title: Menadione (Vitamin K3) decreases melanin synthesis through ERK activation in Mel-Ab cells.
abstract: Menadione is a synthetic vitamin K3 derivative. Here, we examined the effects of menadione on melanogenesis and its related signaling pathways. Our results showed that melanin content was significantly reduced after menadione treatment in a dose-dependent manner. However, menadione treatment did not reduce tyrosinase activity directly. Wnt signaling is known to play a major role in the control of melanin synthesis. Thus, we tested the effects of menadione treatment on GSK3β and β-catenin signaling, but found that menadione did not influence either of these signaling pathways. We also investigated changes in the phosphorylation of ERK, which is related to melanin regulation. These results indicated that menadione treatment led to the phosphorylation of ERK. Additionally, menadione treatment reduced both MITF and tyrosinase protein levels. Treatment with PD98059, a specific ERK pathway inhibitor, restored menadione-induced melanin reduction and also prevented MITF and tyrosinase downregulation by menadione. These results suggest that the hypopigmentary action of menadione is due to MITF and tyrosinase downregulation by ERK activation.
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Eun-Hyun
authors.initials: EH
authors.lastname: Kim
authors.forename: Myo-Kyoung
authors.initials: MK
authors.lastname: Kim
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; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017496:Hypopigmentation / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008543:Melanins / Q000096:biosynthesis*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D024483:Vitamin K 3 / Q000494:pharmacology*
chemical_list: D005419:Flavonoids; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D024483:Vitamin K 3; D014442:Monophenol Monooxygenase; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: ERK; GSK3β; MITF; Melanogenesis; Menadione; PVDF; TRP; Tyrosinase; UV; extracellular signal-regulated kinase; glycogen synthase kinase 3β; microphthalmia-associated transcription factor; polyvinylidene fluoride; tyrosinase-related protein; ultraviolet