Redox Signaling - Chemical Principles

In the 1980s, the field now called redox biology made two significant turns. Instead of focusing on oxidative damage resulting in pathology, alterations in the balance of oxidants and the ability to remove them introduced the concept of oxidative stress. Even before that, it was known that non-lethal oxidative exposure... read morecould induce antioxidant enzymes and even enhance or mimic physiological receptor-mediated signaling, but the mechanisms remained obscure. In the 1990s, the addition of low concentrations of peroxides to cells was used to identify some of the specific targets, such as the transcription factors AP-1 and NF-B but still the direct targets for the peroxides were obscure. Indeed, this was not helped by use of exogenous peroxide at doses that were several orders of magnitude greater in mass as well as concentration than the all the potential targets in the cells in the plate. Fortunately, the realization of this by those cognizant of rate constants and kinetics led to the use of more physiological models, particularly studies depending on endogenously generated reactive species including superoxide, hydrogen peroxide, lipid hydroperoxides, and nitric oxide. There has also now been a greater focus on using physiological concentrations of oxygen in cell culture. This movement towards redox biology done under conditions approaching physiological will increase the accurate identification of specific targets, mostly proteins with cysteines in critical locations, and a greater understanding of the chemistry of redox signaling that this series will address.