Oxalate-induced activation of PKC-{alpha} and -{delta} regulates NADPH oxidase-mediated oxidative injury in renal tubular epithelial cells

Oxalate-induced oxidative stress contributes to cell injury and promotes renal deposition of calcium oxalate crystals. However, we do not know how oxalate stimulates reactive oxygen species (ROS) in renal tubular epithelial cells. We investigated the signaling mechanism of oxalate-induced ROS formation in these cells and found that oxalate significantly increased membrane-associated protein kinase C (PKC) activity while at the same time lowering cytosolic PKC activity. Oxalate markedly translocated PKC- and - from the cytosol to the cell membrane. Pretreatment of LLC-PK1 cells with specific inhibitors of PKC- or - significantly blocked oxalate-induced generation of superoxide and hydrogen peroxide along with NADPH oxidase activity, LDH release, lipid hydroperoxide formation, and apoptosis....Click here.