title: Influence of N-glycan processing disruption on tyrosinase and melanin synthesis in HM3KO melanoma cells.
abstract: Tyrosinase, a type I membrane glycoprotein, is synthesized and glycosylated in the endoplasmic reticulum (ER) and Golgi. The enzyme is subsequently transported to melanosomes where it participates in melanogenesis. Previous studies showed that the disruption of early ER N-glycan processing by deoxynojirimycin (DNJ), an inhibitor of alpha-glucosidase, suppresses tyrosinase enzymatic activity and melanogenesis. However, the disruption of late glycan processing, mainly performed by ER and Golgi alpha-1,2-mannosidases, on tyrosinase enzymatic activity and melanogenesis remains to be investigated. Following treatment of HM3KO human melanoma cells with deoxymannojirimycin (DMJ), an inhibitor of alpha-1,2-mannosidase, transport of tyrosinase to the melanosome, enzymatic activity, and melanogenesis were reduced in a dose-dependent manner. However, DMJ did not directly inhibit tyrosinase enzymatic activity and expression. Interestingly, an extract of Streptomyces subrutilus culture medium (ESSCM) containing DMJ and DNJ as the main components inhibited glycosylation and transport of tyrosinase to the melanosome as well as melanin synthesis, but with no negative effects on cell viability. These inhibitory effects of ESSCM were stronger than those of DMJ or DNJ alone. Tyrosinase glycosylation and melanogenesis in HM3KO melanoma cells were more effectively inhibited by DMJ and DNJ combined than DMJ or DNJ alone. Accordingly, we propose that ESSCM is a potential candidate for treating undesirable hyperpigmentation conditions, such as melasma, postinflammatory melanoderma, and solar lentigo.
authors.affiliation: Skin Research Institute, R&D Center, Amore-Pacific Corp, Yongin-Si, Gyeonggi-Do, Korea.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Choi
authors.forename: Soomi
authors.initials: S
authors.lastname: Ahn
authors.forename: Huikyoung
authors.initials: H
authors.lastname: Chang
authors.forename: Nam Suk
authors.initials: NS
authors.lastname: Cho
authors.forename: Kyungmi
authors.initials: K
authors.lastname: Joo
authors.forename: Byeong Gon
authors.initials: BG
authors.lastname: Lee
authors.forename: Ihseop
authors.initials: I
authors.lastname: Chang
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Hwang
mesh_terms: D002460:Cell Line; D006031:Glycosylation; D006801:Humans; D008361:Mannosidases / Q000037:antagonists & inhibitors; D008543:Melanins / Q000096:biosynthesis*; D008545:Melanoma / Q000378:metabolism*; D020460:Melanosomes / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D013302:Streptomyces / Q000737:chemistry
chemical_list: D008543:Melanins; D014442:Monophenol Monooxygenase; D008361:Mannosidases; C046090:mannosyl-oligosaccharide 1,2-alpha-mannosidase