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首页> 外文期刊>Neurochemical research >Protein vicinal thiol oxidations in the healthy brain: Not so radical links between physiological oxidative stress and neural cell activities
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Protein vicinal thiol oxidations in the healthy brain: Not so radical links between physiological oxidative stress and neural cell activities

机译:健康大脑中的蛋白质邻位硫醇氧化:生理氧化应激与神经细胞活动之间的自由基联系并非如此

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摘要

Reversible oxidations of protein thiols have emerged as alternatives to free radical-mediated oxidative damage with which to consider the impacts of oxidative stress on cellular activities but the scope and pathways of such oxidations in tissues, including the brain, have yet to be fully defined. We report here a characterization of reversible oxidations of glutathione and protein thiols in extracts from rat brains, from two sources, which had been (1) frozen quickly after euthanasia to preserve in vivo redox states and (2) subjected to alkylation upon tissue disruption to trap reduced thiols. Brains were defined, relatively, as Reduced and Moderately Oxidized based on measured ratios of reduced (GSH) to oxidized (GSSG) glutathione. Levels of protein disulfides formed by the cross-linking of closely-spaced (vicinal) protein thiols, but not protein S-glutathionylation, were higher in extracts from the Moderately Oxidized brains compared to the Reduced brains. Moreover, the oxidized vicinal thiol proteome contains proteins that impact cellular energetics, signaling, neurotransmission, and cytoskeletal dynamics among others. These findings argue that kinetically-competent pathways for reversible, two-electron oxidations, of protein vicinal thiols can be activated in healthy brains in response to physiological oxidative stresses. We propose that such oxidations may link oxidative stress to adaptive, but also potentially deleterious, changes in neural cell activities in otherwise healthy brains.
机译:蛋白质硫醇的可逆氧化已成为自由基介导的氧化损伤的替代方法,可以考虑氧化应激对细胞活动的影响,但这种氧化在组织(包括大脑)中的范围和途径尚未完全定义。我们在此报告了两种来源的大鼠脑提取物中谷胱甘肽和蛋白质硫醇可逆氧化的表征,这些来源已被(1)安乐死后迅速冷冻以保留体内氧化还原状态,并且(2)在组织破坏后发生烷基化捕获还原的硫醇。相对地,根据测得的还原型(GSH)与氧化型(GSSG)谷胱甘肽的比例,将大脑定义为还原和中度氧化。与中等程度氧化的大脑相比,中度氧化大脑提取物中通过紧密间隔的(邻位)蛋白质硫醇交联而形成的蛋白质二硫化物水平更高,而蛋白质S-谷胱甘肽化则不是。此外,氧化的邻位硫醇蛋白质组包含的蛋白质会影响细胞的能量,信号传导,神经传递和细胞骨架动力学等。这些发现表明,在健康的大脑中,响应生理氧化应激,可以激活蛋白质邻位硫醇的可逆性双电子氧化的动力学功能途径。我们提出,这种氧化可以将氧化应激与其他健康大脑中神经细胞活动的适应性变化(但也可能有害)联系起来。

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