| Melanocytes expressing MC1R polymorphisms associated with red hair color have altered MSH-ligand activated pigmentary responses in coculture with keratinocytes. | |
| | |
MedLine Citation:
|
PMID: 17960564 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The occurrence of red hair and pale skin in individuals, which is associated with UV-radiation sensitivity and increased skin cancer risk, is mainly due to polymorphisms in the melanocortin-1 receptor (MC1R) expressed in melanocytes. We have established a serum free human melanocyte-keratinocyte coculture system to study the behavior and functional abilities of melanocytes expressing MC1R red hair color (RHC) variants in order to identify differences from their wild type (WT) counterparts. This model revealed the importance of elevated calcium levels in promoting strong melanocyte interaction with the surrounding keratinocytes and resulted in a dendritic melanocyte morphology similar to that in skin. However, the dendricity response following agonist activation of the MC1R receptor by NDP-MSH peptide, was markedly enhanced in WT melanocytes in comparison to RHC strains. Analysis of mRNA expression and protein levels of the major pigmentation markers following NDP-MSH treatment distinguished the enzyme dopachrome tautomerase as preferentially upregulated in cocultures of WT strains, with negligible or a much reduced response in melanocytes with RHC variant alleles. These results highlight the use of the coculture system in determining fundamental differences in the physiology of melanocytes expressing RHC MC1R receptors and those of WT genotype, which are likely to contribute to the increased skin cancer risk for individuals that carry these variants. |
| | |
Authors:
|
Donald W Roberts; Richard A Newton; J Helen Leonard; Richard A Sturm |
Related Documents
:
|
11601654 - Bmp-2 stimulates tyrosinase gene expression and melanogenesis in differentiated melanoc... 8225244 - Immunohistochemically demonstrated metallothionein expression in malignant melanoma. 9779824 - Hepatocyte growth factor/scatter factor and hepatocytes are potent downregulators of ty... 19937254 - A single uvb exposure increases the expression of functional kit in human melanocytes b... 9323794 - A novel gene (drad-1) expressed in hematopoiesis-supporting stromal cell lines, st2, pa... 11601654 - Bmp-2 stimulates tyrosinase gene expression and melanogenesis in differentiated melanoc... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Journal of cellular physiology Volume: 215 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2008 May |
Date Detail:
|
Created Date: 2008-02-27 Completed Date: 2008-03-25 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: 344-55 Citation Subset: IM |
Copyright Information:
|
(c) 2007 Wiley-Liss, Inc. |
Affiliation:
|
Melanogenix Group, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Biological Markers Calcium / metabolism Cell Differentiation Cells, Cultured Coculture Techniques Dendritic Cells / cytology Hair Color / genetics* Humans Intramolecular Oxidoreductases / genetics, metabolism Keratinocytes / physiology* Ligands Melanocyte-Stimulating Hormones / metabolism* Melanocytes / cytology, drug effects, metabolism, physiology* Osmolar Concentration Polymorphism, Genetic* RNA, Messenger / metabolism Receptor, Melanocortin, Type 1 / genetics*, metabolism* Skin Pigmentation / physiology* Up-Regulation Vimentin / metabolism alpha-MSH / analogs & derivatives, pharmacology |
| Chemical | |
Reg. No./Substance:
|
0/Biological Markers; 0/Ligands; 0/RNA, Messenger; 0/Receptor, Melanocortin, Type 1; 0/Vimentin; 581-05-5/alpha-MSH; 7440-70-2/Calcium; 75921-69-6/MSH, 4-Nle-7-Phe-alpha-; 9002-79-3/Melanocyte-Stimulating Hormones; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.3.12/dopachrome isomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: High-sensitivity analysis of specific peptides in complex samples by selected MS/MS ion monitoring a...
Next Document: Flow-dependent regulation of angiopoietin-2.