Low survival rate and muscle fiber-dependent aging effects in the McArdle disease mouse model

Real-Martinez, Alberto; Brull, Astrid; Huerta, Jordi; Tarrasó, Guillermo; Lucía, Alejandro; Martín, Miguel; Arenas, Joaquín; Andreu, Antoni L.; Nogales‐Gadea, Gisela; Vissing, John; Krag, Thomas; Luna, Noemí de; Pinós, Tomàs

doi:10.1038/s41598-019-41414-8

Cited by 11 publications

(23 citation statements)

References 29 publications

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“…However, the generated mouse model has some disadvantages, such as much higher glycogen accumulation in muscles than observed in patients, because of faster metabolic rates in mice. Additionally, the mouse McArdle model shows a high level of perinatal and post-weaning mortality [ 75 ]. It was also observed that the glucose metabolism pathways, which were activated to compensate for the lack of PYGM, are different in the mouse model and humans affected by McArdle disease [ 76 , 77 ].…”

Section: Why Use Zebrafish To Study Pygm?mentioning

confidence: 99%

Muscle Glycogen Phosphorylase and Its Functional Partners in Health and Disease

Migocka-Patrzałek

Elías

2021

Cells

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Glycogen phosphorylase (PG) is a key enzyme taking part in the first step of glycogenolysis. Muscle glycogen phosphorylase (PYGM) differs from other PG isoforms in expression pattern and biochemical properties. The main role of PYGM is providing sufficient energy for muscle contraction. However, it is expressed in tissues other than muscle, such as the brain, lymphoid tissues, and blood. PYGM is important not only in glycogen metabolism, but also in such diverse processes as the insulin and glucagon signaling pathway, insulin resistance, necroptosis, immune response, and phototransduction. PYGM is implicated in several pathological states, such as muscle glycogen phosphorylase deficiency (McArdle disease), schizophrenia, and cancer. Here we attempt to analyze the available data regarding the protein partners of PYGM to shed light on its possible interactions and functions. We also underline the potential for zebrafish to become a convenient and applicable model to study PYGM functions, especially because of its unique features that can complement data obtained from other approaches.

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Section: Why Use Zebrafish To Study Pygm?mentioning

confidence: 99%

Muscle Glycogen Phosphorylase and Its Functional Partners in Health and Disease

Migocka-Patrzałek

Elías

2021

Cells

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“…McArdle (PYGM R50X/R50X ) and representative wild-type (PYGM wt/wt ) mice were generated on a C57BL/6 background and extensively characterized as previously described (27,28).…”

Section: Animals and Ethical Approvalmentioning

confidence: 99%

Depletion of ATP Limits Membrane Excitability of Skeletal Muscle by Increasing Both ClC1-Open Probability and Membrane Conductance

et al. 2020

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Activation of skeletal muscle contractions require that action potentials can be excited and propagated along the muscle fibers. Recent studies have revealed that muscle fiber excitability is regulated during repeated firing of action potentials by cellular signaling systems that control the function of ion channel that determine the resting membrane conductance (G m). In fast-twitch muscle, prolonged firing of action potentials triggers a marked increase in G m , reducing muscle fiber excitability and causing action potential failure. Both ClC-1 and K ATP ion channels contribute to this G m rise, but the exact molecular regulation underlying their activation remains unclear. Studies in expression systems have revealed that ClC-1 is able to bind adenosine nucleotides, and that low adenosine nucleotide levels result in ClC-1 activation. In three series of experiments, this study aimed to explore whether ClC-1 is also regulated by adenosine nucleotides in native skeletal muscle fibers, and whether the adenosine nucleotide sensitivity of ClC-1 could explain the rise in G m muscle fibers during prolonged action potential firing. First, whole cell patch clamping of mouse muscle fibers demonstrated that ClC-1 activation shifted in the hyperpolarized direction when clamping pipette solution contained 0 mM ATP compared with 5 mM ATP. Second, three-electrode G m measurement during muscle fiber stimulation showed that glycolysis inhibition, with 2-deoxy-glucose or iodoacetate, resulted in an accelerated and rapid >400% G m rise during short periods of repeated action potential firing in both fast-twitch and slow-twitch rat, and in human muscle fibers. Moreover, ClC-1 inhibition with 9-anthracenecarboxylic acid resulted in either an absence or blunted G m rise during action potential firing in human muscle fibers. Third, G m measurement during repeated action potential firing in muscle fibers from a murine McArdle disease model suggest that the rise in G m was accelerated in a subset of fibers. Together, these results are compatible with ClC-1 function being regulated by the level of adenosine nucleotides in native tissue, and that the channel operates as a sensor of skeletal muscle metabolic state, limiting muscle excitability when energy status is low.

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“…To investigate the effects of SFe on different muscle types, TA muscle was stained with PAS. PAS can differentiate oxidative red (slow twitch) fibers from glycolytic white (fast twitch) fibers according to glycogen content [20–22]. The number of oxidative red fibers did not differ between the 20M and 16M CON groups but was significantly increased in the 20M SFe group compared with the 20M CON group (Figures 3(b) and 3(e)).…”

Section: Resultsmentioning

confidence: 99%

Anti‐Aging Effects of Schisandrae chinensis Fructus Extract: Improvement of Insulin Sensitivity and Muscle Function in Aged Mice

Choi

Seo

Yeon

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Schisandrae chinensis Fructus has a long history of medicinal use as a tonic, a sedative, and an antitussive drug. In this study, we investigated the beneficial effects of Schisandrae chinensis Fructus ethanol extract (SFe) on metabolism in an aged mouse model. Sixteen-month-old C57BL/6J mice were fed with a diet supplemented with SFe for 4 months. Insulin sensitivity was lower at 20 months of age than at 16 months of age; however, the decrease in insulin sensitivity was less in SFe-fed mice. SFe supplementation also appeared to improve glucose tolerance. Body weight gain was lower in SFe-fed mice than in mice fed the control diet. Body fat mass was lower and the lean mass was higher in SFe-fed mice. In addition, the grip strength was enhanced in SFe-fed mice. Histological analysis of the tibialis anterior muscle showed that the size of myofiber and slow-twitch red muscle was increased by SFe supplementation. The expression of proteins related to muscle protein synthesis such as phospho-Erk1 and phospho-S6K1 was increased by SFe supplementation. The mRNA expression of genes related to myogenesis and their encoded proteins such as MyoD, Myf5, MRF4, myogenin, and myosin heavy chain, was increased, whereas that of genes related to muscle degradation, such as atrogin-1, MuRF-1, and myostatin, were decreased relative to control mice. These results suggest that SFe supplementation might have beneficial effects for the improvement of insulin sensitivity and inhibition of muscle loss that occur with aging.

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Low survival rate and muscle fiber-dependent aging effects in the McArdle disease mouse model

Cited by 11 publications

References 29 publications

Muscle Glycogen Phosphorylase and Its Functional Partners in Health and Disease

Muscle Glycogen Phosphorylase and Its Functional Partners in Health and Disease

Depletion of ATP Limits Membrane Excitability of Skeletal Muscle by Increasing Both ClC1-Open Probability and Membrane Conductance

Anti‐Aging Effects of Schisandrae chinensis Fructus Extract: Improvement of Insulin Sensitivity and Muscle Function in Aged Mice

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