Document Detail

Pro-opiomelanocortin-related peptides, prohormone convertases 1 and 2 and the regulatory peptide 7B2 are present in melanosomes of human melanocytes.
MedLine Citation:
PMID:  10692100     Owner:  NLM     Status:  MEDLINE    
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.
E M Peters; D J Tobin; N G Seidah; K U Schallreuter
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  114     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-04-18     Completed Date:  2000-04-18     Revised Date:  2007-06-05    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  430-7     Citation Subset:  IM    
Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, West Yorkshire, UK.
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MeSH Terms
Blotting, Western
Melanocytes / ultrastructure
Melanosomes / chemistry*
Microscopy, Immunoelectron
Nerve Tissue Proteins / analysis*
Neuroendocrine Secretory Protein 7B2
Pituitary Hormones / analysis*
Pro-Opiomelanocortin / analysis*
Proprotein Convertase 2
Subtilisins / analysis*
alpha-MSH / analysis
Reg. No./Substance:
0/Nerve Tissue Proteins; 0/Neuroendocrine Secretory Protein 7B2; 0/Pituitary Hormones; 0/SCG5 protein, human; 581-05-5/alpha-MSH; 66796-54-1/Pro-Opiomelanocortin; EC 3.4.21.-/Subtilisins; EC Convertase 2

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