BACKGROUND: Angiotensin II (Ang II) induces oxidative stress and apoptosis in vascular endothelial cells. We hypothesized that propofol may attenuate Ang II-induced apoptosis in human coronary artery endothelial cells (HCAECs) and aimed to identify the underlying mechanisms. METHODS: Endothelial cells were pre-treated with propofol and then stimulated with Ang II. Apoptosis was examined by TUNEL, DNA laddering, and caspase-3 activity assays. The effect of propofol on Ang II-modulated NADPH oxidase expression and activity, nitric oxide synthase III (NOSIII) expression and phosphorylation and activity, lipid peroxidation, superoxide anion generation, nitric oxide production, caspase activity, and protein expression of cytochrome c, Bcl-2, and C-IAP-1 were measured. RESULTS: Ang II induced apoptosis, which was attenuated by 50 µM propofol (P<0.05). Propofol ameliorated Ang II-induced NADPH oxidase expression and activation (P<0.01), lipid peroxidation (P<0.05), and superoxide anion generation (P<0.05), whereas restoring NOSIII phosphorylation and activity (P<0.01) were down-regulated by Ang II. Propofol attenuated Ang II-modulated cytochrome c release, and the expression of Bcl-2 and C-IAP-1. In addition, propofol inhibited Ang II-induced caspase-9 (P<0.01) and caspase-3 activity (P<0.01). CONCLUSIONS: Propofol protected HCAECs from Ang II-induced apoptosis by interfering with the generation of oxidative stress and redox-sensitive apoptotic pathways.
BACKGROUND:Angiotensin II (Ang II) induces oxidative stress and apoptosis in vascular endothelial cells. We hypothesized that propofol may attenuate Ang II-induced apoptosis in human coronary artery endothelial cells (HCAECs) and aimed to identify the underlying mechanisms. METHODS: Endothelial cells were pre-treated with propofol and then stimulated with Ang II. Apoptosis was examined by TUNEL, DNA laddering, and caspase-3 activity assays. The effect of propofol on Ang II-modulated NADPH oxidase expression and activity, nitric oxide synthase III (NOSIII) expression and phosphorylation and activity, lipid peroxidation, superoxide anion generation, nitric oxide production, caspase activity, and protein expression of cytochrome c, Bcl-2, and C-IAP-1 were measured. RESULTS:Ang II induced apoptosis, which was attenuated by 50 µM propofol (P<0.05). Propofol ameliorated Ang II-induced NADPH oxidase expression and activation (P<0.01), lipid peroxidation (P<0.05), and superoxide anion generation (P<0.05), whereas restoring NOSIII phosphorylation and activity (P<0.01) were down-regulated by Ang II. Propofol attenuated Ang II-modulated cytochrome c release, and the expression of Bcl-2 and C-IAP-1. In addition, propofol inhibited Ang II-induced caspase-9 (P<0.01) and caspase-3 activity (P<0.01). CONCLUSIONS:Propofol protected HCAECs from Ang II-induced apoptosis by interfering with the generation of oxidative stress and redox-sensitive apoptotic pathways.
Authors: Bianca P Campagnaro; Clarissa L Tonini; Luciano M Doche; Breno V Nogueira; Elisardo C Vasquez; Silvana S Meyrelles Journal: DNA Cell Biol Date: 2013-06-20 Impact factor: 3.311
Authors: Bianca P Campagnaro; Clarissa L Tonini; Breno V Nogueira; Dulce E Casarini; Elisardo C Vasquez; Silvana S Meyrelles Journal: Int J Hypertens Date: 2013-02-14 Impact factor: 2.420