title: Resveratrol inhibits angiotensin II-induced ERK1/2 activation by downregulating quinone reductase 2 in rat vascular smooth muscle cells.
abstract: Our previous studies showed that resveratrol could inhibit the proliferation of vascular smooth muscle cells (VSMCs) and repress mRNA and protein expression of quinone reductase 2 (NQO2). This study further explored the potential mechanisms whereby resveratrol inhibits the proliferation of rat VSMCs. Lentiviral vectors that incorporated NQO2 small interfering RNA (siRNA) were constructed and transduced into rat VSMCs. The cell proliferation was detected using the bromodeoxyuridine (BrdU) assay. Cultured rat VSMCs were stimulated with angiotensin II and the level of reactive oxygen species (ROS) was measured using a ROS assay kit. A realtime quantitative PCR was used to detect NQO2 mRNA levels. Extracellular signal-regulated kinase (ERK1/2) and NQO2 protein expression were determined by Western blotting analysis. The inhibitory effect of resveratrol (10 and 50 µmol/L) on the proliferation of rat VSMCs in the NQO2 siRNA group was significantly weaker than that in the normal and scrambled siRNA group (P < 0.01). The ROS level in the NQO2 siRNA and resveratrol (50 µmol/L) treatment groups were lower than that in the normal and scrambled siRNA groups (P < 0.01 in both). Compared with the normal and scrambled siRNA group, the phosphorylation of ERK1/2 was significantly decreased in the NQO2 siRNA and resveratrol (50 µmol/L) treatment group (P < 0.01 in both). In conclusion, high concentration of resveratrol inhibits angiotensin II-induced ERK1/2 phosphorylation and subsequent proliferation by down-regulation of NQO2 in cultured rat VSMCs.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China;
authors.forename: Xiwen
authors.initials: X
authors.lastname: Zhang
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Hou
authors.forename: Jiangang
authors.initials: J
authors.lastname: Zou
authors.forename: Kejiang
authors.initials: K
authors.lastname: Cao
keywords: extracellular signal-regulated kinase (ERK); quinone reductase 2 (NQO2); reactive oxygen species; resveratrol; vascular smooth muscle cells
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