Msr介导肉鸡砷毒性氧化应激与蛋白修复机制研究

中文摘要

英文摘要

Exposure or excessive absorption of arsenic can cause a variety of diseases and pathological damage. Currently, oxidative stress mechanism is the research focus on arsenic toxicity. The theory suggests that oxidative damage of macromolecules by ROS plays a major role in arsenic toxicity. Methionine sulfoxide reductase (Msr) is an important enzyme, which is directly or indirectly involved in the repair of oxidized proteins and regulation of reactive oxygen species (ROS) metabolism. Possibly, Msr play a role in regulating the oxidative stress caused by arsenic toxicity. Unfortunately, no related researches are reported. The project is to investigate the possible role of Msr in regulating oxidative stress and protein oxidation caused by arsenic in chicken. The main contents are as follows: 1) the characteristics of protein oxidation caused by arsenic toxicity;2) the characteristics of Msr gene and Msr protein expression; 3) target proteins of Msr and its regulation on the target proteins; 4)the repair of methionine sulfoxide in protein and regulation of ROS metabolism by Msr. Different from traditional antioxidant theory, the project is to elucidate the mechanism of arsenic toxicity and detoxification from the perspective of the repair of oxidized proteins and regulation of ROS metabolism by Msr, which will provide theoretical knowledge for the development of detoxification techniques.

结题摘要

砷暴露或过量吸收能导致多种疾病和病理损伤。目前氧化应激机制是砷毒性的研究热点，该理论认为ROS引起的生物大分子氧化损伤在砷毒性中起主要作用。Msr（甲硫氨酸亚砜还原酶）是生物体内重要的氧化还原调节器，直接或间接参与氧化蛋白的修复和活性氧代谢调节，可能在砷导致的氧化应激毒性中起调控作用，但目前未有这方面报道。本项目以肉鸡活体和肝细胞为对象，研究Msr介导的蛋白氧化修复和ROS调节在肉鸡砷毒性调控中的作用，主要内容包括：1）砷中毒介导的蛋白氧化（特别是蛋白质甲硫氨酸亚砜化）特性；2）Msr基因及蛋白表达特性；3）Msr蛋白特性、靶标蛋白及对靶标蛋白的调节作用；4）Msr对蛋白质甲硫氨酸亚砜修复和ROS代谢的调节作用。获得的重要结果如下：1）建立了肉鸡肝细胞水平和活体的三氧化二砷中毒模型。２）评价了不同浓度三氧化二砷中毒情况下肉鸡肝细胞和肝组织中氧化还原状态和活性的调控机制。3）检测了不同浓度三氧化二砷作用下肝细胞及肝组织中Msr基因的表达及蛋白的表达。4）合并应用ＮＡＣ（氧化应激保护剂）和三氧化二砷评价Ｍsr对蛋白质甲硫氨酸亚砜修复和对ＲＯＳ代谢的调节作用。　不同于传统的抗氧化理论，本项目从Msr对氧化应激后氧化蛋白修复和活性氧代谢调控的角度,阐明了肉鸡砷中毒的毒性机理和解毒作用机制。本项目发表SCI收录论文3篇，中文一级刊物论文2篇；硕士3名。