Exposure of human melanocytes to UVB twice and subsequent incubation leads to cellular senescence and senescence-associated pigmentation through the prolonged p53 expression. Issue 3 (June 2018)

• Record Type: Journal Article
• Authors: Choi, Suh-Yeon; Bin, Bum-Ho; Kim, Wanil; Lee, Eunkyung; Lee, Tae Ryong; Cho, Eun-Gyung
• Is Part Of: Journal of dermatological science. Volume 90:Issue 3(2018)
• Page Start: 303
• Page End: 312
• Publication Date: 2018-06
• Subjects: UVR ultraviolet radiation -- UVsen UVB-induced senescence -- SAP senescence-associated pigmentation -- SA-β-Gal senescence-associated β-galactosidase -- TPA tetradecanoyl phorbol acetate -- CT cholera toxin -- pTpT thymine dinucleotides -- HEMn human epidermal melanocyte neonatal -- CDKN1A cyclin dependent kinase inhibitor 1A -- PFTα pifithrin-α -- TYR tyrosinase -- TYRP1 tyrosinase-related protein 1 -- POMC pro-opiomelanocortin -- α-MSH α-melanocyte-stimulating hormone -- KITLG c-KIT ligand -- HGF hepatocyte growth factor; Human melanocytes -- UVB-induced senescence -- Senescence-associated pigmentation -- p53 -- Hyperpigmentation; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2018.02.016
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: An in vitro model for melanocyte senescence using UVB exposure is proposed. The protocol relies on UVB exposure twice and subsequent 2-week cultivation. Melanocyte senescence accompanies hyperpigmentation via prolonged p53 expression. Abstract: Background: Ultraviolet radiation (UVR) is a well-known factor in skin aging and pigmentation, and daily exposure to subcytotoxic doses of UVR might accelerate senescence and senescence-associated phenomena in human melanocytes. Objective: To establish an in vitro melanocyte model to mimic the conditions of repeated exposure to subcytotoxic doses of UVB irradiation and to investigate key factor(s) for melanocyte senescence and senescence-associated phenomena. Methods: Human epidermal melanocytes were exposed twice with 20 mJ/cm 2 UVB over a 24-h interval and subsequently cultivated for 2 weeks. Senescent phenotypes were addressed morphologically, and by measuring the senescence-associated β-galactosidase (SA-β-Gal) activity, cell proliferation capacity with cell cycle analysis, and melanin content. Results: The established protocol successfully induced melanocyte senescence, and senescent melanocytes accompanied hyperpigmentation. Prolonged expression of p53 was responsible for melanocyte senescence and hyperpigmentation, and treatment with the p53-inhibitor pifithrin-α at 2-weeks post-UVB irradiation, but not at 48 h, significantly reduced melanin content along with decreases in tyrosinase levels. Conclusion: Melanocyte senescence model will be useful for studying the long-term effects of UVB irradiation and pigmentation relevant to physiological photoaging, and screening compounds effective for senescence-associated p53-mediated pigmentation.