Oxidative stress in autoimmune rheumatic diseases.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620738
Title:
Oxidative stress in autoimmune rheumatic diseases.
Authors:
Smallwood, M. J.; Nissim, A.; Knight, A.R.; Whiteman, M.; Haigh, Richard; Winyard, P. G.
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, 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-triggering ROS/RNS via site-specific antioxidants.
Citation:
Oxidative stress in autoimmune rheumatic diseases. 2018 Free Radic. Biol. Med.
Publisher:
Elsevier
Journal:
Free radical biology & medicine
Issue Date:
30-May-2018
URI:
http://hdl.handle.net/11287/620738
DOI:
10.1016/j.freeradbiomed.2018.05.086
PubMed ID:
29859343
Additional Links:
https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(18)30937-7
Type:
Journal Article
Language:
en
ISSN:
1873-4596
Appears in Collections:
Rheumatology; 2018 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorSmallwood, M. J.en
dc.contributor.authorNissim, A.en
dc.contributor.authorKnight, A.R.en
dc.contributor.authorWhiteman, M.en
dc.contributor.authorHaigh, Richarden
dc.contributor.authorWinyard, P. G.en
dc.date.accessioned2018-07-04T13:50:26Z-
dc.date.available2018-07-04T13:50:26Z-
dc.date.issued2018-05-30-
dc.identifier.citationOxidative stress in autoimmune rheumatic diseases. 2018 Free Radic. Biol. Med.en
dc.identifier.issn1873-4596-
dc.identifier.pmid29859343-
dc.identifier.doi10.1016/j.freeradbiomed.2018.05.086-
dc.identifier.urihttp://hdl.handle.net/11287/620738-
dc.description.abstractThe 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, 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-triggering ROS/RNS via site-specific antioxidants.en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttps://linkinghub.elsevier.com/retrieve/pii/S0891-5849(18)30937-7en
dc.rightsArchived with thanks to Free radical biology & medicineen
dc.subjectWessex Classification Subject Headings::Diseases & disorders of systemic, metabolic or environmental origin::Rheumatologyen
dc.titleOxidative stress in autoimmune rheumatic diseases.en
dc.typeJournal Articleen
dc.identifier.journalFree radical biology & medicineen
dc.type.versionIn press (epub ahead of print)en

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