期刊
NEUROBIOLOGY OF AGING
卷 24, 期 8, 页码 1123-1133出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2003.07.002
关键词
NMDA receptor; neuronal nitric oxide synthase; excitotoxic death; calcineurin; nitrotyrosine; phosphatase; kinase; TUNEL
资金
- NIA NIH HHS [R01 AG13620] Funding Source: Medline
- NIEHS NIH HHS [ES00260] Funding Source: Medline
- NINDS NIH HHS [NS 07457-04] Funding Source: Medline
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES000260] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG013620] Funding Source: NIH RePORTER
Stimulation of NMDA receptors activates neuronal nitric oxide synthase (nNOS) and the production of nitric oxide (NO). Dephosphorylation of nNOS increases nNOS enzymatic activity. We have examined the regulation of nNOS phosphorylation in rat cortical neurons following NMDA receptor activation. We show that nNOS is constitutively phosphorylated and that NMDA receptor activation decreases the level of nNOS phosphorylation by a mechanism that is blocked specifically by NMDA receptor antagonists and inhibitors of the Ca2+ regulated phosphatases calcineurin and PP1/PP2A. Using quantitative digital microscopy, we show that NMDA receptor activation induces the accumulation of nitrotyrosine, a measure of nNOS activity, and TdT-mediated fluorescein-dUTP nick end labeling (TUNEL) positivity, a measure of cell death. A calcineurin inhibitor blocked the increase in both TUNEL and nitrotyrosine positivity. Notably, TUNEL was increased in those neurons that were most strongly positive for nitrotyrosine. We conclude that NMDA receptor activation induces death of neurons by a cell autonomous pathway involving nNOS dephosphorylation by a calcineurin-dependent mechanism. (C) 2003 Elsevier lnc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据