title: Resveratrol ameliorates low shear stress‑induced oxidative stress by suppressing ERK/eNOS‑Thr495 in endothelial cells.
abstract: Fluid shear stress has been revealed to differentially regulate endothelial nitric oxide synthase (eNOS) distribution in vessels. eNOS, a key enzyme in controlling nitric oxide (NO) release, has a crucial role in mediating oxidative stress, and resveratrol (RSV)‑mediated eNOS also attenuates oxidative damage and suppresses endothelial dysfunction. To observe the protective effect of RSV on low shear stress (LSS)‑induced oxidative damage and the potential mechanisms involved, a parallel‑plate flow chamber, which imposed a low level of stress of 2 dynes/cm2 to cells, was employed. Reactive oxygen species (ROS), NO and apoptotic cells were examined in LSS‑treated endothelial cells (ECs) with or without RSV. Western blot analysis was used to examine LSS‑regulated eNOS‑Ser1177, Thr495 and Ser633, which were tightly associated with NO release. To further determine the underlying signaling pathways involved, extracellular signal‑regulated kinase (ERK), a possible upstream target of eNOS‑Thr495, was investigated, followed by examination of eNOS‑Thr495 in ERK‑inhibited cells. Additionally, eNOS mRNA expression levels were analyzed in cells challenged with LSS. The results revealed that RSV markedly decreased LSS‑induced oxidative damage in ECs. Furthermore, eNOS‑Ser1177 and Thr495 as well as phospho‑ERK were time‑dependently activated by LSS. The ERK inhibitor deactivated eNOS‑Thr495, which was accompanied by increased intracellular superoxide dismutase (SOD) levels. Of note, the activation effect of LSS on ERK/eNOS was markedly eliminated by RSV. In conclusion, RSV exerts antioxidant effects by suppressing LSS-activated ERK/eNOS and may provide a potential therapeutic target for atherosclerosis.
authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Wenxing
authors.initials: W
authors.lastname: Mao
authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Shao-Liang
authors.initials: SL
authors.lastname: Chen
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D033081:Shear Strength; D013267:Stilbenes / Q000494:pharmacology*; D013912:Threonine / Q000737:chemistry / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013267:Stilbenes; D013912:Threonine; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D052250:Nitric Oxide Synthase Type III; D048049:Extracellular Signal-Regulated MAP Kinases; D000077185:Resveratrol; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one