Cytoglobin scavenges intracellular hydrogen peroxide and regulates redox signals in the vasculature

The oxidant hydrogen peroxide (H₂O₂) serves as a signaling molecule that alters many aspects of cardiovascular functions and contributes to cardiovascular diseases. Recent studies suggest that cytoglobin - a member of the globin family - may promote electron transfer reactions with proposed functions in H₂O₂ decomposition. In the present study, we directly examined the ability of cytoglobin to decompose H₂O₂. Carotid arteries from cytoglobin knockout mice were more sensitive to glycolytic inhibition by H₂O₂ than arteries from wild type mice. In addition, the ectopic expression of cytoglobin in cultured cells limited the inhibitory effect of H₂O₂ on glycolysis and reversed the oxidative inactivation of the glycolytic enzyme GAPDH. Cytoglobin facilitated the reduction of the thiol-based H₂O₂ sensor Hyper7 after H₂O₂ challenge. The specific substitution of one of two cysteine residues on cytoglobin (C83) inhibited its antioxidant activity, as did the substitutions at the proximal and distal histidine residues. In vitro, direct measurements of H₂O₂ concentrations indicated that purified cytoglobin consumes H₂O₂ at rates comparable to that of peroxiredoxin 2 and that it competitively inhibits the hyperoxidation of peroxiredoxin 2. We propose that cytoglobin may serve as a regulator of intracellular redox signals initiated by H₂O₂.