Work

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

Year: 2025

Type: article

Abstract: The oxidant hydrogen peroxide (H 2 O 2 ) 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 H 2 O 2 decomposition. In the present study, we directly examined the ability of cytoglobin to decompose H 2 O 2 . Carotid arteries from cytoglobin knockout mice were more sensitive to glycolytic inhibition by H 2 O 2 than arteries from wild type mice. In addition, the ectopic expression of cytoglobin in cultured cells limited the inhibitory effect of H 2 O 2 on glycolysis and reversed the oxidative inactivation of the glycolytic enzyme GAPDH. Cytoglobin facilitated the reduction of the thiol-based H 2 O 2 sensor Hyper7 after H 2 O 2 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 H 2 O 2 concentrations indicated that purified cytoglobin consumes H 2 O 2 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 H 2 O 2 . • Cytoglobin expressed in vessels, in fibroblasts and smooth muscle cells. • Consumes intracellular hydrogen peroxide and promotes glycolysis. • In vitro, cytoglobin competes with peroxiredoxin 2. • Reaction with hydrogen peroxide requires heme center and cysteine 83.

Source: Redox Biology

DOI: 10.1016/j.redox.2025.103633