title: Okadaic acid suppresses melanogenesis via proteasomal degradation of tyrosinase.
abstract: Okadaic acid is a C38 fatty acid derivative that is known to specifically inhibit the activity of protein phosphatase 2A (PP2A). Previously, we reported that inhibition of PP2A by okadaic acid elicited extracellular signal-regulated kinase (ERK) activation, and that PP2A may be involved in melanogenesis. However, the effects of okadaic acid on melanogenesis have not been completely evaluated. In the present study, we investigated the molecular mechanisms involved in okadaic acid modulation of melanin synthesis in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment with okadaic acid inhibited melanin production in a dose-dependent manner. Moreover, okadaic acid led to a decrease in tyrosinase protein levels without altering mRNA expression. Therefore, we investigated whether the decreased level of tyrosinase by okadaic acid was related to proteasomal degradation of tyrosinase. We found that MG132, a proteasome inhibitor, almost completely abolished both the downregulation of tyrosinase levels and the inhibition of melanin synthesis by okadaic acid. Taken together, our data indicate that okadaic acid inhibits melanin synthesis via proteasomal degradation of tyrosinase.
authors.affiliation: Department of Biochemistry, Chung-Ang University, College of Medicine.
authors.forename: Hyo-Soon
authors.initials: HS
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; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008544:Melanocytes; D051379:Mice; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D008543:Melanins; D012333:RNA, Messenger; D019319:Okadaic Acid; D014442:Monophenol Monooxygenase; D000071679:Glycogen Synthase Kinase 3 beta; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3; D046988:Proteasome Endopeptidase Complex