Excitotoxic insults lead to peroxiredoxin hyperoxidation.
Excitotoxic insults lead to peroxiredoxin hyperoxidation.
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DOI：
10.4161/oxim.2.2.8300
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发表时间：
2009-04
影响因子：
--
通讯作者：
Hardingham GE
中科院分区：
文献类型：
--
作者：
Léveillé F;Soriano FX;Papadia S;Hardingham GE
有丝分裂后的神经元必须具有强大的抗氧化防御能力才能在生物体的寿命中存活下来。我们最近发现神经元的抗氧化防御是由突触活动增强的。通过N-甲基-D-天冬氨酸（NMDA）受体起作用的突触活性升高，可增强硫氧还蛋白活性，促进过氧化的过氧化物酶的还原，并促进对氧化应激的抵抗。相反，自发突触NMDA受体活性的阻断使神经元对氧化损伤引起的过氧化物氧还蛋白过氧化反应高度敏感。这些NMDA受体依赖性效应部分由以硫氧还蛋白-过氧化物氧还蛋白系统为中心的基因表达变化的协调程序介导，硫氧还蛋白-过氧化物氧还蛋白系统是一种基于巯基的酶系统，是氧化应激源（如氢过氧化物）的重要还原剂。我们在这里表明，虽然太少的多巴胺能活动可以使神经元容易受到过氧化物酶过氧化，所以可以太多。神经元暴露于毒性浓度的谷氨酸，激活突触和突触外NMDA受体，急性诱导过氧化物氧还蛋白过氧化。因此，NMDA受体活性对神经元过氧化物酶活性的影响遵循经典的U形剂量反应曲线。
Post-mitotic neurons must have strong antioxidant defenses to survive the lifespan of the organism. We recently showed that neuronal antioxidant defenses are boosted by synaptic activity. Elevated synaptic activity, acting via the N-methyl-D-aspartate (NMDA) receptor, enhances thioredoxin activity, facilitates the reduction of hyperoxidized peroxiredoxins, and promotes resistance to oxidative stress. In contrast, blockade of spontaneous synaptic NMDA receptor activity renders neurons highly sensitive to hyperoxidation of peroxiredoxins by oxidative insults. These NMDA receptor-dependent effects are mediated in part by a coordinated program of gene expression changes centered on the thioredoxin-peroxiredoxin system, a thiol-based enzymatic system which is an important reducer of oxidative stressors such as hydroperoxides. We show here that while too little glutamatergic activity can render neurons vulnerable to peroxiredoxin hyperoxidation, so can too much. Exposure of neurons to toxic concentrations of glutamate, activating both synaptic and extrasynaptic NMDA receptors, acutely induces peroxiredoxin hyperoxidation. Thus, the effect of NMDA receptor activity on the activity of neuronal peroxiredoxins follows the classical U-shaped dose response curve.
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影响因子：
5.3
作者：
Soriano, Francesc X.;Martel, Marc-Andre;Papadia, Sofia;Vaslin, Anne;Baxter, Paul;Rickman, Colin;Forder, Joan;Tymianski, Michael;Duncan, Rory;Aarts, Michelle;Clarke, Peter;Wyllie, David J. A.;Hardingham, Giles E.
通讯作者：
Hardingham, Giles E.
影响因子：
25
作者：
通讯作者：
--
影响因子：
5.3
作者：
Soriano, Francesc X;Papadia, Sofia;Hofmann, Frank;Hardingham, Neil R;Bading, Hilmar;Hardingham, Giles E
通讯作者：
Hardingham, Giles E
DOI：
10.1196/annals.1323.002
发表时间：
2005-01-01
期刊：
LONGEVITY HEALTH SCIENCES: THE PHOENIX CONFERENCE
影响因子：
--
作者：
Yoshida, T;Nakamura, H;Yodoi, J
通讯作者：
Yodoi, J
影响因子：
5.6
作者：
Aarts, MM;Tymianski, M
通讯作者：
Tymianski, M