College of Pharmaceutical Science, Jilin University, Changchun 130021, PR China.
College of Pharmaceutical Science, Jilin University, Changchun 130021, PR China; Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130000, PR China.
Int J Biol Macromol. 2021 Feb 15;170:503-513. doi: 10.1016/j.ijbiomac.2020.12.183. Epub 2020 Dec 28.
Glutathione peroxidase 1 (GPx1) is an important antioxidant selenium enzyme and has a good prospect for drug development. However, the expression of GPx1 requires a complex expression mechanism, which makes the drug development of recombinant GPx1 (rGPx1) difficult. In the previous study, we expressed highly active rhGPx1 in amber-less Escherichia coli by using a novel chimeric tRNA. However, the antioxidant effect of rhGPx1 at the cellular and animal levels has not been verified. In this study, we established isoproterenol (ISO)-induced oxidative stress injury models to study the antioxidant effect of rhGPx1 at the cellular and animal levels. Meanwhile, in order to more accurately reflect the antioxidant effect of rGPx1 in mice, we used the same method to express recombinant mouse GPx1 (rmGPx1) as a control for rhGPx1. The results of a study showed that rhGPx1 has a good antioxidant effect at the cellular and animal levels. However, due to species differences, rhGPx1 had immunogenicity in mice and antibodies of rhGPx1 could inhibit its antioxidant activity, so the antioxidant effect of rhGPx1 was not as good as rmGPx1 in mice. Nevertheless, this study provides a reliable theoretical basis for the development of rhGPx1 as an antioxidant drug.
谷胱甘肽过氧化物酶 1(GPx1)是一种重要的抗氧化硒酶,具有良好的药物开发前景。然而,GPx1 的表达需要复杂的表达机制,这使得重组 GPx1(rGPx1)的药物开发变得困难。在之前的研究中,我们使用新型嵌合 tRNA 在无琥珀终止密码子的大肠杆菌中表达了高活性 rhGPx1。然而,rhGPx1 在细胞和动物水平的抗氧化作用尚未得到验证。在本研究中,我们建立了异丙肾上腺素(ISO)诱导的氧化应激损伤模型,以研究 rhGPx1 在细胞和动物水平的抗氧化作用。同时,为了更准确地反映 rGPx1 在小鼠中的抗氧化作用,我们使用相同的方法表达重组小鼠 GPx1(rmGPx1)作为 rhGPx1 的对照。研究结果表明,rhGPx1 在细胞和动物水平均具有良好的抗氧化作用。然而,由于种属差异,rhGPx1 在小鼠中具有免疫原性,rhGPx1 的抗体可以抑制其抗氧化活性,因此 rhGPx1 在小鼠中的抗氧化作用不如 rmGPx1。尽管如此,这项研究为 rhGPx1 作为抗氧化药物的开发提供了可靠的理论基础。