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首页> 外文期刊>Journal of Cellular Physiology >Tetrahydrocurcumin ameliorates homocysteine‐mediated mitochondrial remodeling in brain endothelial cells
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Tetrahydrocurcumin ameliorates homocysteine‐mediated mitochondrial remodeling in brain endothelial cells

机译:Tetrahydrocurcumin改善了同型半胱氨酸检测线粒体介导的重构大脑内皮细胞

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Homocysteine (Hcy) causes endothelial dysfunction by inducing oxidative stress in most neurodegenerative disorders. This dysfunction is highly correlated with mitochondrial dynamics such as fusion and fission. However, there are no strategies to prevent Hcy‐induced mitochondrial remodeling. Tetrahydrocurcumin (THC) is an anti‐inflammatory and anti‐oxidant compound. We hypothesized that THC may ameliorates Hcy‐induced mitochondria remodeling in mouse brain endothelial cells (bEnd3) cells. bEnd3 cells were exposed to Hcy treatment in the presence or absence of THC. Cell viability and autophagic cell death were measured with MTT and MDC staining assay. Reactive oxygen species (ROS) production was determined using DCFH‐DA staining by confocal microscopy. Autophagy flux was assessed using a conventional GFP‐microtubule‐associated protein 1 light chain 3 (LC3) dot assay. Interaction of phagophore marker LC‐3 with mitochondrial receptor NIX was observed by confocal imaging. Mitochondrial fusion and fission were evaluated by western blot and RT‐PCR. Our results demonstrated that Hcy resulted in cell toxicity in a dose‐dependent manner and supplementation of THC prevented the detrimental effects of Hcy on cell survival. Furthermore, Hcy also upregulated fission marker (DRP‐1), fusion marker (Mfn2), and autophagy marker (LC‐3). Finally, we observed that Hcy activated mitochondrial specific phagophore marker (LC‐3) and co‐localized with the mitochondrial receptor NIX, as viewed by confocal microscopy. Pretreatment of bEnd3 with THC (15?μM) ameliorated Hcy‐induced oxidative damage, mitochondrial fission/fusion, and mitophagy. Our studies strongly suggest that THC has beneficial effects on mitochondrial remodeling and could be developed as a potential therapeutic agent against hyperhomocysteinemia (HHcy) induced mitochondrial dysfunction.
机译:同型半胱氨酸(Hcy)导致内皮功能障碍大多数诱导氧化应激神经退行性疾病。与线粒体动力学高度相关如聚变和裂变。策略,以防止Hcy诱导线粒体重构。抗炎症和抗氧化剂复合。假设THC可能改善Hcy的诱导线粒体在老鼠大脑重塑内皮细胞(bEnd3)细胞。存在或暴露于Hcy治疗缺乏THC。细胞死亡与MTT和争取民主变革运动的测量染色试验。生产决定使用DCFH DA染色共焦显微镜。使用传统的评估GFP量微管相关蛋白1轻链3 (LC3)点分析。标记LC 3与线粒体受体无观察到共焦成像。聚变和裂变是评估蛋白质印迹和RT PCR。导致细胞毒性剂量依赖方式和补充的THC阻止了有害的Hcy对细胞存活率的影响。此外,Hcy还调节裂变的标记(DRP量1),融合标记(进行Mfn2)和自噬地理标志(LC 3)。激活线粒体特定phagophore地理标志(LC 3)和公司的本地化线粒体受体NIX,如被共焦显微镜。(15 ?μM)改善Hcy高诱导氧化损伤线粒体核裂变或核聚变,mitophagy。研究表明,THC有益影响线粒体重构和可能发展为一个潜在的治疗的代理针对半胱氨酸(HHcy)诱导线粒体功能障碍。

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