Regulation of prostaglandin F-2 alpha, against beta amyloid clearance and its inflammation induction through LXR/RXR heterodimer antagonism in microglia

doi:10.1016/j.prostaglandins.2013.09.002

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	Regulation of prostaglandin F-2 alpha, against beta amyloid clearance and its inflammation induction through LXR/RXR heterodimer antagonism in microglia
	Zhuang, Jingjing 2; Zhang, Haikun 2; Zhou, Rong 2; Chen, Lili1 ; Chen, Jing1 ; Shen, Xu1,2
刊名	PROSTAGLANDINS & OTHER LIPID MEDIATORS
	2013-10
卷号	106 页码:45-52
关键词	Prostaglandin F-2 alpha Alzheimer's disease A beta clearance Inflammation Microglia
ISSN号	1098-8823
DOI	10.1016/j.prostaglandins.2013.09.002
文献子类	Article
英文摘要	Alzheimer's disease (AD) is characterized by extracellular deposit of beta-amyloid (A beta) and accumulation of intracellular neurofibrillary tangles in the brain. Prostaglandin F-2 alpha, (PGF(2 alpha)) is one of the major metabolites of arachidonic acid (AA), and plays essential roles in a series of key physiological processes like luteolysis and parturition. Additionally, PGF(2 alpha) is also involved in the regulation of chronic and acute inflammation processes. Recent clinical studies have revealed the high content of PGE(2 alpha) metabolite, 15-keto-dihydro-PGF(2 alpha) in AD patients, implying the activation of in vivo PGF(2 alpha) biosynthesis. However, the mechanism underlying the involvement of PGF(2 alpha) in the progression of AD still remains unclear. Here we discovered that PGF(2 alpha) selectively antagonized LXR (liver X receptors)/RXR (retinoid X receptor alpha) and RXR/RXR dimers. Cell based assays indicated that PGF(2 alpha) effectively antagonized the activation of LXR agonist (t0901317) on A beta clearance via inhibiting apolipoprotein E (apoE) expression, and cell apoptosis alleviation by accelerating inflammatory response to A beta or Lipopolysaccharide (LPS) in microglia. Therefore, our current findings have addressed the potential association of PGF(2 alpha) with AD progression, and highlighted that inhibition of PGF(2 alpha) biosynthesis might be a useful therapeutic strategy against AD. (C) 2013 Elsevier Inc. All rights reserved.
资助项目	National Science & Technology Major Project "Key New Drug Creation. and Manufacturing Program"[2012ZX09103101-018] ; National Science & Technology Major Project "Key New Drug Creation. and Manufacturing Program"[2012ZX09301001-004] ; State Key Program of Basic Research of China[2010CB912501] ; Science Foundation of Shanghai[12431900300]
WOS关键词	LIVER-X-RECEPTORS ; CYTOKINE-MEDIATED INFLAMMATION ; ALZHEIMERS-DISEASE ; MOLECULAR-MECHANISMS ; ELDERLY POPULATION ; SIGNALING PATHWAY ; OXIDATIVE STRESS ; A-BETA ; BRAIN ; LXR
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000328720000007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277429]
专题	药物安全性评价中心药理学第三研究室
通讯作者	Chen, Jing
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;
推荐引用方式 GB/T 7714	Zhuang, Jingjing,Zhang, Haikun,Zhou, Rong,et al. Regulation of prostaglandin F-2 alpha, against beta amyloid clearance and its inflammation induction through LXR/RXR heterodimer antagonism in microglia[J]. PROSTAGLANDINS & OTHER LIPID MEDIATORS,2013,106:45-52.
APA	Zhuang, Jingjing,Zhang, Haikun,Zhou, Rong,Chen, Lili,Chen, Jing,&Shen, Xu.(2013).Regulation of prostaglandin F-2 alpha, against beta amyloid clearance and its inflammation induction through LXR/RXR heterodimer antagonism in microglia.PROSTAGLANDINS & OTHER LIPID MEDIATORS,106,45-52.
MLA	Zhuang, Jingjing,et al."Regulation of prostaglandin F-2 alpha, against beta amyloid clearance and its inflammation induction through LXR/RXR heterodimer antagonism in microglia".PROSTAGLANDINS & OTHER LIPID MEDIATORS 106(2013):45-52.