Tat-NR2B9c prevents excitotoxic neuronal superoxide production

被引：34

作者：

Chen, Yanting ^{[1
,2
]}

Brennan-Minnella, Angela M. ^{[2
]}

Sheth, Sunil ^{[2
]}

El-Benna, Jamel ^{[3
,4
]}

Swanson, Raymond A. ^{[2
]}

机构：

[1] Nanjing Univ, Sch Med, Drum Tower Hosp, Dept Neurol, Nanjing 210008, Jiangsu, Peoples R China

[2] Univ Calif San Francisco, Dept Neurol, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA

[3] CNRS, Ctr Rech Inflammat Paris, INSERM, U1149,ERL8252, Paris, France

[4] Univ Paris Diderot, Lab Excellence Inflamex, Sorbonne Paris Cite, Paris, France

来源：

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2015年 / 35卷 / 05期

基金：

美国国家卫生研究院;

关键词：

DNA damage; glutamate; ischemia; nitric oxide; oxidative stress; stroke; NMDA RECEPTOR; NITRIC-OXIDE; NADPH OXIDASE; ACTIVATION;

D O I：

10.1038/jcbfm.2015.16

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The Tat-NR2B9c peptide has shown clinical efficacy as a neuroprotective agent in acute stroke. Tat-NR2B9c is designed to prevent nitric oxide (NO) production by preventing postsynaptic density protein 95 (PSD-95) binding to N-methyl-D-aspartate (NMDA) receptors and neuronal nitric oxide synthase; however, PSD-95 is a scaffolding protein that also couples NMDA receptors to other downstream effects. Here, using neuronal cultures, we show that Tat-NR2B9c also prevents NMDA-induced activation of neuronal NADPH oxidase, thereby blocking superoxide production. Given that both superoxide and NO are required for excitotoxic injury, the neuroprotective effect of Tat-NR2B9c may alternatively be attributable to uncoupling neuronal NADPH oxidase from NMDA receptor activation.

引用

页码：739 / 742

页数：4

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