The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes
[EN]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 dama...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universidad de Salamanca (USAL) |
| Repositorio: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/169700 |
| Acceso en línea: | http://hdl.handle.net/10366/169700 |
| Access Level: | acceso abierto |
| Palabra clave: | Sirtuina 1 (SIRT1) Diabetes tipo 2 Antioxidante mitocondrial (SS-31) Interacción leucocito-endotelio Estrés oxidativo Inflamación Sirtuin 1 (SIRT1) Type 2 diabetes Mitochondrial antioxidant (SS-31) Leukocyte-endothelium interaction Oxidative stress Inflammation Diabetes Mellitus, Type 2 Antioxidants Oxidative Stress Sirtuin 1 Mitochondria 3209 Farmacología 2403 Bioquímica 2411 Fisiología Humana 2411.04 Fisiología Endocrina diabetes mellitus tipo II sirtuina 1 mitocondrias estrés oxidativo antioxidantes |
| Sumario: | [EN]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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