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Induction of foxo3a protects turtle neurons against oxidative stress.
Comparative Biochemistry and Physiology A: Molecular & Integrative Physiology ( IF 2.3 ) Pub Date : 2020-02-08 , DOI: 10.1016/j.cbpa.2020.110671
Melissa Reiterer 1 , Sarah L Milton 1
Affiliation  

The detrimental effects of oxidative stress caused by the accumulation of Reactive Oxygen Species (ROS) factor into aging, senescence and several neurodegenerative diseases. Mammalian models are extremely susceptible to the stresses that follow the restoration of oxygen after anoxia; however some organisms including the freshwater turtle Trachemys scripta can withstand extended anoxia and reoxygenation without apparent pathology. The ability of the turtle to withstand these conditions is thought to be linked to the upregulation of protective mechanisms such as heat shock proteins (HSP) as well as the suppression of ROS formation and the upregulation of antioxidant defenses. One such antioxidant mechanism is the transcription factor Forkhead box O3a (FOXO3a), that has been shown to be activated in several animal models during oxidative stress. In this study, we utilized both the transfection of a plasmid carrying foxo3a and the pharmacological manipulation of foxo3a using the green tea extract Epigallocatechin-3-gallate (EGCG) to investigate the protective role of FOXO3a in the turtle brain. Our studies found that transcript levels of foxo3a were upregulated significantly during reoxygenation with greater increases during chemical oxidative stress. Induction of foxo3a by direct transfection significantly decreased cell death during chemical oxidative stress. Cells treated with EGCG also showed increased foxo3a expression and decreased cell death in the presence of H2O2. These results agree with results seen in other animal models and suggest that EGCG (through the upregulation of foxo3a) may be a therapeutic target against oxidative stress damage that warrants further investigation.

中文翻译:

foxo3a 的诱导保护龟神经元免受氧化应激。

由活性氧 (ROS) 因子积累引起的氧化应激对衰老、衰老和几种神经退行性疾病的有害影响。哺乳动物模型对缺氧后氧气恢复后的压力极为敏感;然而,包括淡水龟 Trachemys scripta 在内的一些生物可以承受长时间的缺氧和复氧而没有明显的病理。海龟承受这些条件的能力被认为与热休克蛋白 (HSP) 等保护机制的上调以及 ROS 形成的抑制和抗氧化防御的上调有关。一种这样的抗氧化机制是转录因子 Forkhead box O3a (FOXO3a),它已被证明在氧化应激期间在几种动物模型中被激活。在这项研究中,我们利用携带 foxo3a 的质粒的转染和使用绿茶提取物 Epigallocatechin-3-gallate (EGCG) 对 foxo3a 的药理操作来研究 FOXO3a 在龟脑中的保护作用。我们的研究发现,在再氧化过程中,foxo3a 的转录水平显着上调,而在化学氧化应激过程中增加幅度更大。通过直接转染诱导foxo3a 显着减少化学氧化应激期间的细胞死亡。在 H2O2 存在下,用 EGCG 处理的细胞也显示出 foxo3a 表达增加和细胞死亡减少。这些结果与在其他动物模型中看到的结果一致,并表明 EGCG(通过 foxo3a 的上调)可能是抗氧化应激损伤的治疗靶点,值得进一步研究。
更新日期:2020-02-10
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