Inhibitory effects of N,N,N-trimethyl phytosphingosine-iodide on melanogenesis via ERK activation-mediated MITF degradation

Woo Jin Lee, Seunghyun Bang, Bo Young Chung, Hyejung Jung, Eok Soo Oh, Sung Eun Chang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

N,N,N-trimethyl phytosphingosine-iodide (TMP) was recently developed as an antitumor agent. We examined the effects of TMP on melanogenesis and its related signaling pathways in normal human melanocytes. Our results showed that melanin is significantly reduced in a dose-dependent manner in both cells following liposomal TMP treatment. We also investigated changes in the phosphorylation of extracellular signal-regulated kinase (ERK), which is related to the degradation of microphthalmiaassociated transcription factor (MITF). Our results indicated that liposomal TMP treatment leads to the phosphorylation of ERK, which reduces both MITF and tyrosinase protein levels. Treatment with PD98059, an ERK pathway-specific inhibitor, restored liposomal TMP-induced reductions in melanin, abrogated reductions in tyrosinase activity, and downregulated MITF and tyrosinase protein. In conclusion, these results suggest that the inhibitory effects of TMP on melanogenesis are due to MITF and tyrosinase downregulation via ERK activation.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
JournalBioscience, Biotechnology and Biochemistry
Volume80
Issue number1
DOIs
StatePublished - 2016

Keywords

  • Extracellular signal-regulated kinase
  • Melanogenesis
  • Microphthalmia-associated transcription factor
  • Phytosphingosine

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