Oxidative stress in autoimmune rheumatic diseases - PubMed (original) (raw)

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Oxidative stress in autoimmune rheumatic diseases

Miranda J Smallwood et al. Free Radic Biol Med. 2018 Sep.

Abstract

The management of patients with autoimmune rheumatic diseases such as rheumatoid arthritis (RA) remains a significant challenge. Often the rheumatologist is restricted to treating and relieving the symptoms and consequences and not the underlying cause of the disease. Oxidative stress occurs in many autoimmune diseases, along with the excess production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The sources of such reactive species include NADPH oxidases (NOXs), the mitochondrial electron transport chain, nitric oxide synthases, nitrite reductases, and the hydrogen sulfide producing enzymes cystathionine-β synthase and cystathionine-γ lyase. Superoxide undergoes a dismutation reaction to generate hydrogen peroxide which, in the presence of transition metal ions (e.g. ferrous ions), forms the hydroxyl radical. The enzyme myeloperoxidase, present in inflammatory cells, produces hypochlorous acid, and in healthy individuals ROS and RNS production by phagocytic cells is important in microbial killing. Both low molecular weight antioxidant molecules and antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and peroxiredoxin remove ROS. However, when ROS production exceeds the antioxidant protection, oxidative stress occurs. Oxidative post-translational modifications of proteins then occur. Sometimes protein modifications may give rise to neoepitopes that are recognized by the immune system as 'non-self' and result in the formation of autoantibodies. The detection of autoantibodies against specific antigens, might improve both early diagnosis and monitoring of disease activity. Promising diagnostic autoantibodies include anti-carbamylated proteins and anti-oxidized type II collagen antibodies. Some of the most promising future strategies for redox-based therapeutic compounds are the activation of endogenous cellular antioxidant systems (e.g. Nrf2-dependent pathways), inhibition of disease-relevant sources of ROS/RNS (e.g. isoform-specific NOX inhibitors), or perhaps specifically scavenging disease-related ROS/RNS via site-specific antioxidants.

Keywords: 3-nitrotyrosine; Antioxidant enzyme; Autoimmunity; Clinical marker; Hydrogen peroxide; Hydrogen sulfide; NADPH oxidase; Nitric oxide synthase; Nitrite reductase; Peroxiredoxin; Post-translational modification; Reactive nitrogen species; Reactive oxygen species; Reactive sulfur species; Rheumatoid arthritis; Scleroderma; Sjögren's syndrome; Superoxide anion radical; Systemic lupus erythematosus; Thioredoxin.

Copyright © 2018 Elsevier Inc. All rights reserved.

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