是由于黑素细胞合成黑素的种类和数量不同而造成的。黑素可分为两种:棕/黑色的优黑素和黄/红色的褐黑素。人类皮肤着色包括结构性和功能性两类:结构性着色由遗传决定,不受外界环境的影响。功能性着色是环境作用下的黑素合成基础水平的增加。
合成黑素是黑素细胞最重要的功能及分化特征,黑素合成是一个多步骤的酶促生化反应,有着复杂的而精确的调控。现已知有如下9个环节参与了黑素合成的调控。
1.黑素母细胞由神经嵴向表皮、毛囊等处迁移;
2.黑素细胞定植表皮等处后的局部克隆;
3.黑素细胞中编码黑素合成相关酶和黑素小体基质蛋白基因转录;
4.4个酪氨酸酶家族成员及酪氨酸酶(TYR)、酪氨酸酶相关蛋白-1(TRP-1)、酪氨酸酶相关蛋白-2(TRP-2)和stablin蛋白的翻译;
5.酪氨酸酶翻译后加工和糖基化;
6.黑素细胞中的囊泡融合形成黑素小体,成熟的酪氨酸酶转运进入
Melanocyte, possessing the specialized cytoplasmic organization and the biosynthetic apparatus to generate melanin, is a kind of dendritic cell derived from neural crest. The quantity and quality of melanin are the main determination of skin color. Melanin may be either brown-black (eumelanin) or yellow-red (pheomelanin), whose pigmentation in human skin can be divided into constitutive and facultative skin colors. Constitutive, or intrinsic, skin color is a genetically determined degree of cutaneous melanin pigmentation, which is present independent of outside influences. Facultative skin color represents the increased melanin pigmentation above that of the constitutive level; and other environmental factors upon the individual's genetically endowed melanogenic potential.Production of melanin is one of the most well known differentication features of melanocytes, which is a process consistes of many steps of biochemical enzyme-catalyzed reactions and is regulated complicated and precised. The process of the melanogenesis may be summarized in nine
stages difined as follows:(1)Migration of pigment cell precursors from the neural crest. (2)Clonal population of skin by melanocytes. (3)Induction of melanogenic genes, including tyrosinase, tyrosinase related protein and melanosomal matrix components. (4)Synthesis of tyrosinase and related melanogenic proteins. (5)Posttranslational processing and glycosylation of tyrosinase. (6)Fusion of vesicles to form melanosomes and initiation of melanogenesis. (7)Control of tyrosinase activity and activity of tyosinase related proteins. (8)Posttyrosinase modification of biosythesis. (9)Modification of melanin. Hypopigmentation or hyperpigmentation may arise from interference with any of these processes. To updata, the investigation about melanogenesis almost developed underneath synthesis of tyrosinase and related mlanogenic proteins. Tyrosinase activity is a key determinant of melanin production in the skin. This enzyme catalysis the early rate-limiting steps of the biosynthetic pathway of melanin: the hydroxylation of tyrosine and the oxidation of dopa. Moreover, the rate of melanin synthesis is correlated with the amount and activity of tyrosinase in the cells. In addition, a positive relationship exists between human skin color and the activity of this enzyme. Melanin production appears to be regulated by a subtle balance between positive (tyrosinase, TRP-1 and TRP-2) and negative (melanogenic inhibitors) melanogenic factors. TRP-1 shares the
two catalytic properties ascribed to tyrosinase. TRP-2 catalyzes the conversion of DOPAchrome to DHICA (5,6-dihydroxyindole-2-carboxylic acid) and seems to play a key role in the control of the distal steps of the melaninpathway synthesis. In our last researchs, we found some Chinese herbs can increase the activity of tyrosinase in vitro. To further study the melanogenesis action and mechanism of those herbs, we applied some nature chemicals from Chinese traditional medicine and observe their roles on Cloudman S91 melanoma cells and melanocytes from human epidermis. We hope to select a safe and most effective nature chemical for the future treatment of pigmented skin disease.Vitiligo is an acquired melanin pigmentary disorder manifesting itself by expanding depigmented lesions of the skin. Pathologically, absence of melanin and melanocytes from affected epidermis and degeneration of melanocytes and basal keratinocytes are observed in patients with vitiligo. Repigmentation of vitiligo is usually seen in a perifollicular manner. During this process it is thought that amelanotic melanocytes of outer root shealth in human hair follicle often act as a reservoir population of melanocytes. It become activates, proliferate and migrate into depigmented epidermis underneath some stimulator such as radiation with ultraviolet A and narrow-band ultraviolet B,
psoralen-ultraviolet A, local applying with cortico steroid and tretinoin. However, the pathogenesis is still not known. It has been reported that some cytokins secreted from keratinocytes around
合成黑素是黑素细胞最重要的功能及分化特征,黑素合成是一个多步骤的酶促生化反应,有着复杂的而精确的调控。现已知有如下9个环节参与了黑素合成的调控。
1.黑素母细胞由神经嵴向表皮、毛囊等处迁移;
2.黑素细胞定植表皮等处后的局部克隆;
3.黑素细胞中编码黑素合成相关酶和黑素小体基质蛋白基因转录;
4.4个酪氨酸酶家族成员及酪氨酸酶(TYR)、酪氨酸酶相关蛋白-1(TRP-1)、酪氨酸酶相关蛋白-2(TRP-2)和stablin蛋白的翻译;
5.酪氨酸酶翻译后加工和糖基化;
6.黑素细胞中的囊泡融合形成黑素小体,成熟的酪氨酸酶转运进入
