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Oxidative stress in autoimmune rheumatic diseases.
Free Radic Biol Med. 2018 09; 125:3-14.FR

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.

Authors+Show Affiliations

University of Exeter Medical School, St Luke's Campus, Exeter, Devon EX1 2LU, UK.Centre for Biochemical Pharmacology, William Harvey Research Institute, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK.University of Exeter Medical School, St Luke's Campus, Exeter, Devon EX1 2LU, UK.University of Exeter Medical School, St Luke's Campus, Exeter, Devon EX1 2LU, UK.University of Exeter Medical School, St Luke's Campus, Exeter, Devon EX1 2LU, UK; Department of Rheumatology, Princess Elizabeth Orthopaedic Centre, Royal Devon and Exeter NHS Foundation Trust (Wonford), Exeter EX2 5DW, UK.University of Exeter Medical School, St Luke's Campus, Exeter, Devon EX1 2LU, UK. Electronic address: p.g.winyard@exeter.ac.uk.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

29859343

Citation

Smallwood, Miranda J., et al. "Oxidative Stress in Autoimmune Rheumatic Diseases." Free Radical Biology & Medicine, vol. 125, 2018, pp. 3-14.
Smallwood MJ, Nissim A, Knight AR, et al. Oxidative stress in autoimmune rheumatic diseases. Free Radic Biol Med. 2018;125:3-14.
Smallwood, M. J., Nissim, A., Knight, A. R., Whiteman, M., Haigh, R., & Winyard, P. G. (2018). Oxidative stress in autoimmune rheumatic diseases. Free Radical Biology & Medicine, 125, 3-14. https://doi.org/10.1016/j.freeradbiomed.2018.05.086
Smallwood MJ, et al. Oxidative Stress in Autoimmune Rheumatic Diseases. Free Radic Biol Med. 2018;125:3-14. PubMed PMID: 29859343.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidative stress in autoimmune rheumatic diseases. AU - Smallwood,Miranda J, AU - Nissim,Ahuva, AU - Knight,Annie R, AU - Whiteman,Matthew, AU - Haigh,Richard, AU - Winyard,Paul G, Y1 - 2018/05/30/ PY - 2018/02/10/received PY - 2018/05/15/revised PY - 2018/05/28/accepted PY - 2018/6/3/pubmed PY - 2019/9/12/medline PY - 2018/6/3/entrez KW - 3-nitrotyrosine KW - Antioxidant enzyme KW - Autoimmunity KW - Clinical marker KW - Hydrogen peroxide KW - Hydrogen sulfide KW - NADPH oxidase KW - Nitric oxide synthase KW - Nitrite reductase KW - Peroxiredoxin KW - Post-translational modification KW - Reactive nitrogen species KW - Reactive oxygen species KW - Reactive sulfur species KW - Rheumatoid arthritis KW - Scleroderma KW - Sjögren's syndrome KW - Superoxide anion radical KW - Systemic lupus erythematosus KW - Thioredoxin SP - 3 EP - 14 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 125 N2 - 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. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/29859343/Oxidative_stress_in_autoimmune_rheumatic_diseases_ DB - PRIME DP - Unbound Medicine ER -