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Sphingosylphosphorylcholine-induced ERK activation inhibits melanin synthesis in human melanocytes

Cited 72 time in Web of Science Cited 72 time in Scopus
Authors
Kim, Dong-Seok; Park, Seo-Hyoung; Kwon, Sun-Bang; Park, Eun-Sang; Huh, Chang-Hun; Youn, Sang-Woong; Park, Kyoung-Chan
Issue Date
2006-03-10
Publisher
Wiley-Blackwell
Citation
Pigment Cell Res. 2006 Apr;19(2):146-53.
Keywords
Antioxidants/pharmacologyCells, CulturedDose-Response Relationship, DrugDown-Regulation/drug effects/physiologyEnzyme Activation/drug effects/physiologyExtracellular Signal-Regulated MAP Kinases/metabolismFlavonoids/pharmacologyHumansMAP Kinase Signaling System/*drug effects/physiologyMaleMelanins/*biosynthesisMelanocytes/cytology/*physiologyMicrophthalmia-Associated Transcription Factor/biosynthesisMonophenol Monooxygenase/antagonists & inhibitors/*metabolismPhosphorylcholine/*analogs & derivatives/metabolism/pharmacologyPigmentation/drug effects/*physiologyPyrones/pharmacologyRibosomal Protein S6 Kinases, 90-kDa/metabolismSphingosine/*analogs & derivatives/metabolism/pharmacology
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.
ISSN
0893-5785 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16524430

https://hdl.handle.net/10371/39191
DOI
https://doi.org/10.1111/j.1600-0749.2005.00287.x
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College of Medicine/School of Medicine (의과대학/대학원)Molecular and Genomic Medicine (분자유전체의학전공)Journal Papers (저널논문_분자유전체의학전공)
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