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K+ activating CyPPA inhibits melanogenesis via ERK/MITF pathway
( Tai Kyung Noh ),( Seung Hyun Bang ),( Young Jae Kim ),( Mi Young Jung ),( Hong Il Cho ),( Ik Jun Moon ),( Mi Woo Lee ),( Sung Eun Chang ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2
Background: The development of anti-melanogenesis agents is important for the treatment of hyperpigmentary disorders. In the course of screening for melanogenesis inhibitors in B16F10 cells, we found that CyPPA, a K+ activator, was the strongest anti-melanogenesis agent among HTS library. Objectives: We investigated whether CyPPA would affect melanogenesis in human melanocyte, mouse Mel-Ab cells and MelanoDerm⑩. Methods: Cell viability, melanin contents, tyrosinase(TYR) activity, transcriptional and protein expression levels ofTYR family and other proteins involved in melanogenesis were measured after the treatments of CyPPA. We investigated whether the wnt/モ-catenin, p38 and CREB signaling pathways were involved in the inhibitory effect of CyPPA. The change of ion channel during treatment of CyPPA was also studied. Results: CyPPA treatment significantly decreased the melanin contents, TYR activity and transcriptional and protein expression of TYR family protein and MITF in a concentration-dependent manner. In MelanoDerm⑩, the visual evaluations revealed the significant reduction of melanin content in CyPPA-treated human skin model compared with control-treated ones. CyPPA lowered the content of モ-catenin. Phosphorylated GSK3モdecreased and BIO could reverse the decline of モ-catenin induced by CyPPA. Conclusion: CyPPA is one of the ion channel modulator which regulates melanogenesis and that it may has the potential to be a kind of therapeutic agents forhyperpigmentation.