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- Title
Pro-opiomelanocortin-Related Peptides, Prohormone Convertases 1 and 2 and the Regulatory Peptide 7B2 are Present in Melanosomes of Human Melanocytes.
- Authors
Peters, Eva M. J.; Tobin, Desmond J.; Seidah, Nabil G.; Schallreuter, Karin U.
- Abstract
Summary Recently, it has been shown that α-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 α-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 α-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 micro- scopy, and western blotting. For this purpose antibodies against α-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.
- Subjects
PEPTIDES; MELANOCYTES; IMMUNOLOGY
- Publication
Journal of Investigative Dermatology, 2000, Vol 114, Issue 3, p430
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1046/j.1523-1747.2000.00913.x