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

点击翻译按钮获取中文摘要

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.