Connexin 43 stabilizes astrocytes in a stroke-like milieu to facilitate neuronal recovery

doi:10.1038/aps.2015.39

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	Connexin 43 stabilizes astrocytes in a stroke-like milieu to facilitate neuronal recovery
	Wu, Le-yu; Yu, Xue-li; Feng, Lin-yin
刊名	ACTA PHARMACOLOGICA SINICA
	2015-08
卷号	36 期号:8 页码:928-938
关键词	astrocytes Connexin 43 oxygen-glucose deprivation/recovery middle cerebral artery occlusion CREB Ephrin-A4 calcium
ISSN号	1671-4083
DOI	10.1038/aps.2015.39
文献子类	Article
英文摘要	Aim: Connexin 43 (Cx43) is a member of connexin family mainly expressed in astrocytes, which forms gap junctions and hemichannels and maintains the normal shape and function of astrocytes. In this study we investigated the role of Cx43 in astrocytes in facilitating neuronal recovery during ischemic stroke. Methods: Primary culture of astrocytes or a mixed culture of astrocytes and cortical neurons was subjected to oxygen glucose deprivation and reperfusion (OGD/R). The expression of Cx43 and Ephrin-A4 in astrocytes was detected using immunocytochemical staining and Western blot assays. Intercellular Ca2+ concentration was determined with Fluo-4 AM fluorescent staining. Middle cerebral artery occlusion (MCAO) model rats were used for in vivo studies. Results: OGD/R treatment of cultured astrocytes caused a decrement of Cx43 expression and translocation of Cx43 from cell membrane to cytoplasm, accompanied by cell retraction. Furthermore, OGD/R increased intracellular Ca2+ concentration, activated CaMKII/CREB pathways and upregulated expression of Ephrin-A4 in the astrocytes. All these changes in OGD/R-treated astrocytes were alleviated by overexpression of Cx43. In the cortical neurons cultured with astrocytes, OGD/R inhibited the neurite growth, whereas overexpression of Cx43 or knockdown of Ephrin-A4 in astrocytes restored the neurite growth. In MCAO model rats, neuronal recovery was found to be correlated with the recuperation of Cx43 and Ephrin-A4 in astrocytes. Conclusion: Cx43 can stabilize astrocytes and facilitate the resistance to the deleterious effects of a stroke-like milieu and promote neuronal recovery.
资助项目	National Natural Science Foundation of China[81123004] ; Chinese Academy of Sciences[XDA01040304] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2014ZX09102-001-05]
WOS关键词	SULFATE PROTEOGLYCANS NEUROCAN ; GAP JUNCTIONAL COMMUNICATION ; CULTURED ASTROCYTES ; CORTICAL ASTROCYTES ; NEURITE OUTGROWTH ; CEREBRAL-ISCHEMIA ; CALCIUM INFLUX ; HEMICHANNELS ; EXPRESSION ; CYTOKINES
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:5487142
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000358934000004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276452]
专题	药理学第二研究室
通讯作者	Feng, Lin-yin
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wu, Le-yu,Yu, Xue-li,Feng, Lin-yin. Connexin 43 stabilizes astrocytes in a stroke-like milieu to facilitate neuronal recovery[J]. ACTA PHARMACOLOGICA SINICA,2015,36(8):928-938.
APA	Wu, Le-yu,Yu, Xue-li,&Feng, Lin-yin.(2015).Connexin 43 stabilizes astrocytes in a stroke-like milieu to facilitate neuronal recovery.ACTA PHARMACOLOGICA SINICA,36(8),928-938.
MLA	Wu, Le-yu,et al."Connexin 43 stabilizes astrocytes in a stroke-like milieu to facilitate neuronal recovery".ACTA PHARMACOLOGICA SINICA 36.8(2015):928-938.