Effects of lysophosphatidic acid on melanogenesis.
In this study, we investigated the effects of lysophosphatidic acid (LPA) on melanogenesis in Mel-Ab cells. We found that LPA significantly attenuates melanin synthesis, and reduces the activity of tyrosinase, the rate-limiting melanogenic enzyme. Interestingly, LPA was also found to induce the activation of a 90 kDa ribosomal S6 kinase (RSK-1), which is known to phosphorylate microphthalmia-associated transcription factor (MITF) at serine 409. Though it has been previously reported that the phosphorylation of MITF is followed by the degradation of MITF, we found that LPA significantly inhibited MITF promoter activity, and that this reduced MITF and tyrosinase protein production. Our results indicate that LPA contributes to reduced melanin synthesis via the down-regulation of MITF.
Kim
Dong-Seok
DS
Research Division for Human Life Sciences, Seoul National University, Seoul, South Korea.
Park
Seo-Hyoung
SH
Kwon
Sun-Bang
SB
Youn
Sang-Woong
SW
Park
Kyoung-Chan
KC
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D008246:Lysophospholipids / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D019893:Ribosomal Protein S6 Kinases / Q000187:drug effects / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D008246:Lysophospholipids; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D014157:Transcription Factors; D012694:Serine; D014442:Monophenol Monooxygenase; D019893:Ribosomal Protein S6 Kinases; C032881:lysophosphatidic acid