Palmitic acid increases pro-oxidant adaptor protein p66Shc expression and affects vascularization factors in angiogenic mononuclear cells: Action of resveratrol.
Vascul Pharmacol
; 75: 7-18, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26254104
ABSTRACT
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.
Palavras-chave
Chloromethyl-dichlorofluorescein-diacetate (PubChem CID: 90722914); Diabetes mellitus; Dimethyl sulfoxide (PubChem CID: 679); EDTA (PubChem CID: 6049); Endothelial progenitor cells; Fatty acid; Glucose (PubChem CID: 5282499); Mannitol (PubChem CID: 6251); N-Acetyl-l-cysteine (PubChem CID: 12035); Oxidative stress; Palmitic acid (PubChem CID: 985); Resveratrol (PubChem CID: 445154); SRT1720 (PubChem CID: 25232708); Sodium Dodecyl Sulfate (PubChem CID: 3423265)
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estilbenos
/
Estresse Oxidativo
/
Ácido Palmítico
/
Proteínas Adaptadoras da Sinalização Shc
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Vascul Pharmacol
Assunto da revista:
ANGIOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Holanda