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

Autor: Noelia Diaz-Morales, Sandra López-Domènech, Francesca Iannantuoni, Irene Escribano-Lopez, Celia Bañuls, Susana Rovira-Llopis, Zaida Abad-Jiménez, José Raúl Herance, Milagros Rocha, Victor M. Victor, Aranzazu M. de Marañón
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Mitochondrial ROS
Male
Antioxidant
endocrine system diseases
medicine.medical_treatment
Mitochondrion
Pharmacology
medicine.disease_cause
Antioxidants
Leukocyte-endothelial Interactions
chemistry.chemical_compound
Sirtuin 1
Leukocytes
chemistry.chemical_classification
Membrane Potential
Mitochondrial
Multidisciplinary
Middle Aged
Mitochondria
Up-Regulation
Medicine
Female
medicine.symptom
Oligopeptides
Rolling Flux
Science
Inflammation
Context (language use)
SIRT1 Levels
Article
03 medical and health sciences
medicine
Cell Adhesion
Human Umbilical Vein Endothelial Cells
Humans
Aged
Reactive oxygen species
Transcription Factor RelA
Glutathione
Sirtuins (SIRT1)
Oxidative Stress
030104 developmental biology
chemistry
Diabetes Mellitus
Type 2
Case-Control Studies
Reactive Oxygen Species
Leukocyte Rolling Velocity
Oxidative stress
Zdroj: Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
Scientific Reports
ISSN: 2045-2322
Popis: 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.
Databáze: OpenAIRE
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