Interplay between physiological/pathophysiological H2O2 generation and the anti-oxidative response mechanism. a H2O2 is produced, e.g. in response to growth factors by the NOX/SOD system and enters cells through simple diffusion and facilitated diffusion through AQPs, respectively, leading to increased intracellular H2O2 levels. b Peroxiredoxins (Prx) act as highly active redox sensors and are part of one of the main H2O2 detoxifying systems. Hyperoxidation inactivates Prxs allowing c the oxidation of sensitive cysteine residues in cellular proteins including transcription factors. d The Nrf2 system is activated in response to increased H2O2 levels leading to the anti-oxidative response. AQP, aquaporin; GF, growth factor; GFR, growth factor receptor.