title: Ceramide PC102 inhibits melanin synthesis via proteasomal degradation of microphthalmia-associated transcription factor and tyrosinase.
abstract: A few types of ceramide are reported to decrease melanin synthesis. In the present study, we examined the effects of an artificial ceramide analog, PC102, on melanogenesis using a spontaneously immortalized melanocyte cell line (Mel-Ab). PC102 is currently used as a moisturizing additive in a variety of cosmetics. Our data showed that PC102 inhibited melanin production and tyrosinase activity in a dose-dependent manner, but did not directly affect tyrosinase activity. Microphthalmia-associated transcription factor (MITF), tyrosinase, and β-catenin protein levels decreased after 48 h of PC102 treatment. In contrast, PC102 did not decrease MITF, tyrosinase, and β-catenin mRNA levels. Therefore, we investigated whether the decrease in MITF and tyrosinase by PC102 is due to proteasomal degradation. MG132, a proteasomal inhibitor, completely abolished tyrosinase downregulation due to PC102 and partially reduced the downregulation of MITF and β-catenin due to PC102. Moreover, MG132 abrogated the inhibition of melanin synthesis by PC102. Taken together, our data suggest that PC102 may inhibit melanin synthesis through MITF and tyrosinase degradation.
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: Hye-Ryung
authors.initials: HR
authors.lastname: Choi
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: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003358:Cosmetics / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007976:Leupeptins / Q000494:pharmacology; D008543:Melanins / Q000096:biosynthesis*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology; D059748:Proteolysis; D015398:Signal Transduction; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C582147:1,3-bis(N-2-(hydroxyethyl)lauroylamino)-2-hydroxypropane; D000577:Amides; D003358:Cosmetics; D007976:Leupeptins; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D011412:Propanolamines; D061988:Proteasome Inhibitors; D051176:beta Catenin; D014442:Monophenol Monooxygenase; D000071679:Glycogen Synthase Kinase 3 beta; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde