Marliolide Derivative Induces Melanosome Degradation via Nrf2/p62-Mediated Autophagy

International Journal of Molecular Sciences

JaeUn Lee¹  WonJun Choi¹  JiYoung Kim²  SangHo Oh²  EunJung Lee²  Cheong-Yong Yun³  Jong-Hyuk Sung³  Nahyun Choi³ 

[1] College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Gyeonggi-do, Korea;Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea;STEMORE Co. Ltd., Incheon 21983, Korea;

关键词: Nrf2;    p62;    autophagy;    melanosome degradation;   

DOI  :  10.3390/ijms22083995

来源: DOAJ

【 摘 要 】

Nuclear factor erythroid 2-related factor 2 (Nrf2), which is linked to autophagy regulation and melanogenesis regulation, is activated by marliolide. In this study, we investigated the effect of a marliolide derivative on melanosome degradation through the autophagy pathway. The effect of the marliolide derivative on melanosome degradation was investigated in α-melanocyte stimulating hormone (α-MSH)-treated melanocytes, melanosome-incorporated keratinocyte, and ultraviolet (UV)B-exposed HRM-2 mice (melanin-possessing hairless mice). The marliolide derivative, 5-methyl-3-tetradecylidene-dihydro-furan-2-one (DMF02), decreased melanin pigmentation by melanosome degradation in α-MSH-treated melanocytes and melanosome-incorporated keratinocytes, evidenced by premelanosome protein (PMEL) expression, but did not affect melanogenesis-associated proteins. The UVB-induced hyperpigmentation in HRM-2 mice was also reduced by a topical application of DMF02. DMF02 activated Nrf2 and induced autophagy in vivo, evidenced by decreased PMEL in microtubule-associated proteins 1A/1B light chain 3B (LC3)-II-expressed areas. DMF02 also induced melanosome degradation via autophagy in vitro, and DMF02-induced melanosome degradation was recovered by chloroquine (CQ), which is a lysosomal inhibitor. In addition, Nrf2 silencing by siRNA attenuated the DMF02-induced melanosome degradation via the suppression of p62. DMF02 induced melanosome degradation in melanocytes and keratinocytes by regulating autophagy via Nrf2-p62 activation. Therefore, Nrf2 activator could be a promising therapeutic agent for reducing hyperpigmentation.

【 授权许可】

Unknown