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The Effect of Alpha-Tocopherol on Viability of PC12 Cells during Oxidative Stress and Expression of Genes Encoding Pro- and Anti-Apoptotic Mitochondrial Proteins, SOD2 and Transcription Factors NRF-1, NRF-2 and TFAM
Journal of Evolutionary Biochemistry and Physiology ( IF 0.6 ) Pub Date : 2020-05-01 , DOI: 10.1134/s0022093020030084
I. O. Zakharova , A. O. Akhmetshina , L. V. Bayunova , L. R. Kizhaeva , N. F. Avrova

Abstract Long-term (18 h) preincubation with an antioxidant alpha-tocopherol (alpha-T) both at micromolar and nanomolar concentrations was shown to increase the viability of the PC12 neuronal cell line exposed to oxidative stress, while during short-term preincubation (30 min) alpha-T exhibited a protective effect only at micrimolar concentrations. Using real-time polymerase chain reaction (RT-PCR), it was demonstrated that exposure of PC12 cells to a pro-oxidant hydrogen peroxide increases expression of a proapoptotic mitochondrial protein Bax to a larger extent than that of a antiapoptotic protein Bcl-xL. In contrast, preincubation of PC12 cells with alpha-T before exposure to hydrogen peroxide increased Bcl-xL expression but did not influence Bax expression. Hence, it appears that alpha-T promotes normalization of the Bax/Bcl-xL ratio increased due to the prooxidant’s effect. In control PC12 cells, alpha-T significantly increased expression of the transcription factors NRF-2 and TFAM, but not NRF-1, which perform varied functions and, specifically, can activate mitochondrial biogenesis. In addition, alpha-T decreased the Bax/Bcl-xL ratio in PC12 cells, as shown by immunoblotting. At the same time, both exposure to hydrogen peroxide and preincubation with alpha-T caused no significant changes in NRF-1, NRF-2 and TFAM expression in PC12 cells. Preincubation of PC2 cells with alpha-T before exposure to hydrogen peroxide evoked earlier expression of an antiapoptotic enzyme superoxide dismutase 2 (SOD2) than when the prooxidant acted alone. Thus, it appears that normalization of the Bax/Bcl-xl ratio and a relatively early increase in SOD2 expression contribute to the protective effect of alpha-T towards PC12 cells during oxidative stress. The fact that alpha-T increases NRF-2 and TFAM expression in control PC12 cells suggests that alpha-T can slightly boost mitochondrial biogenesis. However, under oxidative stress conditions, which are characterized by a deficiency of macroergic compounds, no evidence for the alpha-T-induced activation of such an energy-consuming process as mitochondrial biogenesis in PC12 cells was found.

中文翻译:

α-生育酚对氧化应激期间 PC12 细胞活力和编码促凋亡和抗凋亡线粒体蛋白、SOD2 和转录因子 NRF-1、NRF-2 和 TFAM 的基因表达的影响

摘要 使用微摩尔和纳摩尔浓度的抗氧化剂 α-生育酚 (alpha-T) 进行长期 (18 小时) 预孵育显示出增加暴露于氧化应激的 PC12 神经元细胞系的活力,而在短期预孵育期间。 30 分钟) α-T 仅在微摩尔浓度下表现出保护作用。使用实时聚合酶链反应 (RT-PCR),证明 PC12 细胞暴露于促氧化剂过氧化氢中,比抗凋亡蛋白 Bcl-xL 更大程度地增加了促凋亡线粒体蛋白 Bax 的表达。相比之下,在暴露于过氧化氢之前用 alpha-T 预培养 PC12 细胞会增加 Bcl-xL 的表达,但不影响 Bax 的表达。因此,由于促氧化剂的作用,似乎 alpha-T 促进了 Bax/Bcl-xL 比率的正常化。在对照 PC12 细胞中,α-T 显着增加转录因子 NRF-2 和 TFAM 的表达,但不增加 NRF-1 的表达,NRF-1 具有多种功能,特别是可以激活线粒体生物发生。此外,如免疫印迹所示,α-T 降低了 PC12 细胞中的 Bax/Bcl-xL 比率。同时,暴露于过氧化氢和预孵育 alpha-T 均未引起 PC12 细胞中 NRF-1、NRF-2 和 TFAM 表达的显着变化。与促氧化剂单独作用相比,在暴露于过氧化氢之前用 α-T 预培养 PC2 细胞会引起抗凋亡酶超氧化物歧化酶 2 (SOD2) 的更早表达。因此,似乎 Bax/Bcl-xl 比率的正常化和 SOD2 表达的相对早期增加有助于 α-T 在氧化应激期间对 PC12 细胞的保护作用。α-T 增加对照 PC12 细胞中 NRF-2 和 TFAM 表达的事实表明,α-T 可以略微促进线粒体生物发生。然而,在氧化应激条件下,其特征是缺乏巨能化合物,没有证据表明 α-T 诱导激活这种耗能过程,如 PC12 细胞中的线粒体生物发生。α-T 增加对照 PC12 细胞中 NRF-2 和 TFAM 表达的事实表明,α-T 可以略微促进线粒体生物发生。然而,在氧化应激条件下,其特征是缺乏巨能化合物,没有证据表明 α-T 诱导激活这种耗能过程,如 PC12 细胞中的线粒体生物发生。α-T 增加对照 PC12 细胞中 NRF-2 和 TFAM 表达的事实表明,α-T 可以略微促进线粒体生物发生。然而,在氧化应激条件下,其特征是缺乏巨能化合物,没有证据表明 α-T 诱导激活这种耗能过程,如 PC12 细胞中的线粒体生物发生。
更新日期:2020-05-01
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