The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes

Abstract 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...

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Autores principales:	Irene Escribano-Lopez, Noelia Diaz-Morales, Francesca Iannantuoni, Sandra Lopez-Domenech, Aranzazu M de Marañon, Zaida Abad-Jimenez, Celia Bañuls, Susana Rovira-Llopis, Jose R Herance, Milagros Rocha, Victor M Victor
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Sirtuins (SIRT1) SIRT1 Levels Leukocyte-endothelial Interactions Leukocyte Rolling Velocity Rolling Flux Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e519efa5e8d480d87d2a3592d56800e
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spelling	oai:doaj.org-article:8e519efa5e8d480d87d2a3592d56800e2021-12-02T15:08:17ZThe mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes10.1038/s41598-018-34251-82045-2322https://doaj.org/article/8e519efa5e8d480d87d2a3592d56800e2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-34251-8https://doaj.org/toc/2045-2322Abstract 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.Irene Escribano-LopezNoelia Diaz-MoralesFrancesca IannantuoniSandra Lopez-DomenechAranzazu M de MarañonZaida Abad-JimenezCelia BañulsSusana Rovira-LlopisJose R HeranceMilagros RochaVictor M VictorNature PortfolioarticleSirtuins (SIRT1)SIRT1 LevelsLeukocyte-endothelial InteractionsLeukocyte Rolling VelocityRolling FluxMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Sirtuins (SIRT1) SIRT1 Levels Leukocyte-endothelial Interactions Leukocyte Rolling Velocity Rolling Flux Medicine R Science Q
spellingShingle	Sirtuins (SIRT1) SIRT1 Levels Leukocyte-endothelial Interactions Leukocyte Rolling Velocity Rolling Flux Medicine R Science Q Irene Escribano-Lopez Noelia Diaz-Morales Francesca Iannantuoni Sandra Lopez-Domenech Aranzazu M de Marañon Zaida Abad-Jimenez Celia Bañuls Susana Rovira-Llopis Jose R Herance Milagros Rocha Victor M Victor The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes
description	Abstract 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.
format	article
author	Irene Escribano-Lopez Noelia Diaz-Morales Francesca Iannantuoni Sandra Lopez-Domenech Aranzazu M de Marañon Zaida Abad-Jimenez Celia Bañuls Susana Rovira-Llopis Jose R Herance Milagros Rocha Victor M Victor
author_facet	Irene Escribano-Lopez Noelia Diaz-Morales Francesca Iannantuoni Sandra Lopez-Domenech Aranzazu M de Marañon Zaida Abad-Jimenez Celia Bañuls Susana Rovira-Llopis Jose R Herance Milagros Rocha Victor M Victor
author_sort	Irene Escribano-Lopez
title	The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes
title_short	The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes
title_full	The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes
title_fullStr	The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes
title_full_unstemmed	The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes
title_sort	mitochondrial antioxidant ss-31 increases sirt1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/8e519efa5e8d480d87d2a3592d56800e
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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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