Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats
文献类型：期刊论文
| 作者 | Wang, Yizheng ; Yao, Hailan
|
| 刊名 | JOURNAL OF CLINICAL INVESTIGATION
 |
| 出版日期 | 2010 |
| 卷号 | 120期号:10页码:3480-3492 |
| 关键词 | RECEPTOR POTENTIAL CHANNELS CALCIUM-ACTIVATED PROTEASE CEREBRAL-ARTERY OCCLUSION ELEMENT-BINDING PROTEIN NEURONAL DEATH CALPAIN-I CATION CHANNELS HUMAN HOMOLOG STROKE GROWTH |
| ISSN号 | 0021-9738 |
| 通讯作者 | 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 |
| 英文摘要 | 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. |
| 学科主题 | Research & Experimental Medicine |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation (NNSF) of China[2006CB806600, 2011CB809005, KSCX2-YW-R-099, 30711120566] |
| 语种 | 英语 |
| 公开日期 | 2012-07-13 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/1571]  |
| 专题 | 上海神经科学研究所_神经所(总) 上海神经科学研究所_神经信号转导研究组 |
| 推荐引用方式 GB/T 7714 | Wang, Yizheng,Yao, Hailan. Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats[J]. JOURNAL OF CLINICAL INVESTIGATION,2010,120(10):3480-3492. |
| APA | Wang, Yizheng,&Yao, Hailan.(2010).Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats.JOURNAL OF CLINICAL INVESTIGATION,120(10),3480-3492. |
| MLA | Wang, Yizheng,et al."Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats".JOURNAL OF CLINICAL INVESTIGATION 120.10(2010):3480-3492. |
入库方式： OAI收割
来源：上海神经科学研究所
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