AChE deficiency or inhibition decreases apoptosis and p53 expression and protects renal function after ischemia/reperfusion

	AChE deficiency or inhibition decreases apoptosis and p53 expression and protects renal function after ischemia/reperfusion
	Ye, WY; Gong, XW; Xie, J; Wu, J; Zhang, XJ; Ouyang, Q; Zhao, XL; Shi, YF; Zhang, XJ
刊名	APOPTOSIS
	2010
卷号	15 期号:4 页码:474-487
关键词	Apoptosis Acetylcholinesterase Acetylcholinesterase inhibitors Ischemia/reperfusion
通讯作者	Zhang, XJ (reprint author), Chinese Acad Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci,Grad Sch, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,wyye@sibs.ac.cn ; xwgon@sibs.ac.cn ; jxie@sibs.ac.cn ; zhangxuejin@sibs.ac.cn ; ouyangqi823@sohu.com ; xiao_lin_1985@hotmail.com ; shiyu@umdnj.edu ; xjzhang@sibs.ac.cn
英文摘要	We recently reported that the expression of the synaptic form of acetylcholinesterase (AChE) is induced during apoptosis in various cell types in vitro. Here, we provide evidence to confirm that AChE is expressed during ischemia-reperfusion (I/R)-induced apoptosis in vivo. Renal I/R is a major cause of acute renal failure (ARF), resulting in injury and the eventual death of renal cells due to a combination of apoptosis and necrosis. Using AChE-deficient mice and AChE inhibitors, we investigated whether AChE deficiency or inhibition can protect against apoptosis caused by I/R in a murine kidney model. Unilateral clamping of renal pedicles for 90 min followed by reperfusion for 24 h caused significant renal dysfunction and injury. Both genetic AChE deficiency and chemical inhibition of AChE (provided by huperzine A, tacrine and donepezil) significantly reduced the biochemical and histological evidence of renal dysfunction following I/R. Activation of caspases-8, -9, -12, and -3 in vivo were prevented and associated with reduced levels of cell apoptosis and cell death. A further investigation also confirmed that AChE deficiency down-regulated p53 induction and phosphorylation at serine-15, and decreased the Bax/Bcl-2 ratio during I/R. In conclusion, our study demonstrates that AChE may be a pro-apoptotic factor and the inhibition of AChE reduces renal I/R injury. These findings suggest that AChE inhibitors may represent a therapeutic strategy for protection against ischemic acute renal failure.
学科主题	Biochemistry & Molecular Biology; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]	ENDOPLASMIC-RETICULUM STRESS ; CYTOCHROME-C RELEASE ; ACETYLCHOLINESTERASE EXPRESSION ; CELL-DEATH ; PC12 CELLS ; ACTIVATION ; PATHWAY ; BIS(7)-TACRINE ; ER ; NEUROPROTECTION
收录类别	SCI
语种	英语
WOS记录号	WOS:000276046700007
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/992]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Ye, WY,Gong, XW,Xie, J,et al. AChE deficiency or inhibition decreases apoptosis and p53 expression and protects renal function after ischemia/reperfusion[J]. APOPTOSIS,2010,15(4):474-487.
APA	Ye, WY.,Gong, XW.,Xie, J.,Wu, J.,Zhang, XJ.,...&Zhang, XJ.(2010).AChE deficiency or inhibition decreases apoptosis and p53 expression and protects renal function after ischemia/reperfusion.APOPTOSIS,15(4),474-487.
MLA	Ye, WY,et al."AChE deficiency or inhibition decreases apoptosis and p53 expression and protects renal function after ischemia/reperfusion".APOPTOSIS 15.4(2010):474-487.