Peroxiredoxins as biomarkers of oxidative stress

doi:10.1016/j.bbagen.2013.08.001

Biochimica et Biophysica Acta (BBA) - General Subjects

Volume 1840, Issue 2, February 2014, Pages 906-912

https://doi.org/10.1016/j.bbagen.2013.08.001 Get rights and content

Highlights

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Peroxiredoxins are endogenous antioxidants and redox sensors.
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Various biochemical properties of the peroxiredoxins make them suitable as markers of oxidative stress.
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Different methods are available to detect peroxiredoxin oxidation.
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Oxidized peroxiredoxins have been detected in experimental and clinical samples.

Abstract

Background

Peroxiredoxins (Prxs) are a class of abundant thiol peroxidases that degrade hydroperoxides to water. Prxs are sensitive to oxidation, and it is hypothesized that they also act as redox sensors. The accumulation of oxidized Prxs may indicate disruption of cellular redox homeostasis.

Scope of review

This review discusses the biochemical properties of the Prxs that make them suitable as endogenous biomarkers of oxidative stress, and describes the methodology available for measuring Prx oxidation in biological systems.

Major conclusions

Two Prx oxidation products accumulate in cells under increased oxidative stress: an intermolecular disulfide and a hyperoxidized form. Methodologies are available for measuring both of these redox states, and oxidation has been reported in cells and tissues under oxidative stress from external or internal sources.

General significance

Monitoring the oxidation state of Prxs provides insight into disturbances of cellular redox homeostasis, and complements the use of exogenous probes of oxidative stress. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.

Introduction

Peroxiredoxins (Prxs) are a class of thiol peroxidases that degrade hydroperoxides to water [1], [2]. Catalase and glutathione peroxidases also remove hydroperoxides, and these enzymes were considered to be the major enzymes responsible for protecting cells against hydroperoxides. However, recent data on the reactivity and abundance of the Prxs has revealed them to also be prominent members of the antioxidant defence network. There are indications that the role of Prxs in antioxidant defence is more complex than the removal of hydroperoxides. Prxs can be easily inactivated by hydrogen peroxide, disabling peroxidase activity and thereby limiting their ability to act as antioxidants [3]. Eukaryote Prxs are considerably more susceptible to oxidative inactivation than prokaryote family members, suggesting a gain-of-function that has been selected by evolution [4]. Prxs have complex oligomeric structures that are influenced by the redox state of the protein [5], [6], [7]. This combined knowledge has led to the hypothesis that Prxs act as redox sensors, regulating signal transduction pathways upon oxidation [8], [9].

Redox sensors detect disturbances in redox homeostasis, and as such, they are ideal entities to monitor for signs of oxidative stress. Many redox signalling models invoke transient and localized generation of reactive oxygen species. Markers of global protein and lipid oxidation associated with oxidative damage are insufficiently sensitive for detecting subtle modulations of redox homeostasis. To aid this endeavour, an array of redox reporter probes has become available for experimental use. An alternate approach is to specifically monitor endogenous redox-sensitive proteins. This review discusses the biochemical properties of the Prxs that make them suitable as sensitive biomarkers of oxidative stress, describes current methodology for measuring Prx oxidation in biological samples, and highlights studies where oxidation has been reported.

Section snippets

Biochemical properties of the Prxs

Prxs are highly conserved proteins that have been identified in all phyla. Many species contain more than one Prx; mammals have six different Prxs, with Prxs 1, 2 and 6 located in the cytosol, Prx 3 in the mitochondrial matrix, Prx 4 in the endoplasmic reticulum and Prx 5 in mitochondria, peroxisomes and the cytosol. Prx activity is characterised by a peroxidatic cysteine that is oxidized to a sulfenic acid by hydroperoxides including hydrogen peroxide, organic peroxides, peptide and protein

Prxs as markers of oxidative stress

The oxidized dimer of the typical 2-Cys Prxs accumulates during the breakdown of hydroperoxides, both because the rate of oxidation is faster than the rate of reduction and that Prxs are present at higher concentrations in cells than the major reductant thioredoxin. The extent of the bottleneck will vary depending on cell type and metabolic status, but monitoring the redox status of the 2-Cys Prxs could reveal subtle alterations in the rate of hydroperoxide generation, or impairment of the

Summary

Several features of the Prxs make measurement of their redox state a valuable biomarker of oxidative stress. They are abundant and highly reactive proteins, and oxidation has been observed where few if any other redox modifications are detectable. This enables detection of more subtle disturbances in redox homeostasis that could occur during signalling events, although sensitivity will vary between cell types depending on the robustness of their reduction systems. The varied intracellular

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^☆: This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.

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ReviewPeroxiredoxins as biomarkers of oxidative stress☆

Highlights

Abstract

Background

Scope of review

Major conclusions

General significance

Introduction

Section snippets

Biochemical properties of the Prxs

Prxs as markers of oxidative stress

Summary

Trends Biochem. Sci.

J. Biol. Chem.

FEBS Lett.

Free Radic. Biol. Med.

J. Biol. Chem.

J. Biol. Chem.

Free Radic. Biol. Med.

J. Mol. Biol.

J. Biol. Chem.

Structure

J. Biol. Chem.

J. Biol. Chem.

FEBS Lett.

J. Biol. Chem.

Cell

J. Biol. Chem.

J. Biol. Chem.

Free Radic. Biol. Med.

Free Radic. Biol. Med.

Methods Enzymol.

FEBS Lett.

Free Radic. Biol. Med.

Blood

Free Radic. Biol. Med.

Free Radic. Biol. Med.

Biochem. Pharmacol.

FEBS Lett.

Toxicology

Toxicology

Free Radic. Biol. Med.

Free Radic. Biol. Med.

J. Biol. Chem.

Biochim. Biophys. Acta

Review
Peroxiredoxins as biomarkers of oxidative stress☆