S-Space College of Medicine/School of Medicine (의과대학/대학원) Molecular and Genomic Medicine (분자유전체의학전공) Journal Papers (저널논문_분자유전체의학전공)
Sphingosylphosphorylcholine-induced ERK activation inhibits melanin synthesis in human melanocytes
- Kim, Dong-Seok; Park, Seo-Hyoung; Kwon, Sun-Bang; Park, Eun-Sang; Huh, Chang-Hun; Youn, Sang-Woong; Park, Kyoung-Chan
- Issue Date
- Pigment Cell Res. 2006 Apr;19(2):146-53.
- 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
- 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.
- 0893-5785 (Print)
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