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Review
. 2015 Jun;116(6):884-92.
doi: 10.1002/jcb.25017.

Thiol redox chemistry: role of protein cysteine oxidation and altered redox homeostasis in allergic inflammation and asthma

Sidra Hoffman  1 , James Nolin, David McMillan, Emiel Wouters, Yvonne Janssen-Heininger, Niki Reynaert
Affiliations
Review

Thiol redox chemistry: role of protein cysteine oxidation and altered redox homeostasis in allergic inflammation and asthma

Sidra Hoffman et al. J Cell Biochem. 2015 Jun.

Abstract

Asthma is a pulmonary disorder, with an estimated 300 million people affected worldwide. While it is thought that endogenous reactive oxygen species (ROS) and reactive nitrogen species (RNS) such as hydrogen peroxide and nitric oxide, are important mediators of natural physiological processes, inflammatory cells recruited to the asthmatic airways have an exceptional capacity for producing a variety of highly reactive ROS and RNS believed to contribute to tissue damage and chronic airways inflammation. Antioxidant defense systems form a tightly regulated network that maintains the redox environment of the intra- as well as extracellular environment. Evidence for an oxidant-antioxidant imbalance in asthmatic airways is demonstrated in a number of studies, revealing decreased total antioxidant capacity as well as lower levels of individual antioxidants. Thiols in the form of GSH and sulfhydryl groups of proteins are among the most susceptible oxidant-sensitive targets, and hence, studies investigating protein thiol redox modifications in biology and disease have emerged. This perspective offers an overview of the combined efforts aimed at the elucidation of mechanisms whereby cysteine oxidations contribute to chronic inflammation and asthma, as well as insights into potential cysteine thiol-based therapeutic strategies.

Keywords: asthma; cysteine; oxidation.

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Figures

Figure 1
Figure 1
Overview of allergen-initiated innate and adaptive immune responses and associated changes in protein thiol redox status. (1) Inhalation of allergens leads to disruption of epithelial cell homeostasis and impaired barrier function, allowing the allergen to interact with dendritic cells and other immune cells, including T cells. (2) Allergens are engulfed and processed by dendritic cells, which present antigenic epitopes to naïve T cells. (3) Naïve T cells polarize leading to recruitment of neutrophils and eosinophils (innate immune response) and activation of B cells, driving the adaptive immune response. (4) Reactive oxygen and nitrogen species are produced by inflammatory cells and structural cells including epithelial cells, resulting in oxidative modifications of reactive cysteines within proteins (P) (5). The downstream effects of oxidant overproduction have traditionally been associated with tissue damage (6). However, altered protein thiol redox biology (7) has emerged as a putative mechanism where oxidants contribute to the chronic features of asthma. This (patho) biological role of oxidants has the potential to be exploited towards the development of new and targeted therapeutics for patients with asthma. H2O2, hydrogen peroxide; O2·−, superoxide; S·, thiyl; NO· nitric oxide; ONOO− peroxynitrite; P-SH, protein thiol; P-SOH, protein sulfenic acid; P-SNO, S-nitrosylation; P-SSG, S-glutathionylation; Grx, glutaredoxin; Srx, sulfiredoxin; Trx, thioredoxin; GSTP, glutathione S-transferase pi; GSSG, glutathione disulfide.
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