Sphingosylphosphorylcholine‐induced ERK activation inhibits melanin synthesis in human melanocytes
2005; Wiley; Volume: 19; Issue: 2 Linguagem: Inglês
10.1111/j.1600-0749.2005.00287.x
ISSN1600-0749
AutoresDong‐Seok Kim, Seo‐Hyoung Park, Sun‐Bang Kwon, Eun‐Sang Park, Chang‐Hun Huh, Sang Woong Youn, Kyoung‐Chan Park,
Tópico(s)Bioactive natural compounds
ResumoSummary 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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