Several recent studies have reported that reactive oxygen species (ROS), superoxide anion and hydrogen peroxide (H2O2), play important roles in various cellular signaling networks. NADPH oxidase (Nox) isozymes have been shown to mediate receptor-mediated ROS generation for physiological signaling processes involved in cell growth, differentiation, apoptosis, and fibrosis. Detectable intracellular levels of ROS can be induced by the electron leakage from mitochondrial respiratory chain as well as by activation of cytochrome p450, glucose oxidase and xanthine oxidase, leading to oxidative stress. The up-regulation and the hyper-activation of NADPH oxidases (Nox) also likely contribute to oxidative stress in pathophysiologic stages. Elevation of the renal ROS level through hyperglycemia-mediated Nox activation results in the oxidative stress which induces a damage to kidney tissues, causing to diabetic nephropathy (DN). Nox inhibitors are currently being developed as the therapeutics of DN. In this review, we summarize Nox-mediated ROS generation and development of Nox inhibitors for therapeutics of DN treatment.
Bibliographical noteFunding Information:
This work was supported by Aging project (2017M3A9D 8062955 to YSB) and Bio-SPC (2018M3A9G1075771 to YSB) funded by the National Research Foundation of Korea (NRF) and Ministry of Science and ICT.
© 2020 The Korean Society of Applied Pharmacology.
- Diabetic nephropathy
- NADPH oxidase
- Nox inhibitor
- Oxidative stress
- Signal transduction