Levels of inflammation and oxidative stress, and a role for taurine in dystropathology of the Golden Retriever Muscular Dystrophy dog model for Duchenne Muscular Dystrophy

Terrill, Jessica R.; Duong, Marisa N.; Turner, Rufus; Guiner, Caroline Le; Boyatzis, Amber E.; Grounds, Miranda D.; Arthur, Peter G.

doi:10.1016/j.redox.2016.08.016

Cited by 43 publications

(54 citation statements)

References 106 publications

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“…4). Consistent with this, levels of the classic markers for neutrophils, MPO and neutrophil elastase, closely correspond with elevated protein carbonylation, chlorotyrosine formation and thiol oxidation markers in dystrophic skeletal muscles of mdx mice and GRMD dogs (Terrill et al, 2016a). We have also shown that reversible protein thiol oxidation is especially localised in foci of myonecrosis (Iwasaki et al, 2013), and occurs on muscle proteins such as myosin heavy chain, myosin light chain and tropomyosin, as well as on the glycolytic proteins phosphoglycerate mutase and triosephosphate isomerase (Armstrong et al, 2011;El-Shafey et al, 2011;Iwasaki et al, 2013;Radley-Crabb et al, 2012;Terrill et al, 2012Terrill et al, , 2013aTerrill et al, ,b, 2016a.…”

Section: Reversible Oxidation Of Protein Thiolssupporting

confidence: 70%

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Biomarkers for Duchenne muscular dystrophy: myonecrosis, inflammation and oxidative stress

Grounds

Terrill

Al-Mshhdani

et al. 2020

Disease Models &Amp; Mechanisms

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Duchenne muscular dystrophy (DMD) is a lethal, X-linked disease that causes severe loss of muscle mass and function in young children. Promising therapies for DMD are being developed, but the long lead times required when using clinical outcome measures are hindering progress. This progress would be facilitated by robust molecular biomarkers in biofluids, such as blood and urine, which could be used to monitor disease progression and severity, as well as to determine optimal drug dosing before a full clinical trial. Many candidate DMD biomarkers have been identified, but there have been few follow-up studies to validate them. This Review describes the promising biomarkers for dystrophic muscle that have been identified in muscle, mainly using animal models. We strongly focus on myonecrosis and the associated inflammation and oxidative stress in DMD muscle, as the lack of dystrophin causes repeated bouts of myonecrosis, which are the key events that initiate the resultant severe dystropathology. We discuss the early events of intrinsic myonecrosis, along with early regeneration in the context of histological and other measures that are used to quantify its incidence. Molecular biomarkers linked to the closely associated events of inflammation and oxidative damage are discussed, with a focus on research related to protein thiol oxidation and to neutrophils. We summarise data linked to myonecrosis in muscle, blood and urine of dystrophic animal species, and discuss the challenge of translating such biomarkers to the clinic for DMD patients, especially to enhance the success of clinical trials.

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Section: Reversible Oxidation Of Protein Thiolssupporting

confidence: 70%

“…with mass spectrometry or by immunoblotting using an antibody that can detect halogenated tyrosine (Kato et al, 2005;Winterbourn, 2002). We have shown an increase in tyrosine halogenation in GRMD muscle (Terrill et al, 2016a).…”

Section: Irreversible Oxidative Damage Of Macromoleculesmentioning

confidence: 88%

Biomarkers for Duchenne muscular dystrophy: myonecrosis, inflammation and oxidative stress

Grounds

Terrill

Al-Mshhdani

et al. 2020

Disease Models &Amp; Mechanisms

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“…In patients with DMD and mdx mice, muscle degeneration results from several pathogenic processes, and oxidative stress, fibrosis, and chronic inflammation have major effects on the functional impairment of muscle and on disease progression. 35,36 Our study reveals for the first time that the treatment of mdx mice with catalpol reduces fibrosis and inflammation, major pathogenic pathways that mediate muscle degeneration and functional impairment in DMD. These pathological changes translated into improved skeletal muscle function, as reflected in grip strength in vivo and specific force production and recovery in vitro.…”

Section: Discussionmentioning

confidence: 83%

A potential therapeutic effect of catalpol in Duchenne muscular dystrophy revealed by binding with TAK1

