Blockage of progesterone receptor effectively protects pancreatic islet beta cell viability

doi:10.1016/j.steroids.2013.06.005

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	Blockage of progesterone receptor effectively protects pancreatic islet beta cell viability
	Zhou, Rong 2; Yao, Xingang 1; Xu, Xing 1; Wang, Gaihong 1; Zhu, Zhiyuan 1; Chen, Jing1 ; Chen, Lili1 ; Shen, Xu1,2
刊名	STEROIDS
	2013-10
卷号	78 期号:10 页码:987-995
关键词	Progesterone receptor Diabetes SC51089 Pro-inflammatory cytokines Pancreatic islet beta cells
ISSN号	0039-128X
DOI	10.1016/j.steroids.2013.06.005
文献子类	Article
英文摘要	The progesterone receptor (PR), a member of nuclear receptor superfamily, is closely associated with gestational, type 1 and type 2 diabetes. However, the underlying mechanisms remain obscure. Here we found that PR activation increased the pro-inflammatory cytokines (PIC)-induced injury in Min6 cells, and PR blockage with siRNA interference protected the cells from damage. Moreover, the new discovered PR antagonist SC51089 effectively improved cell survival by reducing the PLC-stimulated cell apoptosis in Min6 cells. Immunoblotting assays indicated that either PR agonist progesterone (P4) or PR-B overexpression promoted the PLC-induced reinforces of extracellular-signal-regulated kinase 1/2 phosphorylation (p-Erk) and protein 53 (p53), and the attenuations of protein kinase B phosphorylation (p-ART) and tumor necrosis factor receptor-associated factor 2 (TRAF2). SC51089 could reverse all the P4- or PR-B over-expression induced effects. In addition, PR siRNA inference based assay further supported that SC51089 protected pancreatic islet beta cells from the PR activation or PLC-induced injury by targeting PR and this protective action was mediated by ART signaling pathway. To our knowledge, this current work might be the first report on the regulation of PR in pancreatic islet beta cell survival. It is expected that SC51089, as a non-steroid PR antagonist, might also find its potential in anti-diabetic research. (C) 2013 Elsevier Ltd. All rights reserved.
资助项目	State Key Program of Basic Research of China[2010CB912501] ; State Key Program of Basic Research of China[2012ZX09301001-004] ; National Natural Science Foundation of China[81173105] ; National Natural Science Foundation of China[81220108025] ; National Natural Science Foundation of China[91213306] ; Foundation of Chinese Academy of Sciences[KSCX2-EW-Q-3]
WOS关键词	GESTATIONAL DIABETES-MELLITUS ; RAT ; APOPTOSIS ; INFLAMMATION ; ANTAGONISTS ; INHIBITION ; ACTIVATION ; MODULATOR ; ISOFORMS ; TYPE-1
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000324443500004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277449]
专题	生物技术药物研发中心（筹）中科院受体结构与功能重点实验室新药研究国家重点实验室药理学第三研究室
通讯作者	Chen, Lili
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug 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	Zhou, Rong,Yao, Xingang,Xu, Xing,et al. Blockage of progesterone receptor effectively protects pancreatic islet beta cell viability[J]. STEROIDS,2013,78(10):987-995.
APA	Zhou, Rong.,Yao, Xingang.,Xu, Xing.,Wang, Gaihong.,Zhu, Zhiyuan.,...&Shen, Xu.(2013).Blockage of progesterone receptor effectively protects pancreatic islet beta cell viability.STEROIDS,78(10),987-995.
MLA	Zhou, Rong,et al."Blockage of progesterone receptor effectively protects pancreatic islet beta cell viability".STEROIDS 78.10(2013):987-995.