Angiotensin II Induces Cox 2 Expression in Rat Astrocytes via the Angiotensin Type 1 Receptor
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The FASEB Journal
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Federation of American Societies for Experimental Biology (FASEB)
To determine the effect of Angiotensin II on cyclooxygenase 2 expression in rat astrocytes.
We previously showed that Angiotensin (Ang) II mediated pro-inflammatory and mitogenic actions in astrocytes, and there is growing evidence that neuroinflammation may contribute to sympathoexcitation and hypertension. Further, Cox 1 derived prostanoids were implicated in Ang II-dependent hypertension. Our goal is to investigate the role of cyclooxygenase 2 (Cox 2) and its metabolites in Ang II-mediated neuroinflammatory actions in astrocytes. Cox 2 is an enzyme responsible for the synthesis of prostanoids. Prostanoids have both physiological and pathological roles, and contribute to oxidative stress. Thus, Cox 2 may have pro- or anti-inflammatory actions depending on the prostanoids that are produced. Here, we investigated the effect of Ang II on Cox 2 expression in astrocytes isolated from rat brainstem and cerebellum and determined whether any differences in Cox 2 protein levels exist in Wistar (Wis) compared to (SHRs).
Brainstem and cerebellum astrocytes were prepared from 2–3 days Wis and SHR rat pups. These brain areas express RAS components. Quiescent cells were treated with 100nM Ang II for 1 to 48hrs and Ang II receptor inhibitors for 4hrs. We determined Cox 2 protein levels by western blotting.
Ang II increased Cox 2 protein levels relative to untreated controls in a time-dependent manner, in brainstem and cerebellum for both Wis and SHRs. Increases in Cox 2 expression were evident within one hour, with a gradual decrease to almost basal levels by 48hrs. There were significant differences in Ang II-induced Cox 2 protein levels between Wis and SHRs in brainstem astrocytes. There were no significant differences in Ang II-induced Cox 2 protein levels between Wis and SHRs in cerebellum astrocytes. Ang II-induced Cox 2 protein expression in Wis brainstem astrocytes was significantly different from all other samples. These Ang II actions were mediated by the Angiotensin type I receptor (AT1R).
We demonstrated that Ang II induced Cox 2 protein expression in astrocytes. Greater elevation of Cox 2 in Wis brainstem could be attributed to the higher expression of AT1R in brainstem compared to the cerebellum. The brainstem regulates autonomic cardiovascular functions. The upstream signaling pathways and the consequences of Cox 2 elevation in rat astrocytes will be the focus of further studies.
Support or Funding Information
President’s Faculty Research and Development Grant, Nova Southeastern University
This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences
angiotensin (Ang) III, astrocytes, cyclooxygenase 2, inflammation
O'Connor, Ann Tenneil and Clark, Michelle A., "Angiotensin II Induces Cox 2 Expression in Rat Astrocytes via the Angiotensin Type 1 Receptor" (2019). Faculty Articles. 309.