Roles of reactive oxygen species: signaling and regulation of cellular functions.

Reactive oxygen species (ROS) are the side products (H2O2, O2.-, and OH.) of general metabolism and are also produced specifically by the NADPH oxidase system in most cell types. Cells have a very efficient antioxidant defense to counteract the toxic effect of ROS. The physiological significance of ROS is that ROS at low concentrations are able to mediate cellular functions through the same steps of intracellular signaling, which are activated by natural stimuli. Moreover, a variety of natural stimuli act through the intracellular formation of ROS that change the intracellular redox state (oxidation-reduction). Thus, the redox state is a part of intracellular signaling. As such, ROS are now considered signal molecules at nontoxic concentrations. Progress has been achieved in studying the oxidative activation of gene transcription in animal cells and bacteria. Changes in the redox state of intracellular thiols are considered to be an important mechanism that regulates cell functions.