Department of Biological Sciences, Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton, FL 33431, USA.
Comp Biochem Physiol A Mol Integr Physiol. 2020 May;243:110671. doi: 10.1016/j.cbpa.2020.110671. Epub 2020 Feb 8.
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 HO. 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.
活性氧（ROS）的积累导致氧化应激，这种应激作用会导致衰老、衰老和几种神经退行性疾病。哺乳动物模型对缺氧后氧气恢复引起的应激非常敏感；然而，包括淡水龟 Trachemys scripta 在内的一些生物可以在没有明显病理学的情况下耐受长时间的缺氧和再氧化。人们认为，海龟能够耐受这些条件与其上调保护机制有关，如热休克蛋白（HSP），以及抑制 ROS 形成和上调抗氧化防御。一种抗氧化机制是转录因子叉头框 O3a（FOXO3a），在几种动物模型的氧化应激中已被证明被激活。在这项研究中，我们利用转染携带 foxo3a 的质粒和使用绿茶提取物表没食子儿茶素没食子酸酯（EGCG）对 foxo3a 的药理操作，研究了 FOXO3a 在龟脑中的保护作用。我们的研究发现，foxo3a 的转录水平在再氧化过程中显著上调，在化学氧化应激过程中上调更为明显。直接转染诱导 foxo3a 显著降低了化学氧化应激过程中的细胞死亡。在存在 HO 的情况下，用 EGCG 处理的细胞也表现出 foxo3a 表达增加和细胞死亡减少。这些结果与其他动物模型的结果一致，表明 EGCG（通过上调 foxo3a）可能是一种针对氧化应激损伤的治疗靶点，值得进一步研究。
