title: The regulatory mechanism of melanogenesis by FTY720, a sphingolipid analogue.
abstract: We previously reported that sphingosine-1-phosphate (S1P) decreases melanin synthesis via extracellular signal-regulated protein kinase (ERK) activation and microphthalmia-associated transcription factor (MITF) degradation. Although FTY720 is an S1P structural analogue, the effects of FTY720 on melanogenesis are not completely understood. Thus, we investigated the influence of FTY720 on melanin synthesis in a spontaneously immortalized mouse melanocyte cell line (Mel-Ab). FTY720 inhibited melanin synthesis in a concentration-dependent manner. Further, FTY720 has a different signal transduction mechanism to regulate melanogenesis from the S1P-induced signalling pathway. Our results showed that FTY720 down-regulated MITF and tyrosinase expression without ERK activation. MITF, the master regulator of pigmentation, is a target for the Wnt signalling pathway, including glycogen synthase kinase 3β (GSK3β) and β-catenin. Thus, the influence of FTY720 on GSK3β and β-catenin was further investigated. Decreased MITF and tyrosinase were associated with a reduction of β-catenin protein and mRNA levels. Decreased β-catenin expression by FTY720 may down-regulate expression of MITF, which finally reduces melanin synthesis.
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Ju Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Yun-Mi
authors.initials: YM
authors.lastname: Jeong
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: D000818:Animals; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000068876:Fingolimod Hydrochloride; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011409:Propylene Glycols / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D007211:Indoles; D008301:Maleimides; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D011409:Propylene Glycols; D047428:Protein Kinase Inhibitors; C417521:SB 216763; D051176:beta Catenin; D014442:Monophenol Monooxygenase; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine