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.
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Authors | Dong-Seok Kim, Seo-Hyoung Park, Sun-Bang Kwon, Eun-Sang Park, Chang-Hun Huh, Sang-Woong Youn, Kyoung-Chan Park |
Journal | Pigment cell research
(Pigment Cell Res)
Vol. 19
Issue 2
Pg. 146-53
(Apr 2006)
ISSN: 0893-5785 [Print] Denmark |
PMID | 16524430
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antioxidants
- Flavonoids
- MITF protein, human
- Melanins
- Microphthalmia-Associated Transcription Factor
- Pyrones
- sphingosine phosphorylcholine
- Phosphorylcholine
- kojic acid
- Monophenol Monooxygenase
- RPS6KA1 protein, human
- Ribosomal Protein S6 Kinases, 90-kDa
- Extracellular Signal-Regulated MAP Kinases
- Sphingosine
- 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Topics |
- 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)
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