Autor: |
Botden IP; Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands., Oeseburg H, Durik M, Leijten FP, Van Vark-Van Der Zee LC, Musterd-Bhaggoe UM, Garrelds IM, Seynhaeve AL, Langendonk JG, Sijbrands EJ, Danser AH, Roks AJ |
Jazyk: |
angličtina |
Zdroj: |
Clinical science (London, England : 1979) [Clin Sci (Lond)] 2012 Oct; Vol. 123 (8), pp. 499-507. |
DOI: |
10.1042/CS20110679 |
Abstrakt: |
Red wine polyphenols may preserve endothelial function during aging. Endothelial cell senescence enhances age-related endothelial dysfunction. We investigated whether RWE (red wine extract) prevents oxidative-stress-induced senescence in HUVECs (human umbilical-vein endothelial cells). Senescence was induced by exposing HUVECs to tBHP (t-butylhydroperoxide), and quantified by senescence-associated β-galactosidase staining. RWE (0-50 μg/ml) concentration dependently decreased senescence by maximally 33±7.1%. RWE prevented the senescence-associated increase in p21 protein expression, inhibited tBHP-induced DNA damage of endothelial cells and induced relaxation of PCAs (porcine coronary arteries). Inhibition of SIRT1 (sirtuin 1) by sirtinol partially reversed the effect of RWE on tBHP-induced senescence, whereas both the NOS (nitric oxide synthase) inhibitor L-NMMA (NG-monomethyl-L-arginine) and the COX (cyclo-oxygenase) inhibitor indomethacin fully inhibited it. Furthermore, incubation of HUVECs with RWE increased eNOS (endothelial NOS) and COX-2 mRNA levels as well as phosphorylation of eNOS at Ser1177. RWE protects endothelial cells from tBHP-induced senescence. NO and COX-2, in addition to activation of SIRT1, play a critical role in the inhibition of senescence induction in human endothelial cells by RWE. |
Databáze: |
MEDLINE |
Externí odkaz: |
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