Zhao

Jiang

et al. 2020

J cachexia sarcopenia muscle

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Background Duchenne muscular dystrophy (DMD) is a progressive muscle disease caused by the loss of dystrophin, which results in inflammation, fibrosis, and the inhibition of myoblast differentiation in skeletal muscle. Catalpol, an iridoid glycoside, improves skeletal muscle function by enhancing myogenesis; it has potential to treat DMD. We demonstrate the positive effects of catalpol in dystrophic skeletal muscle. Methods mdx (loss of dystrophin) mice (n = 18 per group) were treated with catalpol (200 mg/kg) for six consecutive weeks. Serum analysis, skeletal muscle performance and histology, muscle contractile function, and gene and protein expression were performed. Molecular docking and ligand-target interactions, RNA interference, immunofluorescence, and plasmids transfection were utilized to explore the protective mechanism in DMD by which catalpol binding with transforming growth factor-βactivated kinase 1 (TAK1) in skeletal muscle. Results Six weeks of catalpol treatment improved whole-body muscle health in mdx mice, which was characterized by reduced plasma creatine kinase (n = 18, À35.1%, P < 0.05) and lactic dehydrogenase (n = 18, À10.3%, P < 0.05) activity. These effects were accompanied by enhanced grip strength (n = 18, +25.4%, P < 0.05) and reduced fibrosis (n = 18, À29.0% for hydroxyproline content, P < 0.05). Moreover, catalpol treatment protected against muscle fatigue and promoted muscle recovery in the tibialis anterior (TA) and diaphragm (DIA) muscles (n = 6, +69.8%, P < 0.05 and + 74.8%, P < 0.001, respectively), which was accompanied by enhanced differentiation in primary myoblasts from DMD patients (n = 6, male, mean age: 4.7 ± 1.9 years) and mdx mice. In addition, catalpol eliminated p-TAK1 overexpression in mdx mice (n = 12, À21.3%, P < 0.05) and primary myoblasts. The catalpol-induced reduction in fibrosis and increased myoblast differentiation resulted from the inhibition of TAK1 phosphorylation, leading to reduced myoblast trans-differentiation into myofibroblasts. Catalpol inhibited the phosphorylation of TAK1 by binding to TAK1, possibly at Asp-206, Thr-208, Asn-211, Glu-297, Lys-294, and Tyr-293. Conclusions Our findings show that catalpol and TAK1 inhibitors substantially improve whole-body muscle health and the function of dystrophic skeletal muscles and may provide a novel therapy for DMD.

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“…Dystrophic patients and mdx mice showed high levels of reactive oxygen species (ROS) and lipid peroxidation [ 5 , 14 ]. Our research group and other researchers have already demonstrated the beneficial effect of antioxidant treatment, such as N-acetylcysteine, ascorbic acid, green tea and taurine, in dystrophic muscles [ 8 , 15 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

Dystrophic phenotype improvement in the diaphragm muscle of mdx mice by diacerhein

et al. 2017

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Chronic inflammation and oxidative stress are striking features of Duchenne muscular dystrophy disease. Diacerhein is an anthraquinone, which exhibits anti-inflammatory and antioxidant properties. Based on their actions, the present study evaluated the effects of diacerhein against myonecrosis, oxidative stress and inflammatory response in the diaphragm muscle of mdx mice and compared these results to current treatment widely used in DMD patients, with a main focus on the impact of prednisone. The results demonstrated that diacerhein treatment prevented muscle damage indicated by a decrease in the IgG uptake by muscle fibers, lower CK levels in serum, reduction of fibers with central nuclei with a concomitant increase in fibers with peripheral nuclei. It also had an effect on the inflammatory process, decreasing the inflammatory area, macrophage staining and TNF-α and IL-1β content. Regarding oxidative stress, diacerhein treatment was effective in reducing the ROS and lipid peroxidation in the diaphragm muscle from mdx mice. Compared to prednisone treatment, our findings demonstrated that diacerhein treatment improved the dystrophic phenotype in the diaphragm muscle of mdx mice similar to that of glucocorticoid therapy. In this respect, this work suggests that diacerhein has a potential use as an alternative drug in dystrophinopathy treatment and recommends that its anti-inflammatory and antioxidants properties in the dystrophic muscle should be better understood.

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Levels of inflammation and oxidative stress, and a role for taurine in dystropathology of the Golden Retriever Muscular Dystrophy dog model for Duchenne Muscular Dystrophy

Cited by 43 publications

References 106 publications

Biomarkers for Duchenne muscular dystrophy: myonecrosis, inflammation and oxidative stress

Biomarkers for Duchenne muscular dystrophy: myonecrosis, inflammation and oxidative stress

A potential therapeutic effect of catalpol in Duchenne muscular dystrophy revealed by binding with TAK1

Dystrophic phenotype improvement in the diaphragm muscle of mdx mice by diacerhein

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