Sim Hyunchae, Lee Wonhwa, Choo Samyeol, Park Eui Kyun, Baek Moon-Chang, Lee In-Kyu, Park Dong Ho, Bae Jong-Sup
College of Pharmacy, Kyungpook National University, Daegu, South Korea.
Department of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University, Daegu, South Korea.
Front Med (Lausanne). 2021 Jun 17;8:685032. doi: 10.3389/fmed.2021.685032. eCollection 2021.
Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, and oxidative damage to retinal pigment epithelial (RPE) cells plays a major role in the pathogenesis of AMD. Exposure to high levels of atmospheric particulate matter (PM) with an aerodynamic diameter of <2.5 μm (PM) causes respiratory injury, primarily due to oxidative stress. Recently, a large community-based cohort study in the UK reported a positive correlation between PM exposure and AMD. Sulforaphane (SFN), a natural isothiocyanate found in cruciferous vegetables, has known antioxidant effects. However, the protective effects of SNF in the eye, especially in the context of AMD, have not been evaluated. In the present study, we evaluated the effect of SFN against PM-induced toxicity in human RPE cells (ARPE-19) and elucidated the molecular mechanism of action. Exposure to PM decreased cell viability in ARPE-19 cells in a time- and dose-dependent manner, potentially due to elevated intracellular reactive oxygen species (ROS). SFN treatment increased ARPE-19 cell viability and decreased PM-induced oxidative stress in a dose-dependent manner. PM-induced downregulation of serum- and glucocorticoid-inducible kinase 1 (SGK1), a cell survival factor, was recovered by SFN. PM treatment decreased the enzymatic activities of the antioxidant enzymes including superoxide dismutase and catalase, which were restored by SFN treatment. Taken together, these findings suggest that SFN effectively alleviates PM-induced oxidative damage in human ARPE-19 cells via its antioxidant effects, and that SFN can potentially be used as a therapeutic agent for AMD, particularly in cases related to PM exposure.
年龄相关性黄斑变性（AMD）是老年人失明的主要原因，视网膜色素上皮（RPE）细胞的氧化损伤在AMD发病机制中起主要作用。暴露于空气动力学直径<2.5μm的高浓度大气颗粒物（PM）会导致呼吸损伤，主要是由于氧化应激。最近，英国一项基于社区的大型队列研究报告了PM暴露与AMD之间存在正相关。萝卜硫素（SFN）是十字花科蔬菜中发现的一种天然异硫氰酸盐，具有已知的抗氧化作用。然而，SNF对眼睛的保护作用，尤其是在AMD背景下，尚未得到评估。在本研究中，我们评估了SFN对人RPE细胞（ARPE-19）中PM诱导的毒性的影响，并阐明了其分子作用机制。暴露于PM以时间和剂量依赖性方式降低了ARPE-19细胞的活力，这可能是由于细胞内活性氧（ROS）升高所致。SFN处理以剂量依赖性方式增加了ARPE-19细胞的活力并降低了PM诱导的氧化应激。SFN恢复了PM诱导的细胞存活因子血清和糖皮质激素诱导激酶1（SGK1）的下调。PM处理降低了包括超氧化物歧化酶和过氧化氢酶在内的抗氧化酶的酶活性，而SFN处理可恢复这些酶活性。综上所述，这些发现表明SFN通过其抗氧化作用有效减轻了PM对人ARPE-19细胞的氧化损伤，并且SFN有可能用作AMD的治疗剂，特别是在与PM暴露相关的病例中。
