Lee Seung Eun, Kim Gun-Dong, Yang Hana, Son Gun Woo, Park Hye Rim, Cho Jeong-Je, Ahn Hyun-Jong, Park Cheung-Seog, Park Yong Seek
Department of Microbiology, School of Medicine, Kyung Hee University, Seoul, Korea.
J Cardiovasc Pharmacol. 2015 Jul;66(1):108-17. doi: 10.1097/FJC.0000000000000251.
Consumption of omega-3 polyunsaturated fatty acid, particularly eicosapentaenoic acid (EPA), is associated with a significant reduction in the risk of developing cardiovascular disease. The aim of this study was to investigate whether heme oxygenase-1 (HO-1) induction contributes to the cytoprotective effects of EPA in endothelial cells threatened with oxidative damage. In this study, we investigated the effect of EPA on the induction of HO-1 by NF-E2-related factor 2 (Nrf2) in human umbilical vein endothelial cells. In cells treated with low concentrations of EPA (10-25 μM), HO-1 expression increased in a time- and concentration-dependent manner. Additionally, EPA treatment increased Nrf2 nuclear translocation and antioxidant response element activity, leading to the upregulation of HO-1 expression. Furthermore, treatment with EPA reduced hydrogen peroxide (H(2)O(2))-induced cell death. The reduction in cell death was reversed by treatment with zinc protoporphyrin, an inhibitor of HO-1, indicating that HO-1 contributed to the protective effect of EPA. These data suggest that EPA protects against H(2)O(2)-induced oxidative stress in endothelial cells by activating Nrf2 and inducting HO-1 expression.
摄入ω-3多不饱和脂肪酸，尤其是二十碳五烯酸（EPA），与心血管疾病发病风险的显著降低有关。本研究的目的是调查血红素加氧酶-1（HO-1）的诱导是否有助于EPA对受到氧化损伤威胁的内皮细胞的细胞保护作用。在本研究中，我们调查了EPA对人脐静脉内皮细胞中由NF-E2相关因子2（Nrf2）诱导的HO-1的影响。在用低浓度EPA（10 - 25μM）处理的细胞中，HO-1表达呈时间和浓度依赖性增加。此外，EPA处理增加了Nrf2的核转位和抗氧化反应元件活性，导致HO-1表达上调。此外，用EPA处理可减少过氧化氢（H₂O₂）诱导的细胞死亡。用HO-1抑制剂锌原卟啉处理可逆转细胞死亡的减少，表明HO-1有助于EPA的保护作用。这些数据表明，EPA通过激活Nrf2和诱导HO-1表达来保护内皮细胞免受H₂O₂诱导的氧化应激。
