title: ARP101 inhibits α-MSH-stimulated melanogenesis by regulation of autophagy in melanocytes.
abstract: Autophagy is a cooperative process between autophagosomes and lysosomes that degrades cellular organelles. Although autophagy regulates the turnover of cellular components, its role in melanogenesis is not clearly established. Previously, we reported that ARP101 induces autophagy in various cancer cells. Here, we show that ARP101 inhibits melanogenesis by regulation of autophagy. ARP101 inhibited α-MSH-stimulated melanin synthesis and suppressed the expression of tyrosinase and TRP1 in immortalized mouse melanocytes. ARP101 also induced autophagy in melanocytes. Knockdown of ATG5 reduced both anti-melanogenic activity and autophagy mediated by ARP101 in α-MSH treated melanocytes. Electron microscopy analysis further revealed that autophagosomes engulf melanin or melanosome in α-MSH and ARP101-treated cells. Collectively, our results suggest that ARP101 inhibits α-MSH-stimulated melanogenesis through the activation of autophagy in melanocytes.
authors.affiliation: Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeoggi-do 446-701, Republic of Korea.
authors.forename: Eun Sung
authors.initials: ES
authors.lastname: Kim
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jo
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Huikyoung
authors.initials: H
authors.lastname: Chang
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Shin
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Choi
authors.forename: Jun Bum
authors.initials: JB
authors.lastname: Kim
authors.forename: Su Hyeon
authors.initials: SH
authors.lastname: Seok
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Jeong Su
authors.initials: JS
authors.lastname: Oh
authors.forename: Myoung-Hwan
authors.initials: MH
authors.lastname: Kim
authors.forename: Eunjoo H
authors.initials: EH
authors.lastname: Lee
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D000071187:Autophagy-Related Protein 5; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: C556450:ARP101 compound; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D013449:Sulfonamides; D000521:alpha-MSH; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase
keywords: ARP101; Autophagy; Melanocytes; Melanogenesis