Oxidative Modification of Proteins: An Emerging Mechanism of Cell Signaling

Aimee Landar,Anne R Diers,Stephanie B Wall,Joo-Yeun Oh

doi:10.3389/fphys.2012.00369

Abstract

There are a wide variety of reactive species which can affect cell function, including reactive oxygen, nitrogen, and lipid species. Some are formed endogenously through enzymatic or non-enzymatic pathways, and others are introduced through diet or environmental exposure. Many of these reactive species can interact with biomolecules and can result in oxidative post-translational modification of proteins. It is well documented that some oxidative modifications cause macromolecular damage and cell death. However, a growing body of evidence suggests that certain classes of reactive species initiate cell signaling by reacting with specific side chains of peptide residues without causing cell death. This process is generally termed “redox signaling,” and its role in physiological and pathological processes is a subject of active investigation. This review will give an overview of oxidative protein modification as a mechanism of redox signaling, including types of reactive species and how they modify proteins, examples of modified proteins, and a discussion about the current concepts in this area.

Highlights

There are a wide variety of reactive species which can affect cell function, including reactive oxygen, nitrogen, and lipid species
We have previously shown that an electrophilic lipid with low reactivity at sublethal doses forms adducts with primarily cysteine residues and alters cell signaling (Levonen et al, 2004; Diers et al, 2010a)
Our studies have shown that 15d-PGJ2 reacts with a small group of proteins at low levels, and that with increasing exposure, the number of modified proteins and extent of modification increases (Oh et al, 2008)

Summary

Introduction

There are a wide variety of reactive species which can affect cell function, including reactive oxygen, nitrogen, and lipid species. Some are formed endogenously through enzymatic or non-enzymatic pathways, and others are introduced through diet or environmental exposure Many of these reactive species can interact with biomolecules and can result in oxidative post-translational modification of proteins. Dietary compounds such as curcumin in curry, and sulforaphane in cruciferous vegetables (e.g., brussel sprouts) are electrophilic and reactive with protein thiols (Brennan and O’Neill, 1998; Hong et al, 2005). These compounds have been shown to have potent anti-inflammatory properties and potential health benefits (Clarke et al, 2008; Lopez-Lazaro, 2008; Zhao et al, 2011). Other enzymatic sources of reactive species include xanthine oxidase and www.frontiersin.org

Findings

Discussion

Conclusion