Melanocyte, possessing the specialized cytoplasmic organization and the biosynthetic apparatus to generate melanin, is a kind of dendritic cell derived from neural crest. The quantity and quality of melanin are the main determination of skin color. Melanin may be either brown-black (eumelanin) or yellow-red (pheomelanin), whose pigmentation in human skin can be divided into constitutive and facultative skin colors. Constitutive, or intrinsic, skin color is a genetically determined degree of cutaneous melanin pigmentation, which is present independent of outside influences. Facultative skin color represents the increased melanin pigmentation above that of the constitutive level; and other environmental factors upon the individual's genetically endowed melanogenic potential.Production of melanin is one of the most well known differentication features of melanocytes, which is a process consistes of many steps of biochemical enzyme-catalyzed reactions and is regulated complicated and precised. The process of the melanogenesis may be summarized in nine
stages difined as follows:(1)Migration of pigment cell precursors from the neural crest. (2)Clonal population of skin by melanocytes. (3)Induction of melanogenic genes, including tyrosinase, tyrosinase related protein and melanosomal matrix components. (4)Synthesis of tyrosinase and related melanogenic proteins. (5)Posttranslational processing and glycosylation of tyrosinase. (6)Fusion of vesicles to form melanosomes and initiation of melanogenesis. (7)Control of tyrosinase activity and activity of tyosinase related proteins. (8)Posttyrosinase modification of biosythesis. (9)Modification of melanin. Hypopigmentation or hyperpigmentation may arise from interference with any of these processes. To updata, the investigation about melanogenesis almost developed underneath synthesis of tyrosinase and related mlanogenic proteins. Tyrosinase activity is a key determinant of melanin production in the skin. This enzyme catalysis the early rate-limiting steps of the biosynthetic pathway of melanin: the hydroxylation of tyrosine and the oxidation of dopa. Moreover, the rate of melanin synthesis is correlated with the amount and activity of tyrosinase in the cells. In addition, a positive relationship exists between human skin color and the activity of this enzyme. Melanin production appears to be regulated by a subtle balance between positive (tyrosinase, TRP-1 and TRP-2) and negative (melanogenic inhibitors) melanogenic factors. TRP-1 shares the
two catalytic properties ascribed to tyrosinase. TRP-2 catalyzes the conversion of DOPAchrome to DHICA (5,6-dihydroxyindole-2-carboxylic acid) and seems to play a key role in the control of the distal steps of the melaninpathway synthesis. In our last researchs, we found some Chinese herbs can increase the activity of tyrosinase in vitro. To further study the melanogenesis action and mechanism of those herbs, we applied some nature chemicals from Chinese traditional medicine and observe their roles on Cloudman S91 melanoma cells and melanocytes from human epidermis. We hope to select a safe and most effective nature chemical for the future treatment of pigmented skin disease.Vitiligo is an acquired melanin pigmentary disorder manifesting itself by expanding depigmented lesions of the skin. Pathologically, absence of melanin and melanocytes from affected epidermis and degeneration of melanocytes and basal keratinocytes are observed in patients with vitiligo. Repigmentation of vitiligo is usually seen in a perifollicular manner. During this process it is thought that amelanotic melanocytes of outer root shealth in human hair follicle often act as a reservoir population of melanocytes. It become activates, proliferate and migrate into depigmented epidermis underneath some stimulator such as radiation with ultraviolet A and narrow-band ultraviolet B,
psoralen-ultraviolet A, local applying with cortico steroid and tretinoin. However, the pathogenesis is still not known. It has been reported that some cytokins secreted from keratinocytes around
引文
1 雷铁池,朱文元,夏明玉等89味中药乙醇提取物对酪氨酸酶活性的上调作用。临床皮肤科杂志,1999,28(3):147-149.
2 Ando H, Itoh A, Mishima Y, et al. Correlation between the number of melanosomes, tyrosinase mRNA levels, and tyrosinase activity in cultured murine melanoma cells in response to various melanogenesis regulatory agents. J Cell Physiol, 1995,163:608-614.
3 Lin Z, Hoult JR, Bennett DC, et al. Stimulation of mouse melanocyte proliferation by Piper nigrum fruit extract and its main alkaloid, piperine. Planta Med. 1999;65(7):600-603.
4 Bicamumpaka C, Page M. Paclitaxel stimulates melanogenesis in
2 Ando H, Itoh A, Mishima Y, et al. Correlation between the number of melanosomes, tyrosinase mRNA levels, and tyrosinase activity in cultured murine melanoma cells in response to various melanogenesis regulatory agents. J Cell Physiol, 1995,163:608-614.
3 Lin Z, Hoult JR, Bennett DC, et al. Stimulation of mouse melanocyte proliferation by Piper nigrum fruit extract and its main alkaloid, piperine. Planta Med. 1999;65(7):600-603.
4 Bicamumpaka C, Page M. Paclitaxel stimulates melanogenesis in