Byeong Gon Lee

Loss of elastic fibers causes skin wrinkles in sun-damaged human skin

BACKGROUND Although wrinkling is the most obvious sign of aged skin, the detailed pathomechanism of wrinkle development has not been elucidated. OBJECTIVES In this study, we investigated the role of elastic fibers in the formation of skin wrinkles. METHODS Loss of elastic fibers was measured quantitatively in the facial skins of subjects representing seven decades, and then compared with wrinkle severities. We also investigated whether topical retinoic acid treatment to photoaged human skin can restore destroyed elastic fiber, and the correlation between wrinkle improvement with increase in elastic fibers in RA-treated facial skin. RESULTS We found a significant correlation between decreases in the length, width, number and total area of oxytalan fibers and wrinkle severity. Furthermore, we found that topical application of retinoic acid (0.025%) to chronically photodamaged skin regenerated and restored elastic fibers, and that there was a significant positive correlation between the amount of newly regenerated elastic fiber and the wrinkle improvement caused by retinoic acid. CONCLUSIONS Our results provide an objective insight into the role of elastic fibers in skin wrinkle formation by providing a quantitative correlation between changes in oxytalan fibers and the severity of skin wrinkling.

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 α‐glucosidase, suppresses tyrosinase enzymatic activity and melanogenesis. However, the disruption of late glycan processing, mainly performed by ER and Golgi α‐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 α‐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.