We have located links that may give you full text access.
Autophagy protects against redox-active trace metal-induced cell death in rabbit synovial fibroblasts through Toll-like receptor 4 activation.
Experimental Cell Research 2018 November 7
Reactive oxygen species (ROS) are implicated to play a role in initiating rheumatoid arthritis (RA) pathogenesis. We have investigated the mechanism(s) by which essential redox-active trace metals (RATM) may induce cell proliferation and cell death in rabbit synovial fibroblasts. These fibroblast-like synovial (FLS) cells, which express Toll-like receptor 4 (TLR4), were used as a model system that plays a role in potentially initiating RA through oxidative stress. Potassium peroxychromate (PPC, [Cr5+ ]), ferrous chloride (FeCl2 , [Fe2+ ]), and cuprous chloride (CuCl, [Cu+ ]) in the indicated valency states were used as exogenous pro-oxidants that can induce oxidative stress through TLR4 coupled activation that also causes HMGB1 release. We measured the proliferation index (PI) of FLS, and examined the effect of RATM oxidants on apoptosis and autophagy by fluorescence cell-sorting flow cytometry (FC). Cell cycle was analysed by FC and autophagy-related protein expression levels were measured by western blot. Our data showed that as RATM as prooxidants increased intracellular ROS (iROS) that can induce oxidative stress. Whereas iROS increased PI in FLS, these reactive species also protected cells against apoptosis by inducing autophagy. Our results indicate that ROS/TLR4-coupled activation may contribute to the pathogenesis of RA in FLS by induction of autophagy. The signalling pathway by which inflammation and its tissue destructive sequel may occur in RA underlies the need for developing therapeutic agents that can inhibit release of tissue-damaging high mobility group box 1 (HMGB1), cytokines, and possess both trace metal chelating capacity and oxidant scavenging properties in a directed combinatorial therapy for RA.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app