2-Cys Peroxiredoxins: Emerging Hubs Determining Redox Dependency of Mammalian Signaling Networks

Jinah Park,Sunmi Lee,Sanghyuk Lee,Sang Won Kang

doi:10.1155/2014/715867

Abstract

Mammalian cells have a well-defined set of antioxidant enzymes, which includes superoxide dismutases, catalase, glutathione peroxidases, and peroxiredoxins. Peroxiredoxins are the most recently identified family of antioxidant enzymes that catalyze the reduction reaction of peroxides, such as H2O2. In particular, typical 2-Cys peroxiredoxins are the featured peroxidase enzymes that receive the electrons from NADPH by coupling with thioredoxin and thioredoxin reductase. These enzymes distribute throughout the cellular compartments and, therefore, are thought to be broad-range antioxidant defenders. However, recent evidence demonstrates that typical 2-Cys peroxiredoxins play key signal regulatory roles in the various signaling networks by interacting with or residing near a specific redox-sensitive molecule. These discoveries help reveal the redox signaling landscape in mammalian cells and may further provide a new paradigm of therapeutic approaches based on redox signaling.

Highlights

It is generally accepted that the cellular antioxidant enzymes belong to a group of the oxidoreductase enzymes maintaining the cellular redox homeostasis
The importance of antioxidant enzymes is given a spotlight after a paradigm shift of the cellular function of reactive oxygen species (ROS) from toxic respiratory by-products to a signaling second messenger
Prxs are classified by the number of cysteine residues involved in the peroxidase activity: 2-Cys Prxs and 1-Cys Prx

Summary

Introduction

It is generally accepted that the cellular antioxidant enzymes belong to a group of the oxidoreductase enzymes maintaining the cellular redox homeostasis. Prx was shown to be phosphorylated at Tyr194 by protein tyrosine kinases, such as Lck and Abl, in vitro and in various mammalian cells treated with growth factors [39] This evidence is significant in terms of that the inactivation of Prx by phosphorylation in caveolae membrane microdomain could alter the local redox status. It is clear that the phosphorylation-dependent inactivation takes a physiological advantage of the dynamic regulation linked to the intracellular kinase/phosphatase signaling network compared to Prx inactivation by overoxidation, as the reversal by sulfiredoxin of the latter is a slow reaction requiring an ATP energy demand [40, 41] How does such phosphorylation regulate Prx peroxidase activity?

O2 Trx ASK-1

Signaling Role of 2-Cys Prxs Beyond Peroxidase Enzyme

Conclusion