Department of Geriatrics, RenJi Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.
Mol Cell Biochem. 2011 Dec;358(1-2):21-9. doi: 10.1007/s11010-011-0915-1. Epub 2011 Jun 10.
Angiotensin II (Ang II) plays a profound regulatory effect on NADPH oxidase and the functional features of vascular adventitial fibroblasts, but its role in antioxidant enzyme defense remains unclear. This study investigated the effect of Ang II on expressions and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in adventitial fibroblasts and the possible mechanism involved. Ang II decreased the expression and activity of CAT in a dose- and time-dependent manner, but not that of SOD and GPx. The effects were abolished by the angiotensin II type 1 receptor (AT1R) blocker losartan and AT1R small-interfering RNA (siRNA). Incubation with polyethylene glycol-CAT prevented the Ang II-induced effects on reactive oxygen species (ROS) generation and myofibroblast differentiation. Moreover, Ang II rapidly induced phosphorylation of ERK1/2, which was reversed by losartan and AT1R siRNA. Pharmacological blockade of ERK1/2 improved Ang II-induced decrease in CAT protein expression. These in vitro results indicate that Ang II induces ERK1/2 activation, contributing to the downregulation of CAT as well as promoting oxidative stress and adventitial fibroblast phenotypic differentiation in an AT1R-mediated manner.
血管紧张素 II（Ang II）对 NADPH 氧化酶和血管外膜成纤维细胞的功能特征具有深远的调节作用，但它在抗氧化酶防御中的作用尚不清楚。本研究探讨了 Ang II 对血管外膜成纤维细胞中超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）表达和活性的影响及其可能的机制。Ang II 呈剂量和时间依赖性降低 CAT 的表达和活性，但不影响 SOD 和 GPx。这些作用被血管紧张素 II 型 1 受体（AT1R）阻滞剂洛沙坦和 AT1R 小干扰 RNA（siRNA）所消除。用聚乙二醇-CAT 孵育可防止 Ang II 诱导的活性氧（ROS）生成和肌成纤维细胞分化。此外，Ang II 可快速诱导 ERK1/2 磷酸化，洛沙坦和 AT1R siRNA 可逆转该作用。ERK1/2 的药理学阻断可改善 Ang II 诱导的 CAT 蛋白表达下降。这些体外结果表明，Ang II 诱导 ERK1/2 激活，导致 CAT 下调，并以 AT1R 介导的方式促进氧化应激和血管外膜成纤维细胞表型分化。
