Calpain/calpastatin activities and substrate depletion patterns during hindlimb unweighting and reweighting in skeletal muscle

Enns, Deborah L.; Raastad, Truls; Ugelstad, Ingrid; Belcastro, A. N.

doi:10.1007/s00421-007-0445-4

Cited by 67 publications

(44 citation statements)

References 56 publications

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“…Although calpains have limited capability to fully degrade complex intramuscular substrates (19), calpain enzymatic activity is upregulated in response to proteolytic stressors, including endurance exercise, muscular dystrophy, and disuse (17,20). The mechanism by which calpains contribute to muscle proteolysis is likely by cleaving myofibrillar proteins into smaller actomyosin fragments (21).…”

Section: Intramuscular Regulation Of Skeletal Muscle Proteolysismentioning

confidence: 99%

Assessment of skeletal muscle proteolysis and the regulatory response to nutrition and exercise

Pasiakos

Carbone

2014

IUBMB Life

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Skeletal muscle proteolysis is highly regulated, involving complex intramuscular proteolytic systems that recognize and degrade muscle proteins, and recycle free amino acid precursors for protein synthesis and energy production. Autophagylysosomal, calpain, and caspase systems are contributors to muscle proteolysis, although the ubiquitin proteasome system (UPS) is the primary mechanism by which actomyosin fragments are degraded in healthy muscle. The UPS is sensitive to mechanical force and nutritional deprivation, as recent reports have demonstrated increased proteolytic gene expression and activity of the UPS in response to resistance and endurance exercise, and short-term negative energy balance. However, consuming dietary protein alone (or free amino acids), or as a primary component of a mixed meal, may attenuate intramuscular protein loss by down-regulating proteolytic gene expression and the catabolic activity of the UPS. Although these studies provide novel insight regarding the intramuscular regulation of skeletal muscle mass, the role of proteolysis in the regulation of skeletal muscle protein turnover in healthy human muscle is not well described. This article provides a contemporary review of the intramuscular regulation of skeletal muscle proteolysis in healthy muscle, methodological approaches to assess proteolysis, and highlights the effects of nutrition and exercise on skeletal muscle proteolysis.

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Section: Intramuscular Regulation Of Skeletal Muscle Proteolysismentioning

confidence: 99%

Assessment of skeletal muscle proteolysis and the regulatory response to nutrition and exercise

Pasiakos

Carbone

2014

IUBMB Life

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“…In contrast to aestivators and hibernators, enzyme activity levels of calpain 1 and 2 have been shown to be increased during hindlimb suspension in rodents (Enns et al, 2007;Taillandier et al, 1996;Yang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Calpain activation in skeletal muscle appears to occur early during hindlimb suspension and can show a progressive increase in activity over time (Enns et al, 2007;Ma et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Evidence that calpains 1 and 2 are important contributors to skeletal muscle disuse atrophy is largely based on examinations of gene expression, protein abundance or enzyme activity (Enns et al, 2007;Haddad et al, 2003;Min et al, 2011;Taillandier et al, 1996).…”

Section: H2omentioning

confidence: 99%

“…Other studies have indicated that calpain activation might be an early, necessary stage in the development of disuse-induced muscle atrophy, but results have been mixed and controversial (Bartoli and Richard, 2005;Enns et al, 2007;Jones et al, 2004;Maes et al, 2007;Taillandier et al, 1996). However, experiments have also demonstrated that pharmacological inhibition of calpain results in prevention of skeletal muscle atrophy imposed by both hindlimb casting and hindlimb suspension (Talbert et al, 2013a;Tischler et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms underlying inhibition of muscle disuse atrophy during aestivation in the green-striped burrowing frog, Cyclorana alboguttata

