The role of endothelin-1 in epidermal hyperpigmentation and signaling mechanisms of mitogenesis and melanogenesis.
The paracrine linkage of endothelins (ET) between keratinocytes and melanocytes suggested that ETs are intrinsic mediators for human melanocytes in UVB-induced pigmentation. In this study, the role of ET-1 in the epidermal hyperpigmentation was investigated in vivo and in vitro. The addition of 10 nM ET-1 induced a H-7 (10 microM) suppressible-increase in tyrosinase activity in cultured human melanocytes and was accompanied by elevated levels of tyrosinase and tyrosinase-related protein-1 mRNA expression as shown by Northern blotting. Analysis of signaling mechanisms leading to tyrosinase activation demonstrated the involvements of quick translocation of PKC, the H-7 (10 microM) suppressible-phosphorylation of the threonine residue of several proteins, and highly elevated level of cyclic AMP (4-fold over control). Reverse transcription polymerase chain reaction (RT-PCR) of RNA isolated from the epidermis of human skin exposed to UVB revealed that UVB irradiation with a dose of 2 MED caused a significant increase in the expressions of ET-1, IL-1 alpha, and tyrosinase mRNA signals 5 days after irradiation. The involvement of ET-1 in UVB-pigmentation was also corroborated by the experiments that the extracts of M. Chamomilla, which can act as an antagonist for ET-receptor binding-mediated signaling but has no inhibitory effect on tyrosinase activity in culture, had a significant inhibitory effect on UVB-induced pigmentation in vivo when daily applied immediately after UVB exposure to human skin. These findings suggest that ET-1 is an important mediator in the epidermis for UVB-induced pigmentation in vivo.
Imokawa
G
G
Biological Science Laboratories, Kao Corporation, Tochigi, Japan.
Kobayashi
T
T
Miyagishi
M
M
Higashi
K
K
Yada
Y
Y
D002455:Cell Division; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D004789:Enzyme Activation; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D017495:Hyperpigmentation / Q000209:etiology*; D015603:Keratinocytes / Q000502:physiology / Q000528:radiation effects; D008543:Melanins / Q000096:biosynthesis*; D014442:Monophenol Monooxygenase / Q000096:biosynthesis / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism / Q000528:radiation effects; D017466:Receptors, Endothelin / Q000378:metabolism; D015398:Signal Transduction; D014466:Ultraviolet Rays
D019332:Endothelin-1; D008543:Melanins; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D000242:Cyclic AMP; D014442:Monophenol Monooxygenase; D011493:Protein Kinase C; D019204:GTP-Binding Proteins