Oxidative Damage Mechanism Of Cadmium To Yeast Cell

With the development of industry, heavy metals are widely used and released into the environment. These metals are difficult to be degraded biochemically, and thus threaten the health of human beings through the food chains. Therefore, increasing attention has been paid worldwide to heavy metal pollution problems. Cadmium is a highly toxic metal and easily accumulated in various mammalian cells through the food chains. Its half-life is10to30years. The chronic accumulation of cadmium induces a series of injuries on organisms such as kidney, lung, liver, testis, brain, bones and blood system. Therefore, it is important to investigate the damage mechanisms of cadmium in order to provide the theory basis for its pollution control.Saccharomyces cerevisiae is a good model organism. The study of cadmium effect on S.cerevisiae will provide very useful information for the understanding of its action mechanism to other eukayrotes. In this paper, by screening the essential gene overexpression pool of Saccharomyces cerevisiae, we found six response genes after cadmium treatment,including OLE1,PRP16,PCL8,MRS6,NOP1and RTP1. Among them,the overexpression of OLE1can enhance the resistance of yeast to cadmium. The OLE1gene could encodes Delta(9) fatty acid desaturase to produce monounsaturated fatty acids.The analysis of RT-PCR and membrane lipid composition show that cadmium ions can induce high expression of OLE1gene in wild (By4741) and mutant (mga2â–³) yeast cells and result in an increase in intracellular content of monounsaturated fatty acids. The overexpression of OLE1can increase the intracellular content of monounsaturated fatty acids. Similar to ascorbic acid, it can enhance the resistance to cadmium and decrease the intracellular content of ROS, MDA and carbonyl protein.The result of further biochemical studies showed that ROS content was increased significantly, while cell growth was inhibited after cadmium treatment. Moreover cadmium could decrease the activities of SOD/CAT/Gpx and increase contents of MDA and carbonyl protein. Exogenous ascorbic acid or endogenous glutathione (GSH) could increase cell activity,resist to cadmium in Cd-stressed Saccharomyces cerevisiae treated with cadmium, reduce the degree of oxidative damage of cadmium stress on yeast cells and restor the activity of antioxidant to some extent. Different from ascorbic acid, the overexpression of OLE1can not affect the activities of antioxidative enzymes.The overexpression of OLE1can also enhance the resistance of yeast to other metals like copper, hexavalent chromium and trivalent chromium, which performed the similar response mechanism in yeast treated with cadmium. It indicates that the oxidative damage of a variety of heavy metal ions to cell membrane system is a conserved mechanism of cytotoxicity and the overexpression of OLE1can enhance the resistance of cells to metals.