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Sphingosylphosphorylcholine-induced ERK activation inhibits melanin synthesis in human melanocytes
Cited 78 time in
Web of Science
Cited 80 time in Scopus
- Authors
- Issue Date
- 2006-03-10
- Publisher
- Wiley-Blackwell
- Citation
- Pigment Cell Res. 2006 Apr;19(2):146-53.
- Keywords
- Antioxidants/pharmacology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Down-Regulation/drug effects/physiology ; Enzyme Activation/drug effects/physiology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Flavonoids/pharmacology ; Humans ; MAP Kinase Signaling System/*drug effects/physiology ; Male ; Melanins/*biosynthesis ; Melanocytes/cytology/*physiology ; Microphthalmia-Associated Transcription Factor/biosynthesis ; Monophenol Monooxygenase/antagonists & inhibitors/*metabolism ; Phosphorylcholine/*analogs & derivatives/metabolism/pharmacology ; Pigmentation/drug effects/*physiology ; Pyrones/pharmacology ; Ribosomal Protein S6 Kinases, 90-kDa/metabolism ; Sphingosine/*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
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