Regulation of antioxidant gene expression, oxidative stress resistance and ageing by peroxiredoxins

过氧化还原蛋白调节抗氧化基因表达、氧化应激抵抗和衰老

• 批准号: G0800082/1
• 负责人: Elizabeth Ann Veal
• 金额: $ 44.39万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0800082%2F1
• 关键词: Regulation; antioxidant; gene; expression; oxidative

Our cells are unavoidably exposed to harmful reactive oxygen species (ROS) which are produced as unwanted bi-products of normal metabolism. Exposure to sunlight, drugs and environmental chemicals, such as heavy metals, also lead to increased ROS-levels in cells. ROS cause cellular damage (oxidative stress) that is an important cause of ageing and of many diseases, such as cancer. Our cells contain protective antioxidant proteins which detoxify ROS, limiting this cellular damage. Oxidative stress stimulates the increased production of antioxidants. Peroxiredoxins are one such group of antioxidant proteins which protect against oxidative stress and have been shown to have roles in cancer. Peroxiredoxins are found in different tissues and have several different activities. Using genetic studies in the nematode worm Caenorhabditis elegans we will examine how peroxiredoxins in different tissues protect against oxidative stress and ageing. This work will also identify genes required for increasing antioxidant levels in response to oxidative stress. The power of genetic studies C.elegans to yield important insight into fundamental biological processes in humans is widely recognised. For example, two Nobel Prizes for Medicine have been recently awarded for advances made through studies in C.elegans. In addition to their genetic amenability, these worms have a number of features which make them ideally suited to our studies. For instance, their short lifespan of only a few weeks will allow us to rapidly determine whether genes we identify affect ageing. Indeed we will be able to examine whether these genes are involved in known lifespan-increasing mechanisms. Importantly, genes we identify are extremely likely to have counterparts in human which may be important in protecting against cancer, bacterial infections and ageing-associated diseases. Ultimately, these studies may suggest future strategies to manipulate levels of oxidative stress protective proteins that might be used to prevent ageing and age related diseases.

我们的细胞不可避免地暴露于有害的活性氧（ROS）中，这是正常代谢过程中产生的有害副产物。暴露在阳光、药物和环境化学物质（如重金属）下，也会导致细胞中ros水平升高。活性氧引起细胞损伤（氧化应激），这是衰老和许多疾病（如癌症）的重要原因。我们的细胞含有保护性抗氧化蛋白，可以解毒活性氧，限制细胞损伤。氧化应激刺激增加抗氧化剂的产生。过氧化物还毒素是一组抗氧化蛋白，它可以防止氧化应激，并已被证明在癌症中起作用。过氧化物还毒素存在于不同的组织中，有几种不同的活性。利用线虫秀丽隐杆线虫的遗传研究，我们将研究不同组织中的过氧化物氧化素如何防止氧化应激和衰老。这项工作还将确定在氧化应激反应中增加抗氧化水平所需的基因。遗传研究秀丽隐杆线虫对人类基本生物过程产生重要见解的力量已得到广泛认可。例如，最近有两项诺贝尔医学奖授予了对秀丽隐杆线虫研究取得的进展。除了它们的遗传适应性外，这些蠕虫还有许多特征，使它们非常适合我们的研究。例如，它们短短几周的寿命将使我们能够迅速确定我们所识别的基因是否会影响衰老。事实上，我们将能够检查这些基因是否与已知的寿命延长机制有关。重要的是，我们发现的基因极有可能在人类中有对应的基因，这可能对预防癌症、细菌感染和与衰老有关的疾病很重要。最终，这些研究可能会提出未来控制氧化应激保护蛋白水平的策略，这些蛋白可能被用来预防衰老和与年龄相关的疾病。