Two free radical pathways mediate chemical hypoxia-induced glutamate release in synaptosomes from the prefrontal cortex.
Two free radical pathways mediate chemical hypoxia-induced glutamate release in synaptosomes from the prefrontal cortex.
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DOI：
10.1016/j.bbamcr.2011.10.004
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发表时间：
2012-02
期刊：
影响因子：
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通讯作者：
Yi Dong;Wen Zhang;B. Lai;Wenjie Luan;Yanhua Zhu;Bing-Qiao Zhao;P. Zheng
中科院分区：
文献类型：
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作者：
Yi Dong;Wen Zhang;B. Lai;Wenjie Luan;Yanhua Zhu;Bing-Qiao Zhao;P. Zheng
线粒体细胞色素c氧化酶的抑制是缺氧条件下最早发生的事件之一，这种抑制可导致神经元损伤。因此，细胞色素c氧化酶抑制剂氰化钠（NaCN）被广泛用于通过抑制这种酶来产生化学缺氧模型。然而，抑制细胞色素c氧化酶的下游信号通路仍有待研究。在本文中，我们使用氰化钠模拟线粒体细胞色素c氧化酶的抑制，并研究其对谷氨酸释放的突触体从前额皮质使用在线荧光法的影响。我们还进一步研究了潜在的机制，氰化钠对谷氨酸释放的增强作用，使用药理学方法结合其他技术。结果表明，氰化钠可显著增加前额叶皮层突触体谷氨酸的释放，广谱自由基清除剂MnTBAP和褪黑素可完全消除氰化钠对谷氨酸释放的影响，其中H_2O_2-NMDA受体途径介导了一部分，脂质过氧自由基-ATP合成酶途径介导了另一部分;清除H2O2和提高ATP合成酶活性可完全抑制氰化钠诱导的谷氨酸释放。
It has been known that the inhibition of mitochondrial cytochrome c oxidase is one of the earliest events occurring under hypoxia and this inhibition can lead to neuronal damages. Thus, the cytochrome c oxidase inhibitor sodium cyanide (NaCN) is widely used to produce a model of chemical hypoxia by inhibiting this enzyme. However, the downstream signaling pathways of the inhibition of the cytochrome c oxidase remain to be studied. In the present paper, we used sodium cyanide to mimic the inhibition of the mitochondrial cytochrome c oxidase and studied its effect on glutamate release in synaptosomes from the prefrontal cortex using on-line fluorimetry. We also further investigated the mechanisms underlying the enhancing effect of sodium cyanide on glutamate release using pharmacological approaches combined with other techniques. The results showed that sodium cyanide significantly increased glutamate release from synaptosomes of prefrontal cortex; the broad-spectrum free radical scavenger MnTBAP and melatonin completely abolished the effect of sodium cyanide on glutamate release; the H2O2–NMDA receptor pathway mediated one part, whereas the lipid peroxyl radicals-ATP synthase pathway mediated another part of the sodium cyanide-induced glutamate release; scavenging H2O2and enhancing ATP synthase activity could completely abolish the sodium cyanide-induced glutamate release.