Presentation Title

Regulation of Peroxisome Proliferator-Activated Receptor-gamma mRNA Expression by Angiotensin II and Arachidonyl-2-Chloroethylamide

Presenter Credentials

Research Associate/Instructor

Presenter Degree

Ph.D.

Co-Author Credentials

Michelle A. Clark, Ph.D Dean and Professor

College

College of Pharmacy

Campus Location

Ft. Lauderdale

Format

Event

IRB Approval Verification

N/A

Abstract

Purpose: Effect of arachidonyl-2-chloroethylamide (ACEA; synthetic cannabinoid receptor agonist) on Angiotensin (Ang) II-induced effects on peroxisome proliferator-activated receptor gamma (PPARg). Background: Ang II, a ligand of the renin angiotensin system (RAS) activates the NFKB/Cox2/PGE2 inflammatory signaling pathway. There is an interaction between the RAS and the endocannabinoid system. Whether the interaction between the two systems elicits synergistic or antagonist effects on each other requires further studies. Thus, we investigated the role of CB1R agonism on the effects of Ang II on PPARg mRNA expression and the NFKB/Cox2/PGE2 pathway. We previously observed that ACEA activated NFKB but had no effect on Cox2 at 12-24 hours of ACEA treatment. PGE2 levels were decreased or not affected by ACEA treatments. PPARg was selected as a target because activating this receptor leads to inhibition of NFKB. Understanding the molecular interaction between the two systems may identify potential therapeutic targets to attenuate Ang II effects. Methods: Quiescent brainstem and cerebellum astrocytes were treated with 10nM ACEA and/or 100nM Ang II for 12-24 hours. PPARg mRNA was determined by quantitative polymerase chain reaction. Results: Ang II decreased PPARg mRNA in most samples. The decrease was more pronounced in the brainstem compared to the cerebellum astrocytes. ACEA did not significantly alter PPARg mRNA. Treating astrocytes with both Ang II and ACEA did not significantly alter Ang II’s effects. Conclusions: Given these findings and our previous results, Ang II and ACEA have contrasting effects on the neuroinflammatory pathway examined. ACEA did not appear to alter the Ang II effects examined. ACEA activated the NFKB pathway and decreased PGE2 levels but had no effect on PPARg and Cox2 at the time intervals examined. Other pathway interactions might account for ACEA effects. Evaluation of protein expression for selected targets from this pathway will complement these results and these studies are planned.

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Regulation of Peroxisome Proliferator-Activated Receptor-gamma mRNA Expression by Angiotensin II and Arachidonyl-2-Chloroethylamide

Purpose: Effect of arachidonyl-2-chloroethylamide (ACEA; synthetic cannabinoid receptor agonist) on Angiotensin (Ang) II-induced effects on peroxisome proliferator-activated receptor gamma (PPARg). Background: Ang II, a ligand of the renin angiotensin system (RAS) activates the NFKB/Cox2/PGE2 inflammatory signaling pathway. There is an interaction between the RAS and the endocannabinoid system. Whether the interaction between the two systems elicits synergistic or antagonist effects on each other requires further studies. Thus, we investigated the role of CB1R agonism on the effects of Ang II on PPARg mRNA expression and the NFKB/Cox2/PGE2 pathway. We previously observed that ACEA activated NFKB but had no effect on Cox2 at 12-24 hours of ACEA treatment. PGE2 levels were decreased or not affected by ACEA treatments. PPARg was selected as a target because activating this receptor leads to inhibition of NFKB. Understanding the molecular interaction between the two systems may identify potential therapeutic targets to attenuate Ang II effects. Methods: Quiescent brainstem and cerebellum astrocytes were treated with 10nM ACEA and/or 100nM Ang II for 12-24 hours. PPARg mRNA was determined by quantitative polymerase chain reaction. Results: Ang II decreased PPARg mRNA in most samples. The decrease was more pronounced in the brainstem compared to the cerebellum astrocytes. ACEA did not significantly alter PPARg mRNA. Treating astrocytes with both Ang II and ACEA did not significantly alter Ang II’s effects. Conclusions: Given these findings and our previous results, Ang II and ACEA have contrasting effects on the neuroinflammatory pathway examined. ACEA did not appear to alter the Ang II effects examined. ACEA activated the NFKB pathway and decreased PGE2 levels but had no effect on PPARg and Cox2 at the time intervals examined. Other pathway interactions might account for ACEA effects. Evaluation of protein expression for selected targets from this pathway will complement these results and these studies are planned.