Effect of PGE2-EPs pathway on primary cultured rat neuron injury caused by aluminum

Lu Yang; Yuling Wei; Ying Luo; Qunfang Yang; Huan Li; Congli Hu; Yang Yang; Junqing Yang

doi:10.18632/oncotarget.21122

Effect of PGE₂-EP_s pathway on primary cultured rat neuron injury caused by aluminum

Oncotarget. 2017 Sep 21;8(54):92004-92017. doi: 10.18632/oncotarget.21122. eCollection 2017 Nov 3.

Authors

Lu Yang¹, Yuling Wei¹, Ying Luo¹, Qunfang Yang¹, Huan Li¹, Congli Hu¹, Yang Yang¹, Junqing Yang¹

Affiliation

¹ Department of Pharmacology, Chongqing Medical University, The Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.

Abstract

To observe the characteristic changes of PGE₂-EP_s pathway and divergent functions of PGE₂ receptor subtypes on neuronal injury. The primary cultured rat hippocampus neuron injury model was established via aluminum maltolate (100 μM). The aluminum-overload neurons were treated with the agonists of EP1 (17-phenyl trinor Prostaglandin E2 ethyl amide), EP2 (Butaprost), EP3 (Sulprostone) and EP4 (CAY10598) and antagonists of EP1 (SC-19220), EP2 (AH6809) and EP4 (L-161982) at different concentrations, respectively. The neuronal viability, lactate dehydrogenase leakage rate and PGE2 content were detected by MTT assay, lactate dehydrogenase assay kit and enzyme-linked immunosorbent assay, respectively. The mRNA and protein expressions of mPGES-1 and EPs were determined by RT-PCR and western blot, respectively. The pathomorphology was identified by hematoxylin-eosin staining. In the model group, neuronal viability significantly decreased, while lactate dehydrogenase leakage rate and PGE2 content increased. The mPGES-1, EP1, EP2 and EP4 mRNA expression, and the mPGES-1, EP1 and EP2 protein expression increased, while EP₃ level decreased. EP3 agonist exerted protective function in neuronal viability and lactate dehydrogenase leakage rate, while EP1 agonist, EP2 and EP4 antagonist exerted an opposite effect. In conclusion, aluminum-overload caused an imbalance of PGE₂-EP_1-4 pathway and activation of EP receptor may provide a viable therapeutic target in neuronal injury.

Keywords: PGE2; PGE2 receptor; aluminum overload; hippocampal neuron.