Activation of EP2 prostanoid receptors in human glial cell lines stimulates the secretion of BDNF

被引:42
作者
Hutchinson, Anthony J. [1 ]
Chou, Chih-Ling [2 ]
Israel, Davelene D. [2 ]
Xu, Wei [2 ]
Regan, John W. [1 ,2 ]
机构
[1] Univ Arizona, Coll Pharm, Program Neurosci, Tucson, AZ 85721 USA
[2] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA
基金
美国国家卫生研究院;
关键词
Prostaglandin E-2; Microglia; Astrocytes; BDNF; G-protein coupled receptor; Brain-derived neurotrophic factor; Cyclic AMP; ELEMENT-BINDING PROTEIN; NERVE GROWTH-FACTOR; NEUROTROPHIC FACTOR; PROSTAGLANDIN RECEPTOR; EXPRESSION; CLONING; NEURONS; PHOSPHORYLATION; NEUROPROTECTION; TRANSCRIPTION;
D O I
10.1016/j.neuint.2009.01.018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Prostaglandin E-2 (PGE(2)) is produced at high levels in the injured central nervous system, where it is generally considered a cytotoxic mediator of inflammation. The cellular actions of PGE(2) are mediated by G-protein signaling activated by prostanoid receptors termed EP1, EP2, EP3 and EP4. Recent studies have implicated the EP2 prostanoid receptor to be in apparently conflicting roles promoting neuronal death in some model systems and the Survival of neurons in others. Here we show that treatment of immortalized human microglia and CCF-STTG1 astrocytes with either PGE(2) or the EP2 selective agonist butaprost stimulates the release of brain-derived neurotrophic factor (BDNF). Both cell lines express mRNA for the EP2 receptor, whereas transcripts for the other subtypes are not detected. Pharmacological studies using PGE(2) and modulators of cyclic AMP signaling implicate this pathway in PGE(2)-Stimulated BDNF release. These results indicate that EP2 prostanoid receptor activation induces BDNF secretion through stimulation of cyclic AMP dependent signaling. Our findings provide a mechanism by which endogenous PGE(2) might contribute to either neurotoxicity or neuroprotection in the injured brain via the induction of BDNF release from microglial cells and astrocytes. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:439 / 446
页数:8
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