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Redox state and biomolecular mechanism underlying the oxidative vulnerability of neonatal isolation model

新生儿隔离模型氧化脆弱性的氧化还原状态和生物分子机制

基本信息

批准号：
18591297
负责人：
UEDA Yuto
金额：
$ 2.42万
依托单位：
University of Miyazaki
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591297/
关键词：
Glutamate Redox GABA Neonatal isolation kindling

项目摘要

Nitroxide radical has been reported to react with hydroxyl radical and superoxide anion radical in the presence of cysteine or NADH. In this report the EPR SI of nitroxide radicals did not decay exponentially in the reaction with other radicals. The signal decay in this reaction is in accord with a linear function. On the other hand, its EPR SI decayed exponentially in the reaction with the reductants. Therefore, the reaction dynamics of nitroxide radicals with the reductants differed from that with other radicals. In the present study, the EPR SI of hydroxymethyl-PROXYL decayed exponentially. Therefore, the shortening of the halflife in the NI group without acute stress does not arise due to the reaction of nitroxide radical to other radicals (such as superoxide radical and hydroxyl radical). This indicates the enhancement of reducing ability. Therefore, the results obtained in this study indicate that while the intracerebral reducing ability was significantly depleted by acute stress in the NI group, this depletion did not occur in the control rats. It was also found that the intracerebral reducing ability significantly increased in the rats that had been subjected to NI when the acute stress was not applied. It is thought that the in vivo reducing ability is decreased due to mitochondrial damage, and a previous study reported that immobilization stress induced mitochondrial dysfunction. Therefore, the depletion of the intracerebral reducing ability after immobilization in the NI group may be related to mitochondrial damage in the brain. However, interpretation of the mechanisms behind the enhancement of intracerebral reducing ability in the NI group without the acute stress is now under way. We believe that impairment of the intracerebral reducing ability caused by acute stress in the NI rats is important biological evidence of cerebral vulnerability to acute stress in this model.

据报道，在半胱氨酸或NADH存在的情况下，氮氧化物自由基与羟基自由基和超氧阴离子自由基发生反应。在本报告中，氮氧自由基的EPR SI在与其他自由基的反应中没有呈指数衰减。该反应的信号衰减符合线性函数。另一方面，它的EPR SI在与还原剂的反应中呈指数衰减。因此，氮氧化物自由基与还原剂的反应动力学不同于与其他自由基的反应动力学。在本研究中，羟甲基- proxyl的EPR SI呈指数衰减。因此，在没有急性应激的NI组中，半衰期缩短并不是因为氮氧化物自由基与其他自由基（如超氧自由基和羟基自由基）发生反应而产生的。这表明还原能力增强。因此，本研究结果表明，急性应激使NI组的脑内还原能力明显降低，而对照大鼠没有发生这种降低。我们还发现，在不施加急性应激的情况下，NI大鼠的脑内还原能力显著增加。据认为，体内还原能力的下降是由于线粒体损伤，已有研究报道固定化应激诱导线粒体功能障碍。因此，NI组固定后脑内还原能力的减弱可能与脑内线粒体损伤有关。然而，在没有急性应激的情况下，NI组脑内还原能力增强背后的机制正在解释中。我们认为，急性应激对NI大鼠脑内还原能力的损害是该模型大脑急性应激易感性的重要生物学证据。