Reilly¹

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In most mammals, extended inactivity or immobilisation of skeletal muscle (e.g. bedrest, limb-casting or hindlimb unloading) results in muscle disuse atrophy, a process which is characterised by the loss of skeletal muscle mass and function. In stark contrast, animals that experience natural bouts of prolonged muscle inactivity, such as hibernating mammals and aestivating frogs, consistently exhibit limited or no change in either skeletal muscle size or contractile performance. While many of the factors regulating skeletal muscle mass are known, little information exists as to what mechanisms protect against muscle atrophy in some species.Green-striped burrowing frogs (Cyclorana alboguttata) survive in arid environments by burrowing underground and entering into a deep, prolonged metabolic depression known as aestivation. Throughout aestivation, C. alboguttata is immobilised within a cast-like cocoon of shed skin and ceases feeding and moving. Remarkably, these frogs exhibit very little muscle atrophy despite extended disuse and fasting. The overall aim of the current research study was to gain a better understanding of the physiological, cellular and molecular basis underlying resistance to muscle disuse atrophy in C. alboguttata.The first aim of this study was to develop a genomic resource for C. alboguttata by sequencing and functionally characterising its skeletal muscle transcriptome, and to conduct gene expression profiling to identify transcriptional pathways associated with metabolic depression and maintenance of muscle function in aestivating burrowing frogs. A transcriptome was assembled using next-generation short read sequencing followed by a comparison of gene expression patterns between active and four-month aestivating C.alboguttata. This identified a complex suite of gene expression changes that occur in muscle during aestivation and provides evidence that aestivation in burrowing frogs involves transcriptional regulation of genes associated with cytoskeletal remodelling, avoidance of oxidative stress, energy metabolism, the cell stress response, cell death and survival and epigenetic modification. In particular, the expression levels of genes encoding cell cycle regulatory-, pro-survival and chromatin remodelling proteins, such as serine/threonine-protein kinase Chk1, cell division protein kinase 2, survivin, vesicular overexpressed in cancer prosurvival protein 1 and histone-binding protein RBBP4, were upregulated in aestivators.The second aim of this study was to examine the potential role of mitochondrial ROS in the regulation of muscle mass and function during aestivation in C. alboguttata. In III mammals, muscle disuse atrophy has been associated with oxidative damage due to increased mitochondrial ROS production. C. alboguttata reduced skeletal muscle mitochondrial respiration by approximately 50% following four months of aestivation, while mitochondrial ROS production was more than 80% lower in aestivating skeletal muscle relative to controls when mitochondrial substrates were pre...

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Activity, abundance and expression of Ca2+-activated proteases in skeletal muscle of the aestivating frog, Cyclorana alboguttata

2014

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In most mammals, prolonged muscle disuse (e.g. bed-rest, limb casting or spaceflight) results in atrophy of muscle fibres which is largely due to unregulated proteolysis. Although numerous proteolytic pathways are known to participate in muscle disuse atrophy, recent evidence suggests that activation of Ca²⁺-dependent cysteine proteases (calpains) is required for disuse atrophy in limb skeletal muscles. In contrast to typical models of muscle disuse (humans and rodents), animals that experience natural bouts of chronic muscle inactivity, such as hibernating mammals and aestivating frogs, consistently exhibit limited or no change in skeletal muscle size. In the current study, we examined enzyme activity, protein abundance and gene expression levels of calpain isoforms in gastrocnemius muscle of the aestivating frog, Cyclorana alboguttata. We predicted that in aestivating C. alboguttata there would be a downregulation of the abundance, activity and gene expression of calpain 1 and calpain 2. In contrast to our hypothesis, there was no significant decrease in the enzyme activity levels or the relative protein abundances of calpain 1 and calpain 2. Similarly, gene expression assays (both qRT-PCR and RNA Seq data) indicated that calpains were unaffected by aestivation. Western blotting of 'muscle-specific' calpain 3, which is consistently downregulated during atrophic conditions, indicated that this isoform is present in C. alboguttata muscle where it appears to be in its autolysed state. The absence of any increase in enzyme activity, protein and mRNA abundance of calpains in aestivators is consistent with the protection of gastrocnemius muscle against uncontrolled proteolysis throughout aestivation.

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Calpain/calpastatin activities and substrate depletion patterns during hindlimb unweighting and reweighting in skeletal muscle

Cited by 67 publications

References 56 publications

Assessment of skeletal muscle proteolysis and the regulatory response to nutrition and exercise

Assessment of skeletal muscle proteolysis and the regulatory response to nutrition and exercise

Mechanisms underlying inhibition of muscle disuse atrophy during aestivation in the green-striped burrowing frog, Cyclorana alboguttata

Activity, abundance and expression of Ca2+-activated proteases in skeletal muscle of the aestivating frog, Cyclorana alboguttata

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