title: Heat treatment decreases melanin synthesis via protein phosphatase 2A inactivation.
abstract: In the present study, we investigated the effects of heat treatment on melanogenesis in a mouse melanocyte cell line (Mel-Ab). It has been reported that activated extracellular signal-regulated kinase (ERK) is responsible for microphthalmia-associated transcription factor (MITF) degradation, which leads to a reduction in tyrosinase protein production and melanin synthesis. Here we demonstrate that heat treatment induces sustained ERK activation, which may inhibit melanogenesis. However, the specific ERK pathway inhibitors, PD98059 or U0126 did not restore heat-induced hypopigmentation. Furthermore, PD98059 or U0126 hardly blocked the heat-induced activation of ERK. These results suggest that heat treatment may inactivate protein phosphatase, and thus ERK activation is maintained. To support this hypothesis, we examined the effects of heat treatment on protein phosphatase 2A (PP2A) activity. The results obtained show that heat treatment inactivates PP2A, which may subsequently cause ERK activation and that heat treatment inhibits MITF promoter activity. Overall, our results demonstrate that heat treatment reduces melanin production in a temperature-dependent manner.
authors.affiliation: Research Division for Human Life Sciences, Seoul National University, Korea.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Seo-Hyoung
authors.initials: SH
authors.lastname: Park
authors.forename: Sun-Bang
authors.initials: SB
authors.lastname: Kwon
authors.forename: Sang-Woong
authors.initials: SW
authors.lastname: Youn
authors.forename: Eun-Sang
authors.initials: ES
authors.lastname: Park
authors.forename: Kyoung-Chan
authors.initials: KC
authors.lastname: Park
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006358:Hot Temperature; D008156:Luciferases / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D054648:Protein Phosphatase 2; D013696:Temperature; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
chemical_list: D002070:Butadienes; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D009570:Nitriles; D014157:Transcription Factors; C113580:U 0126; D008156:Luciferases; D014442:Monophenol Monooxygenase; D048049:Extracellular Signal-Regulated MAP Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D010744:Phosphoric Monoester Hydrolases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one