Inhibition Of Intracellular SOD1by Several Chelators

Cu/Zn superoxide dismutase (SOD1) dismutates superoxide (O2·-) into molecular oxygen and hydrogen peroxide(H2O2), maintains the homeostasis of reactive oxygen species (ROS). NADPH oxidase (Nox) produce large amounts of O2·-in cells, SOD1results in a significant increase in the concentration of peroxide hydrogen. Peroxide hydrogen at the high levels can activated the aberrant redox signaling network or dysregulate the redox signaling network. This may be related to cancer and amyotrophic lateral sclerosis (ALS). At present, SOD1become an important targets in study of anticancer and ALS drugs.Our research group has synthesized a series of chelating agents. We investigate the impact of chelating agents on the SOD1activity in solution and cell through the method of Xanthine oxidase cytochrome C and HT Superoxide Dismutase Assay Kit, some of which has inhibitory effect. Then, we measure the level of cellular ROS by fluorescence probe DCFH-DA and DHE. Chelating agents and cell co-culture, intracellular H2O2levels measured by the flow cytometry is decreased obviously and O2levels increase.We screen some chelating agents, some of which has inhibitory effect on the activity of SOD1and alter the relative levels of intracellular superoxide and peroxide hydrogen. It is very vital significance for us to further study the SOD1inhibitors.