title: Sphingosylphosphorylcholine-induced ERK activation inhibits melanin synthesis in human melanocytes.
abstract: Sphingosylphosphorylcholine (SPC) is emerging as a potent signaling-lipid mediator. In this study, we investigated the effects of SPC on melanogenesis using cultured human melanocytes. Our results show that SPC significantly inhibits melanin synthesis in a concentration-dependent manner, and further that it reduces the activity of tyrosinase, the rate-limiting melanogenic enzyme. SPC treatment was also found to induce short-thick dendrites in human melanocytes, but not to reduce tyrosinase activity in a cell-free system, whereas kojic acid directly inhibited tyrosinase. These results suggest that SPC reduces pigmentation by indirectly regulating tyrosinase. In further experiments, SPC was found to downregulate microphthalmia-associated transcription factor (MITF) and tyrosinase, and Western blotting showed that SPC induces the activations of extracellular signal-regulated kinase (ERK) and 90 kDa ribosomal S6 kinase (RSK-1). Moreover, the specific ERK pathway inhibitor, PD98059, blocked the hypopigmentation effect of SPC, and abrogated the SPC-mediated downregulation of MITF. These results suggest that the ERK pathway is involved in the melanogenic signaling cascade, and that ERK activation by SPC reduces melanin synthesis via MITF downregulation.
authors.affiliation: Research Division for Human Life Sciences, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, South Korea.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Seo-Hyoung
authors.initials: SH
authors.lastname: Park
authors.forename: Sun-Bang
authors.initials: SB
authors.lastname: Kwon
authors.forename: Eun-Sang
authors.initials: ES
authors.lastname: Park
authors.forename: Chang-Hun
authors.initials: CH
authors.lastname: Huh
authors.forename: Sang-Woong
authors.initials: SW
authors.lastname: Youn
authors.forename: Kyoung-Chan
authors.initials: KC
authors.lastname: Park
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000166:cytology / Q000502:physiology*; D051739:Microphthalmia-Associated Transcription Factor / Q000096:biosynthesis; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010858:Pigmentation / Q000187:drug effects / Q000502:physiology*; D011753:Pyrones / Q000494:pharmacology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D005419:Flavonoids; C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D011753:Pyrones; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; C011890:kojic acid; D014442:Monophenol Monooxygenase; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D013110:Sphingosine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one