Neutrophil‐mediated oxidation of erythrocyte peroxiredoxin 2 as a potential marker of oxidative stress in inflammation

Abstract

Peroxiredoxin 2 (Prx2) is an abundant thiol protein in erythrocytes. It is oxidized readily on exposure to hydrogen peroxide (H2O2) and provides antioxidant protection by cycling between its reduced and disulfide-bonded forms. To test whether Prx2 oxidation could occur in pathological situations where neutrophils are activated, we exposed human erythrocytes to stimulated neutrophils and measured Prx2 oxidation by immunoblotting of nonreducing gels. With phorbol myristate acetate, lipopolysaccharide or Staphylococcus aureus Prx2 dimer increased from <5% to up to 100% depending on neutrophil number and incubation time. Studies with inhibitors and myeloperoxidase-deficient neutrophils showed that H2O2 generated by the neutrophil NADPH oxidase was responsible. Prx2 oxidation was detected at erythrocyte:neutrophil ratios found in blood and reversed over time as the oxidative burst subsided. Acidotic conditions also increased erythrocyte Prx2 oxidation. In a mouse model of endotoxemia induced by lipopolysaccharide, oxidized Prx2 increased transiently from <1 to 15%, then reverted to baseline by 24 h. No increase was seen in mice lacking NADPH oxidase activity. These results indicate that erythrocyte Prx2 scavenges H2O2 produced during inflammation. Oxidized erythrocyte Prx2 could be a sensitive real-time marker of systemic neutrophil activation and an early indicator of inflammation and oxidative stress.

A simple high performance liquid chromatography method for quantitatively determining the reduced form of peroxiredoxin 2 and the mass spectrometric analysis of its oxidative status

“…It has been reported that the hyperoxidized forms of Prx family proteins can be found in neuronal cells [7], the brains of patients with Alzheimer's disease [8], patients with asthma [9] and patients with sepsis [10]. Additionally, Prx2 has been reported to be aberrantly expressed in several cancer cell lines [11][12][13][14].…”

Evaluation of oxidative stress and antioxidant status: Correlation with the severity of sepsis

“…Similar observations are found when we correlated SOD activity with SOFA (Figure C) and APACHE II (Figure D). Another important antioxidant enzyme CAT which is associated with the H 2 O 2 destruction, thereby, protects the cells and tissues from H 2 O 2 ‐mediated toxicity . Catalase activity's antioxidant action come into the picture when free radicals circulate into the bloodstream via erythrocyte catalase, where it prevents meta‐haemoglobin accumulation and finally degrades H 2 O 2 .…”

Cerebrospinal Fluid Biomarker Candidates Associated with Human WNV Neuroinvasive Disease

“…Peroxiredoxins have been recently reviewed as biomarkers of oxidative stress [65], which is considered one cause of pathogenic mechanisms in neurological diseases. In particular, oxidation of PRDX2 was described to occur in pathological situations and inflammation where neutrophils are activated [66]. PRDX2 has been reported contributing to neuroprotection and was proposed for treatment for neurodegenerative diseases [67].…”