ArticleAnnals of the rheumatic diseases2015
Nitrosative modifications of the Ca2+ release complex and actin underlie arthritis-induced muscle weakness.
Article in Annals of the rheumatic diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03324152 (Effects of High-intensity Interval Training), which is not on this map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effects of High-intensity Interval Training (HIIT) Compared to Low-intensity Exercise in Patients With Recent Onset Polymyositis and Dermatomyositis - a Randomized Controlled Trial
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Sarcopenia and cardiovascular diseases: A systematic review and meta-analysis.Journal of cachexia, sarcopenia and muscle · 2023Pooled it
- Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise.Proceedings of the National Academy of Sciences of the United States of America · 2015Trial
- Methodology Development for Investigating Pathophysiological [Biomedicines · 2025Article
- Downregulated MYL1 Emerges as a Promising Diagnostic Biomarker for Rheumatoid Arthritis.Journal of inflammation research · 2025Article
- Stable oxidative posttranslational modifications alter the gating properties of RyR1.The Journal of general physiology · 2024Article
- From amino-acid to disease: the effects of oxidation on actin-myosin interactions in muscle.Journal of muscle research and cell motility · 2023Review
- Sphingomyelinase activity promotes atrophy and attenuates force in human muscle fibres and is elevated in heart failure patients.Journal of cachexia, sarcopenia and muscle · 2022Article
- Fast skeletal muscle troponin activator CK-2066260 mitigates skeletal muscle weakness independently of the underlying cause.Journal of cachexia, sarcopenia and muscle · 2020Article
- Skeletal muscle redox signaling in rheumatoid arthritis.Clinical science (London, England : 1979) · 2020Review
- Intramuscular mechanisms of overtraining.Redox biology · 2020Review
- Nitrosative Stress and Its Association with Cardiometabolic Disorders.Molecules (Basel, Switzerland) · 2020Review
- A Mechanism for Statin-Induced Susceptibility to Myopathy.JACC. Basic to translational science · 2019Article
- Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis.JCI insight · 2019Article
- The effects of fatigue and oxidation on contractile function of intact muscle fibers and myofibrils isolated from the mouse diaphragm.Scientific reports · 2019Article
- Redox Status and Muscle Pathology in Rheumatoid Arthritis: Insights from Various Rat Hindlimb Muscles.Oxidative medicine and cellular longevity · 2019Article
- Temporomandibular Disorders and Oral Features in Early Rheumatoid Arthritis Patients: An Observational Study.International journal of medical sciences · 2019Observational
- Role of defective CaJournal of cell communication and signaling · 2018Review
- Perceived Versus Performance Fatigability in Patients With Rheumatoid Arthritis.Frontiers in physiology · 2018Review
- Very Low Volume High-Intensity Interval Exercise Is More Effective in Young Than Old Women.BioMed research international · 2018Article
- Muscle Weakness in Rheumatoid Arthritis: The Role of CaEBioMedicine · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
objectiveSkeletal muscle weakness is a prominent clinical feature in patients with rheumatoid arthritis (RA), but the underlying mechanism(s) is unknown. Here we investigate the mechanisms behind arthritis-induced skeletal muscle weakness with special focus on the role of nitrosative stress on intracellular Ca(2+) handling and specific force production.
methodsNitric oxide synthase (NOS) expression, degree of nitrosative stress and composition of the major intracellular Ca(2+) release channel (ryanodine receptor 1, RyR1) complex were measured in muscle. Changes in cytosolic free Ca(2+) concentration ([Ca(2+)]i) and force production were assessed in single-muscle fibres and isolated myofibrils using atomic force cantilevers.
resultsThe total neuronal NOS (nNOS) levels were increased in muscles both from collagen-induced arthritis (CIA) mice and patients with RA. The nNOS associated with RyR1 was increased and accompanied by increased [Ca(2+)]i during contractions of muscles from CIA mice. A marker of peroxynitrite-derived nitrosative stress (3-nitrotyrosine, 3-NT) was increased on the RyR1 complex and on actin of muscles from CIA mice. Despite increased [Ca(2+)]i, individual CIA muscle fibres were weaker than in healthy controls, that is, force per cross-sectional area was decreased. Furthermore, force and kinetics were impaired in CIA myofibrils, hence actin and myosin showed decreased ability to interact, which could be a result of increased 3-NT content on actin.
conclusionsArthritis-induced muscle weakness is linked to nitrosative modifications of the RyR1 protein complex and actin, which are driven by increased nNOS associated with RyR1 and progressively increasing Ca(2+) activation.
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Registered trials
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