中国科学院上海生命科学研究院神经科学研究所机构知识库
Advanced  
SIBS OpenIR  > 神经所(总)  > 期刊论文
Title: Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats
Author: Du, Wanlu ; Huang, Junbo ; null(王以政) ; Zhou, Kechun ; Duan, Bo ; null(王以政)
Source: JOURNAL OF CLINICAL INVESTIGATION
Issued Date: 2010
Volume: 120, Issue:10, Pages:3480-3492
Keyword: RECEPTOR POTENTIAL CHANNELS ; CALCIUM-ACTIVATED PROTEASE ; CEREBRAL-ARTERY OCCLUSION ; ELEMENT-BINDING PROTEIN ; NEURONAL DEATH ; CALPAIN-I ; CATION CHANNELS ; HUMAN HOMOLOG ; STROKE ; GROWTH
Subject: Research & Experimental Medicine
Corresponding Author: Wang, YZ (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Neurosci, Lab Neural Signal Transduct,Inst Neurosci,Grad Sc, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,yzwang@ion.ac.cn
English Abstract: Brain injury after focal cerebral ischemia, the most common cause of stroke, develops from a series of pathological processes, including excitotoxicity, inflammation, and apoptosis. While NMDA receptors have been implicated in excitotoxicity, attempts to prevent ischemic brain damage by blocking NMDA receptors have been disappointing. Disruption of neuroprotective pathways may be another avenue responsible for ischemic damage, and thus preservation of neuronal survival may be important for prevention of ischemic brain injury. Here, we report that suppression of proteolytic degradation of transient receptor potential canonical 6 (TRPC6) prevented ischemic neuronal cell death in a rat model of stroke. The TRPC6 protein level in neurons was greatly reduced in ischemia via NMDA receptor-dependent calpain proteolysis of the N-terminal domain of TRPC6 at Lys(16). This downregulation was specific for TRPC6 and preceded neuronal death. In a rat model of ischemia, activating TRPC6 prevented neuronal death, while blocking TRPC6 increased sensitivity to ischemia. A fusion peptide derived from the calpain cleavage site in TRPC6 inhibited degradation of TRPC6, reduced infarct size, and improved behavioral performance measures via the cAMP response element-binding protein (CREB) signaling pathway. Thus, TRPC6 proteolysis contributed to ischemic neuronal cell death, and suppression of its degradation preserved neuronal survival and prevented ischemic brain damage.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1571
Appears in Collections:神经所(总)_期刊论文
神经信号转导研究组_期刊论文

Files in This Item: Download All
File Name/ File Size Content Type Version Access License
Du-2010-Inhibition of TRPC6.pdf(7903KB)----开放获取View Download

Recommended Citation:
Du, Wanlu; Huang, Junbo; Yao, Hailan; Zhou, Kechun; Duan, Bo; Wang, Yizheng.Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats,JOURNAL OF CLINICAL INVESTIGATION,2010,120(10):3480-3492
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Du, Wanlu]'s Articles
[Huang, Junbo]'s Articles
[Yao, Hailan]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Du, Wanlu]‘s Articles
[Huang, Junbo]‘s Articles
[Yao, Hailan]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
文件名: Du-2010-Inhibition of TRPC6.pdf
格式: Adobe PDF
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!