title: Involvement of mTOR signaling in sphingosylphosphorylcholine-induced hypopigmentation effects.
abstract: BACKGROUND
  Sphingosylphosphorylcholine (SPC) acts as a potent lipid mediator and signaling molecule in various cell types. In the present study, we investigated the effects of SPC on melanogenesis and SPC-modulated signaling pathways related to melanin synthesis.
  
  
  METHODS
  Melanin production was measured in Mel-Ab cells. A luciferase assay was used to detect transcriptional activity of the MITF promoter. Western blot analysis was performed to examine SPC-induced signaling pathways.
  
  
  RESULTS
  SPC produced significant hypopigmentation effects in a dose-dependent manner. It was found that SPC induced not only activation of Akt but also stimulation of mTOR, a downstream mediator of the Akt signaling pathway. Moreover, SPC decreased the levels of LC3 II, which is known to be regulated by mTOR. Treatment with the mTOR inhibitor rapamycin eliminated decreases in melanin and LC3 II levels by SPC. Furthermore, we found that the Akt inhibitor LY294002 restored SPC-mediated downregulation of LC3 II and inhibited the activation of mTOR by SPC.
  
  
  CONCLUSIONS
  Our data suggest that the mTOR signaling pathway is involved in SPC-modulated melanin synthesis.
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Hyo-Soon
authors.initials: HS
authors.lastname: Jeong
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Yun
authors.forename: Kwang Jin
authors.initials: KJ
authors.lastname: Baek
authors.forename: Nyoun Soo
authors.initials: NS
authors.lastname: Kwon
authors.forename: Kyoung-Chan
authors.initials: KC
authors.lastname: Park
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017496:Hypopigmentation / Q000139:chemically induced / Q000378:metabolism*; D008156:Luciferases; D008543:Melanins / Q000096:biosynthesis*; D051379:Mice; D008858:Microscopy, Phase-Contrast; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014162:Transfection
chemical_list: D002867:Chromones; D008543:Melanins; D009025:Morpholines; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D008156:Luciferases; D014442:Monophenol Monooxygenase; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D013110:Sphingosine; D020123:Sirolimus