title: Sphingosylphosphorylcholine inhibits melanin synthesis via pertussis toxin-sensitive MITF degradation.
abstract: OBJECTIVE
  Sphingolipids act as structural components in cell membranes, and form lipid intermediates that have functional roles as signalling molecules in various cellular processes. Our previous findings have suggested that sphingolipid metabolites are deeply involved in the regulation of melanogenic processes. In this study we aimed to examine sphingosylphosphorylcholine-mediated signalling pathways related to melanogenesis.
  
  
  METHODS
  We determined the hypopigmenting effects and the related signalling pathways of sphingosylphosphorylcholine in Mel-Ab cells. In particular, we analysed the involvement of the G-protein-coupled receptor in sphingosylphosphorylcholine-induced MITF degradation.
  
  
  RESULTS
  Western blotting revealed that sphingosylphosphorylcholine induced the activation of extracellular signal-regulated kinase (ERK), as well as Akt. Moreover, the specific Akt pathway inhibitor LY294002 blocked the hypopigmenting effect of sphingosylphosphorylcholine and abrogated the sphingosylphosphorylcholine-mediated down-regulation of microphthalmia-associated transcription factor (MITF), showing that the Akt pathway is involved in sphingosylphosphorylcholine-mediated melanin inhibition. Treatment with the proteasome inhibitor MG132 blocked the decrease in MITF by sphingosylphosphorylcholine, but sphingosylphosphorylcholine did not decrease the level of MITF mRNA, indicating that the reduction in the level of MITF results from MITF degradation. Furthermore, pre-incubation of Mel-Ab cells with pertussis toxin completely abolished the hypopigmenting effects and the activation of ERK and Akt by sphingosylphosphorylcholine, suggesting that the effects of sphingosylphosphorylcholine are mainly dependent on the G-protein-coupled receptor).
  
  
  CONCLUSIONS
  Together, these results suggest that sphingosylphosphorylcholine reduces melanin synthesis via pertussis toxin-sensitive ERK and Akt activation, and subsequent MITF degradation.
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, Seoul, Republic of Korea. ds_kim@cau.ac.kr
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Seo-Hyoung
authors.initials: SH
authors.lastname: Park
authors.forename: Sun-Bang
authors.initials: SB
authors.lastname: Kwon
authors.forename: Nyoun Soo
authors.initials: NS
authors.lastname: Kwon
authors.forename: Kyoung-Chan
authors.initials: KC
authors.lastname: Park
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D047468:Immunoprecipitation; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D008858:Microscopy, Phase-Contrast; D010766:Phosphorylation; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D043562:Receptors, G-Protein-Coupled; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D013110:Sphingosine