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Titolo:
The melanocortin-1 receptor is a key regulator of human cutaneous pigmentation
Autore:
Abdel-Malek, Z; Scott, MC; Suzuki, I; Tada, A; Im, S; Lamoreux, L; Ito, S; Barsh, G; Hearing, VJ;
Indirizzi:
Univ Cincinnati, Dept Dermatol, Cincinnati, OH 45267 USA Univ Cincinnati Cincinnati OH USA 45267 ermatol, Cincinnati, OH 45267 USA POLA Labs, Yokohama, Kanagawa 244, Japan POLA Labs Yokohama Kanagawa Japan 244 Labs, Yokohama, Kanagawa 244, Japan Texas A&M Univ, College Stn, TX 77843 USA Texas A&M Univ College Stn TX USA 77843 M Univ, College Stn, TX 77843 USA Fujita Hlth Univ, Toyoake, Aichi, Japan Fujita Hlth Univ Toyoake Aichi Japan ta Hlth Univ, Toyoake, Aichi, Japan Stanford Univ, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305Stanford Univ, Stanford, CA 94305 USA NCI, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892NCI, Bethesda, MD 20892 USA
Titolo Testata:
PIGMENT CELL RESEARCH
, volume: 13, anno: 2000, supplemento:, 8
pagine: 156 - 162
SICI:
0893-5785(2000)13:<156:TMRIAK>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
MELANOCYTE-STIMULATING-HORMONE; CULTURED HUMAN MELANOCYTES; MOUSE AGOUTI GENE; MOLECULAR-CLONING; RED HAIR; INDUCED MELANOGENESIS; HUMAN KERATINOCYTES; HUMAN EPIDERMIS; ULTRAVIOLET-B; HUMAN HOMOLOG;
Keywords:
melanocortin 1 receptor; human melanocytes; ultraviolet radiation; melanocortins; agouti signaling protein; eumelanin; pheomelanin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
67
Recensione:
Indirizzi per estratti:
Indirizzo: Abdel-Malek, Z Univ Cincinnati, Dept Dermatol, POB 670592, Cincinnati, OH 45267 USA Univ Cincinnati POB 670592 Cincinnati OH USA 45267 5267 USA
Citazione:
Z. Abdel-Malek et al., "The melanocortin-1 receptor is a key regulator of human cutaneous pigmentation", PIGM CELL R, 13, 2000, pp. 156-162

Abstract

The cloning and characterization of the human melanocortin-1 receptor (MC1R) and the demonstration that normal human melanocytes respond to the melanocortins, alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotrophic hormone (ACTH), with increased proliferation and eumelanogenesis had put an end to a long-standing controversy about the role of melanocortins in regulating human cutaneous pigmentation. We have shown that alpha-MSH and ACTH bind the human MC1R with equal affinity, and are equipotent in their mitogenic and melanogenic effects on human melanocytes. We also showed that the activation of the MC1R is important for the melanogenic response ofhuman melanocytes to ultraviolet radiation (UVR). The MC1R is also the principal mediator of the inhibitory effects of agouti signaling protein (ASP)on melanogenesis. Expression of the MC1R is subject to regulation by its own ligands alpha-MSH and ACTH, as well as by UVR and endothelin-1. Recent studies that we conducted on the expression of MC1R variants by human melanocytes and the implications of these variants on the function of the MC1R revealed the following. Human melanocytes homozygous for Arg160Trp mutation in the MC1R demonstrated a significantly reduced response to alpha-MSH. Also, this culture responded poorly to ASP and exhibited an exaggerated cytotoxic response to UVR. Another culture, which was homozygous for Val92Met mutation in the MC1R, demonstrated a normal response to alpha-MSH. Heterozygousmutations that are frequently expressed in various melanocyte cultures didnot disrupt MC1R function. These results begin to elucidate the significance of MC1R variants in the function of the receptor. Our data emphasize thesignificance of a normally functioning MC1R in the response of melanocytesto melanocortins. ASP, and UVR.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/07/20 alle ore 09:01:17