Antioxidants & Redox Signaling

Hydrogen peroxide (H₂O₂) is a well-documented component of living cells. It plays important roles in host defense and oxidative biosynthetic reactions. In addition there is growing evidence that at low levels, H₂O₂ also functions as a signaling agent, particularly in higher organisms. This review evaluates the evidence that H₂O₂ functions as a signaling agent in higher organisms in light of the known biology and biochemistry of H₂O₂. All aerobic organisms studied to date from prokaryotes to humans appear to tightly regulate their intracellular H₂O₂ concentrations at relatively similar levels. Multiple biochemical strategies for rapidly reacting with these low endogenous levels of H₂O₂ have been elucidated from the study of peroxidases and catalases. Welldefined biochemical pathways involved in the response to exogenous H₂O₂ have been described in both prokaryotes and yeast. In animals and plants, regulated enzymatic systems for generating H₂O₂ have been described. In addition oxidation-dependent steps in signal transduction pathways are being uncovered, and evidence is accumulating regarding the nature of the specific reactive oxygen species involved in each of these pathways. Application of physiologic levels of H₂O₂ to mammalian cells has been shown to stimulate biological responses and to activate specific biochemical pathways in these cells.