Photo-protective effect of sargachromenol against UVB radiationinduced damage through modulating cellular antioxidant systems and apoptosis in human keratinocytes

Abstract

The aim of this study was to evaluate the photochemopreventive effects of sargachromenol(SC)against ultraviolet B(UVB)-induced oxidative stress in human keratinocytes via assessing the antioxidant properties and underlying molecular mechanisms. SC exhibited a significant scavenging effect on UVB-inducedintracellular reactive oxygen species (ROS). SC attenuated UVB-induced oxidative macromolecular damage, including the protein carbonyl content, DNA strand breaks, and 8-isoprostane level. Furthermore, SC decreased UVB-induced Bax, cleaved caspase-9, and cleaved caspase-3 protein levels, but increased that of Bcl-2, which are well-known key mediators of apoptosis.Moreover, SC increased superoxide dismutase, catalase, and heme oxygenase-1 protein expression. Pre-treatment with SC upregulated the total nuclear factor erythroid 2-related factor 2 (Nrf2) levels, which was reduced by UVB irradiation, indicating the involvement of the Nrf2-antioxidant response element signaling pathway. Jun N-terminal kinases (JNK) and extracellular signal-regulated kinase (ERK) are involved in the regulation of many cellular events, including apoptosis. SC treatment reversed JNK and ERK activation induced by UVB. Collectively, these data indicate that SC can provide remarkable cytoprotection against the adverse effects of UVB radiation by modulating cellular antioxidant systems, and suggest the potential of developing a medical agent for ROS-induced skin diseases.

이번 연구에서는 human keratinocytes에서 UVB로 인한 산화적 스트레스에 반대하는 사가 크로메놀의 항산화의 반영과 분자적인 기전을 통한 광화학적 예방 효과를 증명합니다. 사가크로메놀은 UVB로 인한 세포내 ROS 의 효과적인 소거능을 보여주었고, UVB로 인한 산화적인 고분자의 손상, protein carbonyl, DNA 손상과 지질과산화를 낮춰주었고, proapoptotic Bax, cleaved caspase 3 와cleaved caspase 9 의 레벨을 낮춰주었으며 antiapoptotic protein 인 Bcl-2의 레벨을 올려주었습니다. 게다가 사가크로메놀은 UVB로 인해 감소된 superoxide dismutase, catalase, heme oxyganase-1 그리고 Nrf2 의 레벨을 올려주었고, UVB로 인해서 증가된 JNK 와 ERK 의 레벨을 낮춰 주었습니다. 이번 실험결과에서는 사가크로메놀이 ROS로 인한 피부질환 의 약제개발의 가능성을 보여주고, 세포의 항산화시스템에 영향을 주는 UVB 조사의 부정적 효과에 반대하여 세포보호 를 할수 있음을 보여줍니다.