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: 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)

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

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)