The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes
Open accessAbstract
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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In type 2 diabetes, animal models and human islet and leukocyte samples provide evidence that elamipretide decreases oxidative stress.
“decreasing oxidative stress291”
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“Furthermore, studies of leukocytes taken from patients with type 2 diabetes, demonstrated a reduction in inflammation, via down regulation of TNF-alpha and NF-kB and upregulation of SIRT1, in response to treatment with SS-31 peptide (Escribano-Lopez et al. 2018).”
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- Authors
- Escribano-Lopez, I., Diaz-Morales, N., Iannantuoni, F., Lopez-Domenech, S., de Marañon, A. M., Abad-Jimenez, Z., Bañuls, C., Rovira-Llopis, S., Herance, J. R., Rocha, M., & Victor, V. M.
- Affiliations
- Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (ES)
- Universitat de València (ES)
- Corresponding author
- Rocha, Milagros
- Venue
- Scientific Reports
- Published
- 2018-10-26
- Volume
- 8
- Issue
- 1
- Pages
- 15862-15862
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6203778
- OpenAlex
- W2895787947
- Cited by
- 71
- References
- 42
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 5 · 2022: 8 · 2021: 12 · 2020: 18 · 2019: 11 · 2018: 1
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Gredos (University of Salamanca) (publishedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Hispana (submittedVersion, cc-by-nc-nd)
- Funders
- Ministerio de Economía y Competitividad (CIBERehd CB06/04/0071, FJCI-2015–25040, PI16/)
- Generalitat Valenciana (GRISOLIAP/2016/015, CB06/04/0071, CIBERehd CB06/04/0071)
- Universitat de València
- Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FI17/00144, CB06/04/0071, UGP-15-144, GV/2016/169)
- Instituto de Salud Carlos III (PI16/, CPII16/00037, PROMETEOII 2014/035, FI14/00350, CD14/00043, FI17/00144, CES10/030, CB06/04/0071, PI16/01083, PI16/00301, FI17/00126, GV/2016/169, CD14/, FI14/00125, CIBERehd CB06/04/0071)
- European Regional Development Fund (FI14/00125, PROMETEOII 2014/035, CD14/00043, CB06/04/0071, CIBERehd CB06/04/0071, FI17/00144)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- SS-31, type 2 diabetes, SIRT1, mitochondrial antioxidants, leukocyte-endothelium interaction, oxidative stress, inflammation, mitochondrial reactive oxygen species, mitochondrial membrane potential, glutathione, NF-κB, TNF-α, leukocyte rolling, cardiovascular risk
- MeSH terms
- Aged, Antioxidants, Cell Adhesion, Diabetes Mellitus, Type 2, Female, Humans, Inflammation, Leukocytes, Male, Middle Aged, Mitochondria, Oligopeptides, Up-Regulation, Case-Control Studies, Reactive Oxygen Species, Oxidative Stress, Transcription Factor RelA, Membrane Potential, Mitochondrial, Sirtuin 1, Human Umbilical Vein Endothelial Cells
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