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Angiotensin II induces cyclooxygenase 2 expression in rat astrocytes via the angiotensin type 1 receptor
Neuropeptides ( IF 2.5 ) Pub Date : 2019-10-01 , DOI: 10.1016/j.npep.2019.101958
Ann Tenneil O'Connor 1 , Michelle A Clark 1
Affiliation  

We previously showed that Angiotensin (Ang) II stimulated pro-inflammatory and mitogenic actions in astrocytes suggesting that astrocytes are emerging as key players in neuroinflammation. Evidence suggests that neuroinflammation may contribute to central sympathetic overactivity and elevated blood pressure. Further, cyclooxygenase (Cox)-derived prostanoids were implicated in Ang II-dependent hypertension. Cox2 is one of two Cox isoenzymes that is responsible for the formation of prostanoids from arachidonic acid. Constitutively expressed Cox2 has a protective and homeostatic role in the cardiovascular and renal systems. Inducible Cox2 has been associated with pathogenic stimuli resulting in inflammatory conditions and cancers. In this study, we investigated the effect of Ang II on Cox2 protein and mRNA expression in brainstem and cerebellum astrocytes, and determined whether any differences in Cox2 expression exist in spontaneously hypertensive rat (SHR) astrocytes compared to their normotensive control Wistar rats. We demonstrated that Ang II increased Cox2 protein and mRNA levels relative to untreated controls in a time-dependent manner, in Wistar and SHR brainstem and cerebellum astrocytes. Increases in Cox2 protein expression were evident within 4 h, with subsequent sustained elevation for several hours followed by a decline at 48 h. Ang II-induced Cox2 protein levels were higher in Wistar compared to SHRs in both brainstem and cerebellum astrocytes for the majority of time points examined. The Ang II-induced Cox2 mRNA levels increased within 8 h followed by a rapid decline to almost basal levels at later time points. At the earlier time points, Cox2 mRNA elevation were higher in SHR compared to Wistar rat astrocytes. These Ang II actions were mediated by the Ang type I receptor. Our results corroborate previous reports of Ang II's ability to stimulate neuroinflammatory mediators in astrocytes. Cox2-derived prostaglandins might play a role in brain-renin angiotensin system associated hypertension, and astrocytes could be significant players.

中文翻译:

血管紧张素 II 通过血管紧张素 1 型受体诱导大鼠星形胶质细胞中环氧合酶 2 的表达

我们以前表明血管紧张素 (Ang) II 刺激星形胶质细胞的促炎和有丝分裂作用,表明星形胶质细胞正在成为神经炎症的关键参与者。有证据表明,神经炎症可能导致中枢交感神经过度活跃和血压升高。此外,环加氧酶 (Cox) 衍生的前列腺素与 Ang II 依赖性高血压有关。Cox2 是负责从花生四烯酸形成前列腺素的两种 Cox 同工酶之一。组成型表达的 Cox2 在心血管和肾脏系统中具有保护和稳态作用。诱导型 Cox2 与导致炎症和癌症的致病刺激有关。在这项研究中,我们研究了 Ang II 对脑干和小脑星形胶质细胞中 Cox2 蛋白和 mRNA 表达的影响,并确定了自发性高血压大鼠 (SHR) 星形胶质细胞与血压正常的对照 Wistar 大鼠相比,Cox2 表达是否存在任何差异。我们证明,在 Wistar 和 SHR 脑干和小脑星形胶质细胞中,Ang II 以时间依赖性方式相对于未处理的对照增加了 Cox2 蛋白和 mRNA 水平。Cox2 蛋白表达在 4 小时内明显增加,随后持续升高数小时,然后在 48 小时时下降。在检查的大部分时间点,与脑干和小脑星形胶质细胞中的 SHR 相比,Wistar 中 Ang II 诱导的 Cox2 蛋白水平更高。Ang II 诱导的 Cox2 mRNA 水平在 8 小时内增加,随后在稍后的时间点迅速下降至几乎基础水平。在较早的时间点,与 Wistar 大鼠星形胶质细胞相比,SHR 中的 Cox2 mRNA 升高更高。这些 Ang II 作用是由 Ang I 型受体介导的。我们的结果证实了之前关于 Ang II 能够刺激星形胶质细胞中神经炎症介质的报道。Cox2 衍生的前列腺素可能在脑肾素血管紧张素系统相关的高血压中发挥作用,星形胶质细胞可能是重要的参与者。s 刺激星形胶质细胞中神经炎症介质的能力。Cox2 衍生的前列腺素可能在脑肾素血管紧张素系统相关的高血压中发挥作用,星形胶质细胞可能是重要的参与者。s 刺激星形胶质细胞中神经炎症介质的能力。Cox2 衍生的前列腺素可能在与脑肾素血管紧张素系统相关的高血压中发挥作用,星形胶质细胞可能是重要的参与者。
更新日期:2019-10-01
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