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

Authors
 Cheong-Yong Yun  ;  Nahyun Choi  ;  Jae Un Lee  ;  Eun Jung Lee  ;  Ji Young Kim  ;  Won Jun Choi  ;  Sang Ho Oh  ;  Jong-Hyuk Sung 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.22(8) : 3995, 2021-04 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Issue Date
2021-04
MeSH
Animals ; Autophagy* / drug effects ; Autophagy* / radiation effects ; Gene Knockdown Techniques ; Humans ; Keratinocytes / drug effects ; Keratinocytes / metabolism ; Keratinocytes / radiation effects ; Lactones / chemistry ; Lactones / pharmacology* ; Male ; Melanins / metabolism ; Melanocytes / drug effects ; Melanocytes / metabolism ; Melanocytes / radiation effects ; Melanoma, Experimental / pathology ; Melanosomes / metabolism* ; Mice ; NF-E2-Related Factor 2 / metabolism* ; Sequestosome-1 Protein / metabolism* ; Skin Pigmentation / drug effects ; Skin Pigmentation / radiation effects ; Ultraviolet Rays
Keywords
Nrf2 ; autophagy ; melanosome degradation ; p62
Abstract
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.
Files in This Item:
T202101872.pdf Download
DOI
10.3390/ijms22083995
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Oh, Sang Ho(오상호) ORCID logo https://orcid.org/0000-0002-4477-1400
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184010
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