Endothelin-1 is a paracrine growth factor that modulates melanogenesis of human melanocytes and participates in their responses to ultraviolet radiation.
Endothelin (ET)-1, alpha-melanocyte stimulating hormone (alpha-melanotropin; alpha-MSH), and basic fibroblast growth factor (bFGF) are keratinocyte-derived factors that interact synergistically to stimulate human melanocyte proliferation. ET-1 has a dose-dependent mitogenic effect on human melanocytes and a biphasic effect on melanogenesis: a stimulatory effect at subnanomolar concentrations, and an inhibitory effect at concentrations equal to or higher than 1 nM. Human melanocytes express ET B receptors. Brief treatment of melanocytes with ET-1 caused up-regulation of alpha-MSH receptor mRNA but did not alter ET B receptor mRNA level. ET-1 modulates the response of human melanocytes to UV rays (UVRs). Treatment of melanocytes with 10 nM ET-1 immediately after exposure to UVRs enabled them to overcome the G1 growth arrest. However, ET-1 did not inhibit p53 accumulation or p21(Waf-1/SDI-1/Cip-1) overexpression, nor did it reverse the hypophosphorylated state of pRb or the reduction in Bcl2 level in irradiated melanocytes. These results substantiate the role of ET-1 as a paracrine regulator that modulates the response of human melanocytes to UVRs.
POLA Laboratories, Yokohama, Japan.
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A
Tada
I
I
Suzuki
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S
Im
M B
MB
Davis
J
J
Cornelius
G
G
Babcock
J J
JJ
Nordlund
Z A
ZA
Abdel-Malek
D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000502:physiology*; D019334:Endothelin-3 / Q000502:physiology; D005786:Gene Expression Regulation; D019254:Genes, bcl-2 / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008544:Melanocytes / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D008934:Mitogens / Q000502:physiology; D019899:Paracrine Communication; D011836:Radiation Tolerance; D044023:Receptor, Endothelin B; D018043:Receptors, Corticotropin / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism; D044101:Receptors, Melanocortin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014466:Ultraviolet Rays; D000521:alpha-MSH / Q000502:physiology
D019332:Endothelin-1; D019334:Endothelin-3; D008934:Mitogens; D044023:Receptor, Endothelin B; D018043:Receptors, Corticotropin; D017466:Receptors, Endothelin; D044101:Receptors, Melanocortin; D016159:Tumor Suppressor Protein p53; D000521:alpha-MSH