Nox-4 deletion reduces oxidative stress and injury by PKC-α-associated mechanisms in diabetic nephropathy.
Vicki Thallas-Bonke, Jay C Jha, Stephen P Gray, David Barit, Hermann Haller, Harald HHW Schmidt, Melinda T Coughlan, Mark E Cooper, Josephine M Forbes, Karin AM Jandeleit-Dahm
Physiological Reports | Published : 2014
Current treatments for diabetic nephropathy (DN) only result in slowing its progression, thus highlighting a need to identify novel targets. Increased production of reactive oxygen species (ROS) is considered a key downstream pathway of end-organ injury with increasing data implicating both mitochondrial and cytosolic sources of ROS. The enzyme, NADPH oxidase, generates ROS in the kidney and has been implicated in the activation of protein kinase C (PKC), in the pathogenesis of DN, but the link between PKC and Nox-derived ROS has not been evaluated in detail in vivo. In this study, global deletion of a NADPH-oxidase isoform, Nox4, was examined in mice with streptozotocin-induced diabetes (C5..View full abstract