Prostaglandin E2 receptor 1 activity regulates cell survival following hypoxia in cultured rat cortical neurons

► EP1 affected survival of Hyp-treated neurons. ► Hyp-treatment induced neuronal apoptosis possibly through activation of EP1. ► EP1-mediated neuron apoptosis does not appear to involve cyclinD1. ► EP1 might prove to be a therapeutic target for treating ischemic brain damage. The clinical side-effec...

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Bibliographic Details
Published in:Neuroscience letters 2012-02, Vol.508 (1), p.31-36
Main Authors: Liu, Mei-ling, Zhang, Yan-qiao, Zhang, Yi-na, Pei, Li-chun, Liu, Xin
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Annexin A5 - metabolism
Caspase 3 - metabolism
Cell Survival - drug effects
Cell Survival - physiology
Cells, Cultured
Cerebral Cortex - cytology
Cyclin D1 - metabolism
CyclinD1
Dinoprostone - analogs & derivatives
Dinoprostone - pharmacology
Dose-Response Relationship, Drug
Embryo, Mammalian
Hydrazines - pharmacology
Hypoxia - metabolism
Hypoxia - pathology
Hypoxia–ischemia
Neurons
Neurons - drug effects
Neurons - metabolism
Oxazepines - pharmacology
Oxygen - administration & dosage
Prostaglandin E
Rats
Rats, Wistar
Receptors, Prostaglandin E, EP1 Subtype - agonists
Receptors, Prostaglandin E, EP1 Subtype - antagonists & inhibitors
Receptors, Prostaglandin E, EP1 Subtype - metabolism
Reoxygenation involved
Tetrazolium Salts
Thiazoles
Time Factors
Up-Regulation - drug effects
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Summary:► EP1 affected survival of Hyp-treated neurons. ► Hyp-treatment induced neuronal apoptosis possibly through activation of EP1. ► EP1-mediated neuron apoptosis does not appear to involve cyclinD1. ► EP1 might prove to be a therapeutic target for treating ischemic brain damage. The clinical side-effects of increased cyclooxygenase (COX) activity induced by pathologic conditions have raised concerns recently. However, a better understanding of the mechanisms underlying the subsequent neurotoxicity requires knowledge of pathways downstream of COX, especially prostaglandin E2 (PGE2) and its receptors. Therefore, this study was performed to investigate the effects of PGE2 receptor 1 (EP1) activity on neuronal cell death resulting from hypoxia/reoxygenation (Hyp). As cyclinD1 activity has been shown to regulate neuronal apoptosis as well, the role of cyclinD1 was investigated, as well. Cortical neural cells isolated from fetal Wistar rats were cultured for 12 d and exposed to Hyp conditions to establish an in vitro Hyp model. To determine the effects of EP1 activity on Hyp-induced neurotoxicity, cells were treated with 17-phenyl trinor-PGE2 (17-pt), a synthetic EP1 agonist, or sc-51089, an EP1 antagonist, then exposed to hypoxic conditions for 3 h and reoxygenated for 21 h. Following Hyp, cell viability was quantified by MTT assays, and apoptosis was assessed by flow cytometry. Protein expression levels of caspase-3 and cyclinD1 were examined by Western blot analysis. Treatment of cultured cortical neurons with 17-pt significantly decreased the survival rate of Hyp-treated neurons ( p < 0.05), while treatment with sc-51089 increased the survival rate. Treatment with 17-pt also led to increased expression levels of caspase-3, further supporting a role for EP1 in the observed neurotoxicity. However, cyclinD1 expression levels were unchanged following treatment with either 17-pt or sc-51089. Therefore, EP1 may play an important role in Hyp-induced neuronal apoptosis, but this neurotoxic activity is unlikely to involve cyclinD1.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2011.12.010