Palmitic acid increases pro-oxidant adaptor protein p66Shc expression and affects vascularization factors in angiogenic mononuclear cells: Action of resveratrol
| Autor: | Pieter Koolwijk, Erik H. Serné, René J. P. Musters, Juan-Jesus Garcia-Vallejo, J.M. Baggen, Tineke C. T. M. van der Pouw Kraan, Anton J.G. Horrevoets, Weena J.Y. Chen, Larissa W. van Golen, Thomas A. Leyen, Michaela Diamant, Ruud D. Fontijn, Renate E. van Genugten, Julie Favre, Cansu Yıldırım |
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| Přispěvatelé: | Molecular cell biology and Immunology, Internal medicine, Physiology, ICaR - Ischemia and repair |
| Rok vydání: | 2015 |
| Předmět: |
Male
Src Homology 2 Domain-Containing Transforming Protein 1 endocrine system diseases Physiology Palmitic Acid Neovascularization Physiologic Context (language use) Oxidative phosphorylation Resveratrol Pharmacology medicine.disease_cause Antioxidants chemistry.chemical_compound NEFA Cell Movement Stilbenes medicine Humans Gene Silencing Cells Cultured Metabolic Syndrome Middle Aged Pro-oxidant Oxidative Stress chemistry Diabetes Mellitus Type 2 Gene Expression Regulation Shc Signaling Adaptor Proteins Case-Control Studies KLF2 Leukocytes Mononuclear Molecular Medicine Tumor necrosis factor alpha Oxidative stress |
| Zdroj: | Favre, J, Yildirim, C, Leyen, T A, Chen, J Y, van Genugten, R E, van Golen, L W, Garcia Vallejo, J J, Musters, R J P, Baggen, J M, Fontijn, R D, van der Pouw-Kraan, T C T M, Serne, E H, Koolwijk, P, Diamant, M & Horrevoets, A J 2015, ' Palmitic acid increases pro-oxidant adaptor protein p66Shc expression and affects vascularization factors in angiogenic mononuclear cells: Action of resveratrol ', Vascular Pharmacology, vol. 75, pp. 7-18 . https://doi.org/10.1016/j.vph.2015.08.003 Vascular Pharmacology, 75, 7-18. Elsevier Inc. |
| ISSN: | 1879-3649 1537-1891 |
| DOI: | 10.1016/j.vph.2015.08.003 |
| Popis: | A defect in neo-vascularization process involving circulating angiogenic mononuclear cells (CACs) dysfunction is associated with diabetes. We showed that oxidative stress was elevated in CACs cultured from blood of individuals with metabolic syndrome (MetS) and diabetes. We then assessed the action of palmitic acid (PA), a deregulated and increased NEFA in metabolic disorders, focusing on its oxidant potential. We observed that the phyto-polyphenol resveratrol normalized oxidative stress both in CACs isolated from MetS patients or treated with PA. Resveratrol further decreased the deleterious action of PA on gene expression of vascularization factors (TNFα, VEGF-A, SDF1α, PECAM-1, VEGFR2, Tie2 and CXCR4) and improved CAC motility. Particularly, resveratrol abolished the PA-induced over-expression of the pro-oxidant protein p66Shc. Neither KLF2 nor SIRT1, previously shown in resveratrol and p66Shc action, was directly involved. Silencing p66Shc normalized PA action on VEGF-A and TNFα specifically, without abolishing the PA-induced oxidative stress, which suggests a deleterious role of p66Shc independently of any major modulation of the cellular oxidative status in a high NEFA levels context. Besides showing that resveratrol reverses PA-induced harmful effects on human CAC function, certainly through profound cellular modifications, we establish p66Shc as a major therapeutic target in metabolic disorders, independent from glycemic control. |
| Databáze: | OpenAIRE |
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