Peters E M, Tobin D J, Seidah N G, Schallreuter K U
Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, West Yorkshire, UK.
J Invest Dermatol. 2000 Mar;114(3):430-7. doi: 10.1046/j.1523-1747.2000.00913.x.
Recently, it has been shown that alpha-melanocyte stimulating hormone can directly activate tyrosinase by removing the allosteric regulator 6(R)-L-erythro 5,6,7,8 tetrahydrobiopterin resulting in a stable alpha-melanocyte stimulating hormone/6(R)-L-erythro 5,6,7,8 tetrahydrobiopterin complex. As melanin production occurs in the melanosome, a specific organelle of the melanocyte, it seemed important to investigate whether these organelles themselves actually produce pro-opiomelanocortin-related peptides in their acidic environment. The presence of alpha-melanocyte stimulating hormone and adrenocorticotropin in the epidermis and melanocytes has been shown by several investigators. In order to follow possible pro-opiomelanocortin processing in the melanosome, human melanocytes were established in MCDB 153 medium and utilized for immunohistochemistry, immunogold electron microscopy, and western blotting. For this purpose antibodies against alpha-melanocyte stimulating hormone, adrenocorticotropin, prohormone convertases 1 and 2 (PC1 and PC2) and the PC2 regulatory protein 7B2 were used. Our results demonstrated the presence of the entire system for pro-opiomelanocortin processing in the melanosome. Considering the pH optima of these convertases, the results are in agreement with an autocrine intramelanosomal production of pro- opiomelanocortin-related peptides and an autocrine production and recycling of the cofactor 6(R)-L- erythro 5,6,7,8 tetrahydrobiopterin in melanocytes. Based on these novel observations, we would like to propose that the pigmentation process may not necessarily involve a melanocortin-1 receptor-mediated mechanism.
最近的研究表明，α-黑素细胞刺激素可以通过去除变构调节因子6(R)-L-赤藓糖5,6,7,8-四氢生物蝶呤直接激活酪氨酸酶，从而形成稳定的α-黑素细胞刺激素/6(R)-L-赤藓糖5,6,7,8-四氢生物蝶呤复合物。由于黑色素的产生发生在黑素细胞的特定细胞器黑素小体中，因此研究这些细胞器本身是否真的在其酸性环境中产生促肾上腺皮质激素原相关肽似乎很重要。几位研究者已证实表皮和黑素细胞中存在α-黑素细胞刺激素和促肾上腺皮质激素。为了追踪黑素小体中可能的促肾上腺皮质激素原加工过程，将人黑素细胞置于MCDB 153培养基中培养，并用于免疫组织化学、免疫金电子显微镜和蛋白质印迹分析。为此，使用了针对α-黑素细胞刺激素、促肾上腺皮质激素、激素原转化酶1和2（PC1和PC2）以及PC2调节蛋白7B2的抗体。我们的结果表明黑素小体中存在促肾上腺皮质激素原加工的完整系统。考虑到这些转化酶的最适pH值，结果与黑素细胞中促肾上腺皮质激素原相关肽的自分泌黑素小体内产生以及辅因子6(R)-L-赤藓糖5,6,7,8-四氢生物蝶呤的自分泌产生和循环利用一致。基于这些新的观察结果，我们提出色素沉着过程不一定涉及黑素皮质素-1受体介导的机制。
