A Critical Role for Interferon Regulatory Factor 9 in Cerebral Ischemic Stroke

CORC > 武汉物理与数学研究所 > 中国科学院武汉物理与数学研究所 > 磁共振基础研究部

	A Critical Role for Interferon Regulatory Factor 9 in Cerebral Ischemic Stroke
	Chen, Hou-Zao 1,2; Guo, Sen 3,4; Li, Zuo-Zhi 1,2; Lu, Yanyun 3,4; Jiang, Ding-Sheng 3,4; Zhang, Ran 1,2; Lei, Hao 5; Gao, Lu 6; Zhang, Xiaofei 7; Zhang, Yan 3,4
刊名	JOURNAL OF NEUROSCIENCE
	2014-09-03
卷号	34 期号:36 页码:11897-11912
关键词	IRF9 stroke Sirt1 p53 neuroapoptosis
英文摘要	The failure of past efforts to develop effective stroke treatments is at least partially because these treatments often interfered with essential physiological functions, even though they are targeted toward pathophysiological events, such as inflammation, excitotoxicity, and oxidative stress. Thus, the direct targeting of endogenous neuroprotective or destructive elements holds promise as a potential new approach to treating this devastating condition. Interferon regulatory factor 9 (IRF9), a transcription factor that regulates innate immune responses, has been implicated in neurological pathology. Here, we provide new evidence that IRF9 directly mediates neuronal death in male mice. In response to ischemia/reperfusion (I/R), IRF9 accumulated in neurons. IRF9 deficiency markedly mitigated both poststroke neuronal death and neurological deficits, whereas the neuron-specific overexpression of IRF9 sensitized neurons to death. The histone deacetylase Sirt1 was identified as a novel negative transcriptional target of IRF9 both in vivo and in vitro. IRF9 inhibits Sirt1 deacetylase activity, culminating in the acetylation and activation of p53-mediated cell death signaling. Importantly, both the genetic and pharmacological manipulation of Sirt1 effectively counteracted the pathophysiological effects of IRF9 on stroke outcome. These findings indicate that, rather than activating a delayed innate immune response, IRF9 directly activates neuronal death signaling pathways through the downregulation of Sirt1 deacetylase in response to acute I/R stress.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Neurosciences
研究领域[WOS]	Neurosciences & Neurology
关键词[WOS]	CENTRAL-NERVOUS-SYSTEM ; BRAIN-INJURY ; IRF FAMILY ; TRANSCRIPTION FACTORS ; NEURONAL DEATH ; SIRT1 ; PROTECTS ; P53 ; MECHANISMS ; EXPRESSION
收录类别	SCI
语种	英语
WOS记录号	WOS:000341765400005
公开日期	2015-07-14
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/1469]
专题	武汉物理与数学研究所_磁共振基础研究部
作者单位	1.Chinese Acad Med Sci, Inst Basic Med Sci, Dept Biochem & Mol Biol, State Key Lab Med Mol Biol, Beijing 100005, Peoples R China 2.Peking Union Med Coll, Beijing 100005, Peoples R China 3.Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China 4.Wuhan Univ, Cardiovasc Res Inst, Wuhan 430060, Peoples R China 5.Chinese Acad Sci, Wuhan Inst Phys & Math, Wuhan Ctr Magnet Resonance, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Peoples R China 6.Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Cardiol,Inst Cardiovasc Dis, Wuhan 430022, Peoples R China 7.Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China 8.Wuhan Univ, Sch Med, Dept Immunol, State Key Lab Virol, Wuhan 430071, Peoples R China 9.Wuhan Univ, Sch Med, Hubei Prov Key Lab Allergy & Immunol, Wuhan 430071, Peoples R China 10.Fourth Mil Med Univ, Xijing Hosp, Dept Anesthesiol, Xian 710032, Peoples R China
推荐引用方式 GB/T 7714	Chen, Hou-Zao,Guo, Sen,Li, Zuo-Zhi,et al. A Critical Role for Interferon Regulatory Factor 9 in Cerebral Ischemic Stroke[J]. JOURNAL OF NEUROSCIENCE,2014,34(36):11897-11912.
APA	Chen, Hou-Zao.,Guo, Sen.,Li, Zuo-Zhi.,Lu, Yanyun.,Jiang, Ding-Sheng.,...&Li, Hongliang.(2014).A Critical Role for Interferon Regulatory Factor 9 in Cerebral Ischemic Stroke.JOURNAL OF NEUROSCIENCE,34(36),11897-11912.
MLA	Chen, Hou-Zao,et al."A Critical Role for Interferon Regulatory Factor 9 in Cerebral Ischemic Stroke".JOURNAL OF NEUROSCIENCE 34.36(2014):11897-11912.