Sinomenine activates astrocytic dopamine D2 receptors and alleviates neuroinflammatory injury via the CRYAB

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	Sinomenine activates astrocytic dopamine D2 receptors and alleviates neuroinflammatory injury via the CRYAB
其他题名	Sinomenine activates astrocytic dopamine D2 receptors and alleviates neuroinflammatory injury via the CRYAB
	Jing Qiu 1; Zhongjun Yan 2; Kai Tao 2; Yansong Li 3; Yuqian Li 2; Jingchen Li 1; Yushu Dong 1; Dayun Feng 2; Huisheng Chen 1
	2016-01-01
发表期刊	Journal of Neuroinflammation
ISSN	1742-2094
卷号	13 期号:1
摘要	Astrocyte-mediated neuroinflammation plays a critical role in ischemic stroke-induced secondary cerebral injury. Previous studies have suggested that the dopamine D2 receptor (DRD2) acts as a key target in regulating the neuroinflammatory response. However, the underlying molecular mechanisms are still unknown, and effective DRD2 agonists are lacking. In the present study, we examined the anti-inflammatory and neuroprotective effects of sinomenine (Sino), a monomeric compound with potential immunoregulatory properties in nervous system.
其他摘要	Background Astrocyte-mediated neuroinflammation plays a critical role in ischemic stroke-induced secondary cerebral injury. Previous studies have suggested that the dopamine D2 receptor (DRD2) acts as a key target in regulating the neuroinflammatory response. However, the underlying molecular mechanisms are still unknown, and effective DRD2 agonists are lacking. In the present study, we examined the anti-inflammatory and neuroprotective effects of sinomenine (Sino), a monomeric compound with potential immunoregulatory properties in nervous system. Methods TTC staining, apoptosis assay, evaluation of brain edema, and neurological assessment were performed in the middle cerebral artery occlusion (MCAO) mouse model. Primary astrocytes exposed to oxygen glucose deprivation (OGD) were used in the in vitro experiments. Quantitative PCR was applied to assess the levels of inflammatory cytokines. Multi-labeling immunofluorescence, Western blot, co-immunoprecipitation, and electrophoretic mobility shift assay (EMSA) were also used to investigate the molecular mechanisms underlying the Sino-mediated anti-inflammatory effects in vivo and in vitro. Results Sino remarkably attenuated the cerebral infarction and neuronal apoptosis, reduced the levels of inflammatory cytokines, and alleviated neurological deficiency in MCAO mice. Sino significantly inhibited astrocytic activation and STAT3 phosphorylation as well as increased DRD2 and αB-crystallin (CRYAB) expression after MCAO. In vitro, Sino blocked OGD-induced activation of STAT3 and generation of pro-inflammatory cytokines in primary astrocytes, and these effects were significantly abolished by either DRD2 or CRYAB knockdown. Additionally, Sino induced up-regulation and nuclear translocation of CRYAB in astrocytes and enhanced the interaction between CRYAB and STAT3, which further inhibited the activation and DNA-binding activity of STAT3. Conclusions Our study demonstrates that Sino activates astrocytic DRD2 and thereby suppresses neuroinflammation via the CRYAB Electronic supplementary material The online version of this article (doi:10.1186
语种	英语
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/159461
专题	中国科学院金属研究所
作者单位	1.Institute of Metal Research, Chinese Academy of Sciences 2.中国人民解放军第四军医大学 3.The 463rd Hospital of PLA
推荐引用方式 GB/T 7714	Jing Qiu,Zhongjun Yan,Kai Tao,et al. Sinomenine activates astrocytic dopamine D2 receptors and alleviates neuroinflammatory injury via the CRYAB[J]. Journal of Neuroinflammation,2016,13(1).
APA	Jing Qiu.,Zhongjun Yan.,Kai Tao.,Yansong Li.,Yuqian Li.,...&Huisheng Chen.(2016).Sinomenine activates astrocytic dopamine D2 receptors and alleviates neuroinflammatory injury via the CRYAB.Journal of Neuroinflammation,13(1).
MLA	Jing Qiu,et al."Sinomenine activates astrocytic dopamine D2 receptors and alleviates neuroinflammatory injury via the CRYAB".Journal of Neuroinflammation 13.1(2016).