Figure 1.

H₂O₂ signaling in mammalian cells. The binding of growth factors (e.g., EGF or PDGF) to their receptors triggers several downstream events. NADPH oxidase (NOX) is a membrane-bound enzyme complex that can produce superoxide anion (O₂^•−). Activation of this complex (e.g., NOX-2) occurs after the sequential activation of phosphatidylinositol-3-kinase (PI3K) and Rac small GTPase 1 (RAC1) proteins. O₂^•− produced from NOX complex can dismutate to H₂O₂ by superoxide dismutase-3 (SOD3). H₂O₂ can cross the cellular membrane through aquaporin water channels (AQPs) and activates ROS signaling with oxidative modification of critical redox-sensitive Cys in signaling proteins. The targets of H₂O₂ include transcriptional factors (TFs), mitogen-activated protein kinases (MAPKs) and protein Tyr phosphatases (PTPs). Cellular antioxidant systems, such as catalase (CAT), glutathione peroxidases (GPXs) and peroxiredoxins (PRXs) cooperate to maintain redox homeostasis [9,10].