Study Of The Biological Effects By Two GPx Mimics

GPx is well-known antioxidant selenoenzymes in organisms which destroy several harmful hydroperoxides and then maintain the metabolic balance of ROS in vivo, thus protecting the biomembranes and other cellular components from oxidative damage. ROS-related diseases include reperfusion injury, inflammatory process, age-related diseases, keshan disease, cancer and cataract. Therefore, GPx can really act as antioxidant drugs. We select supramolecular host molecules—cyclodextrins as the scaffolds of enzyme models, on the basis of structural understanding for GPx, obtain systems of cyclodextrin-based GPx models—2-SeCD and 2-TeCD.1 Study of the antitumor activity of 2-SeCD2-selenium-bridgedβ-cyclodextrin (2-SeCD) is a glutathione peroxidase mimic. It catalyzing the reduction of H2O2 with GSH and its GPx activity is 7.4 U/μmol. In the study of biological activities of 2-SeCD in our lab previously, we found low dose of 2-SeCD could inhibit the UV-B induced cell injury and inhibit cell apoptosis, but the effects of high dose of 2-SeCD have not been reported. Here, we have studied the effects of low and high dose 2-SeCD on HeLa cells proliferation and. death We found low dose of 2-SeCD could inhibit HeLa cell apoptosis. It can protect cells against oxidative damage and antiapoptotic mechanism may be its antioxidant ability. High dose of 2-SeCD can induce HeLa cells apoptosis. The apoptotic mechanism may be that it can largely and rapidly deplete GSH, activate caspase-3 and directly induced the HeLa cell apoptosis. The results showed the dual effect of 2-SeCD on HeLa cells growth, which has great potential in the tumor treatment.2 Study of the UV-B induced thymocytes apoptosis blocked by 2-TeCDWe construct the UV-B induced thymocytes of BALB/c mice damage model system, demonstrate the damaged thymocytes have great changes. It was found that UV-B could induce cell apoptosis and change cell cycle progression. After exposure to 100 J/m2 of UV-B, pre-G1 phase thymocytes were increased significantly and S phase thymocytes were decreased significantly. UV-B could also induce lipid peroxidation of thymocytes to have their MDA amount increased. These phenomena could be explained by production of reactive oxygen species (ROS), which were induced by UV-B radiation. In this study, we examined the protective effect of dicyclodextrinyl ditelluride (2-TeCD), the glutathione peroxidase (GPx, EC 1.11.1.9) mimics, on thymocytes apoptosis induced by UV-B radiation. The experimental results showed that 2-TeCD protects thymocytes from apoptosis. Moreover,2-TeCD inhibits lipid peroxidation of thymocytes and displayed great antioxidant ability. Furthermore,2-TeCD blocks the accumulation of wild-type-p53 (wt-p53) tumor-suppressor gene product caused by UV-B radiation. Therefore, this is a kind of promising antioxidant drug, which protect skin cell from UV-induced phototo.