Effect of DPP3 expression on oxidative stress in MEFs

Dipeptidyl peptidase III (DPPIII), the sole member of the M49 family of metalloproteases, is a zinc-dependent aminopeptidase that specifically cleaves dipeptides at the N-terminus. DPPIII is mainly found as a cytosolic protein although some studies suggest a potential localization in membranes. DPPIII is associated with important physiological functions in mammals and it is widely distributed in several tissues such as brain, liver, kidney, pancreas, spleen and lungs. There is accumulating evidence for the involvement of DPPIII in oxidative stress, pain, cell cycle regulation, carcinogenesis and inflammation, however the exact role of DPPIII in physiology and disease-related processes remains elusive. To address involment of DPPIII in oxidative stress dppIII-knock-out mouse model were generated as well as mouse embryonic fibroblast cell line (MEF). The presence or lack of DPPIII in generated MEF cells was determined by genotyping and confirmed with fluorometrically measuring of DPPIII activity. The absence of DPPIII increases the hydrogen peroxide (H2O2) concentration but also the relative level of reactive oxygen radicals (ROS) in the MEF cells when compared to the wild type where the levels of H2O2 and ROS are significantly lower. This is supported by the increased concentration of Malondialdehyde one of lipid peroxidation markers. Elevated levels of oxidative stress markers such as lipid peroxidation and ROS generation in cells lacking DPPIII suggest an important role for DPPIII in maintaining homeostasis and his involvement in the oxidative stress defens.