The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes.
The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes.
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DOI：
10.1038/s41598-018-34251-8
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发表时间：
2018-10-26
影响因子：
4.6
通讯作者：
Victor VM
中科院分区：
文献类型：
--
作者：
Escribano-Lopez I;Diaz-Morales N;Iannantuoni F;Lopez-Domenech S;de Marañon AM;Abad-Jimenez Z;Bañuls C;Rovira-Llopis S;Herance JR;Rocha M;Victor VM
2型糖尿病（T2 D）中的线粒体损伤和心血管疾病（CVD）以及在此背景下开发新的治疗策略越来越受到关注。目前尚不清楚SS-31等靶向抗氧化剂是否能充分保护糖尿病患者免受氧化损伤。我们的目的是评估SS-31是否调节SIRT 1水平并改善T2 D患者的白细胞-内皮细胞相互作用、氧化应激和炎症。在51例T2 D患者和57例对照者中研究了人体测量和代谢参数。在SS-31处理或未处理的白细胞中测量线粒体活性氧（ROS）的产生、线粒体膜电位、谷胱甘肽含量、白细胞-内皮细胞相互作用、NFκB-p65、TNFα和SIRT 1水平。我们观察到增加的线粒体ROS产生，通过SS-31处理恢复。SS-31还增加了T2 D患者的线粒体膜电位、谷胱甘肽含量、SIRT 1水平和白细胞滚动速度，并降低了滚动流量和粘附。SS-31治疗还降低了糖尿病患者中增强的NFκB-p65和TNFα。我们的研究结果表明，SS-31通过降低氧化应激、白细胞-内皮细胞相互作用、NFκB和TNFα以及增加SIRT 1水平对T2 D患者的白细胞产生有益作用。这些行动支持其作为对抗CVD风险的潜在药物的用途。
There is growing focus on mitochondrial impairment and cardiovascular diseases (CVD) in type 2 diabetes (T2D), and the development of novel therapeutic strategies in this context. It is unknown whether mitochondrial-targeting antioxidants such as SS-31 protect sufficiently against oxidative damage in diabetes. We aimed to evaluate if SS-31 modulates SIRT1 levels and ameliorates leukocyte-endothelium interactions, oxidative stress and inflammation in T2D patients. Anthropometric and metabolic parameters were studied in 51 T2D patients and 57 controls. Production of mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential, glutathione content, leukocyte-endothelium interactions, NFκB-p65, TNFα and SIRT1 levels was measured in leukocytes treated or not with SS-31. We observed increased mitochondrial ROS production that was restored by SS-31 treatment. SS-31 also increased mitochondrial membrane potential, glutathione content, SIRT1 levels and leukocyte rolling velocity and reduced rolling flux and adhesion in T2D patients. NFκB-p65 and TNFα, which were enhanced in diabetic patients, were also reduced by SS-31 treatment. Our results reveal that SS-31 exerts beneficial effects on the leukocytes of T2D patients by reducing oxidative stress, leukocyte-endothelium interactions, NFκB and TNFα and by increasing SIRT1 levels. These actions support its use as a potential agent against CVD risk.
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影响因子：
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作者：
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通讯作者：
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