Ceramide PC102 inhibits melanin synthesis via proteasomal degradation of microphthalmia-associated transcription factor and tyrosinase

• Published in: Molecular and cellular biochemistry 2013-03, Vol.375 (1-2), p.81-87
• Main Authors: Jeong, Hyo-Soon, Choi, Hye-Ryung, Yun, Hye-Young, Baek, Kwang Jin, Kwon, Nyoun Soo, Park, Kyoung-Chan, Kim, Dong-Seok
• Format: Article
• Language: English
• Subjects: Amides - pharmacology; Animals; beta Catenin - genetics; beta Catenin - metabolism; Biochemistry; Biomedical and Life Sciences; Biosynthesis; Cardiology; Cell cycle; Cell Line; Cell Survival - drug effects; Cosmetics; Cosmetics - pharmacology; Enzymes; Extracellular Signal-Regulated MAP Kinases - metabolism; Fatty acids; Gene Expression - drug effects; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Leupeptins - pharmacology; Life Sciences; Medical Biochemistry; Melanins - biosynthesis; Mice; Microphthalmia-Associated Transcription Factor - metabolism; Monophenol Monooxygenase - genetics; Monophenol Monooxygenase - metabolism; Oncology; Pigments; Propanolamines - pharmacology; Proteasome Endopeptidase Complex - metabolism; Proteasome Inhibitors - pharmacology; Proteolysis; RNA; Signal Transduction; Toy industry
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-012-1530-5

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.