title: Prevention of UV radiation-induced premature skin aging in hairless mice by the novel compound Melanocin A.
abstract: Repetitive exposure of the skin to UV radiation induces various harmful changes, such as thickening, wrinkle formation, inflammation and carcinogenesis. A variety of natural compounds and synthetic compounds have been studied to determine whether they can prevent UV-induced harmful effects. In this study, we investigated the effect of a novel compound, Melanocin A, which was isolated from Eupenicillium shearii F80695, on UV-induced premature skin aging. First, we studied the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9 expression in an immortalized human keratinocyte cell line, HaCaT, in vitro. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and Melanocin A suppressed this expression in a dose-dependent manner. We then investigated the effect of Melanocin A on UV-induced skin changes in hairless mice in vivo. Chronic exposure of hairless mouse dorsal skin to UV increased skin thickness and induced wrinkle formation and the gelatinase activities of MMP-2 and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic skin changes and MMP-2 and MMP-9 expression. Taken together, these results show that Melanocin A can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that Melanocin A should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging.
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Chi-Hyun
authors.initials: CH
authors.lastname: Park
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Jong-Pyung
authors.initials: JP
authors.lastname: Kim
authors.forename: Ick Dong
authors.initials: ID
authors.lastname: Yoo
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000818:Animals; D002460:Cell Line; D003486:Cyanides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D032641:Eurotiales / Q000737:chemistry*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D010789:Phototherapy / Q000379:methods; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015595:Skin Aging / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D003486:Cyanides; D011506:Proteins; D012333:RNA, Messenger; C484096:melanocin A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9