The Proteolytic Systems of Muscle Wasting

Scicchitano, Bianca Maria; Faraldi, Martina; Musarò, Antonio

doi:10.2174/2352092209999150911121502

Cited by 16 publications

(20 citation statements)

References 127 publications

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“…Instead, indirect studies of protein degradation pathways have to be employed to measure molecular markers of muscle proteolysis. The major protein degradation pathways in skeletal muscle include the Ca 2+ -dependent proteases, lysosomal system, caspases and ubiquitin proteasome pathways (Scicchitano et al, 2015 ). It was proposed that Ca 2+ -dependent proteases (calpains) act as a promoter of muscle protein degradation, and might be responsible for the discharge of myofilaments from the surface of myofibrils (Dayton et al, 1976 ).…”

Section: Mechanisms Of Muscle Atrophymentioning

confidence: 99%

“…Emerging evidence suggests that calpains (Huang and Zhu, 2016 ), caspase-3 (Talbert et al, 2013 ), autophagy-lysosomal system (Sandri, 2010 ) and ubiquitin proteasome pathway (Bodine and Baehr, 2014 ), all are involved in disuse-induced muscle atrophy. However, the ubiquitin proteasome system is often considered as the most important proteolytic system during disuse conditions that promotes muscle wasting (Scicchitano et al, 2015 ; Baehr et al, 2017 ). The breakdown of protein via the ubiquitin proteasome system requires three distinct enzymatic components of the ubiquitin proteasome pathway: E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme) and E3 (ubiquitin ligase, key enzyme which regulates proteolysis as it recognizes multiple target protein substrates).…”

Section: Mechanisms Of Muscle Atrophymentioning

confidence: 99%

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Muscle Atrophy Induced by Mechanical Unloading: Mechanisms and Potential Countermeasures

et al. 2018

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Prolonged periods of skeletal muscle inactivity or mechanical unloading (bed rest, hindlimb unloading, immobilization, spaceflight and reduced step) can result in a significant loss of musculoskeletal mass, size and strength which ultimately lead to muscle atrophy. With advancement in understanding of the molecular and cellular mechanisms involved in disuse skeletal muscle atrophy, several different signaling pathways have been studied to understand their regulatory role in this process. However, substantial gaps exist in our understanding of the regulatory mechanisms involved, as well as their functional significance. This review aims to update the current state of knowledge and the underlying cellular mechanisms related to skeletal muscle loss during a variety of unloading conditions, both in humans and animals. Recent advancements in understanding of cellular and molecular mechanisms, including IGF1-Akt-mTOR, MuRF1/MAFbx, FOXO, and potential triggers of disuse atrophy, such as calcium overload and ROS overproduction, as well as their role in skeletal muscle protein adaptation to disuse is emphasized. We have also elaborated potential therapeutic countermeasures that have shown promising results in preventing and restoring disuse-induced muscle loss. Finally, identified are the key challenges in this field as well as some future prospectives.

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Section: Mechanisms Of Muscle Atrophymentioning

confidence: 99%

Section: Mechanisms Of Muscle Atrophymentioning

confidence: 99%

Muscle Atrophy Induced by Mechanical Unloading: Mechanisms and Potential Countermeasures

et al. 2018

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“…The proteolytic systems contributing to muscle atrophy are the ubiquitinproteasome system (UPS), the lysosomal system (autophagy), the calpain system, and apoptosis. (28) Cisplatin, another platinum-based chemotherapy drug, caused a decrease in C2C12 myotube diameter and increased markers of autophagy and apoptosis. (29) Cisplatin also induces muscle atrophy via UPS-mediated protein degradation and decreases in protein kinase B (Akt) and forkhead box O3a (Foxo3a) phosphorylation in mice.…”

Section: Introductionmentioning

confidence: 99%

Zoledronic Acid Improves Muscle Function in Healthy Mice Treated with Chemotherapy

Hain

Jude

et al. 2019

Journal of Bone and Mineral Research

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Carboplatin is a chemotherapy drug used to treat solid tumors but also causes bone loss and muscle atrophy and weakness. Bone loss contributes to muscle weakness through bone-muscle crosstalk, which is prevented with the bisphosphonate zoledronic acid (ZA). We treated mice with carboplatin in the presence or absence of ZA to assess the impact of bone resorption on muscle. Carboplatin caused loss of body weight, muscle mass, and bone mass, and also led to muscle weakness as early as 7 days after treatment. Mice treated with carboplatin and ZA lost body weight and muscle mass but did not lose bone mass. In addition, muscle function in mice treated with ZA was similar to control animals. We also used the anti-TGFβ antibody (1D11) to prevent carboplatin-induced bone loss and showed similar results to ZA-treated mice. We found that atrogin-1 mRNA expression was increased in muscle from mice treated with carboplatin, which explained muscle atrophy. In mice treated with carboplatin for 1 or 3 days, we did not observe any bone or muscle loss, or muscle weakness. In addition, reduced caloric intake in the carboplatin treated mice did not cause loss of bone or muscle mass, or muscle weakness. Our results show that blocking carboplatin-induced bone resorption is sufficient to prevent skeletal muscle weakness and suggests another benefit to bone therapy beyond bone in patients receiving chemotherapy.n 368 HAIN ET AL. TissueMice were euthanized and the tibialis anterior (TA), soleus, and gastrocnemius were dissected. The extensor digitorum longus (EDL) muscle was dissected for muscle contractility. Muscles were either snap frozen in liquid nitrogen for biochemical analysis or embedded in optimum cutting temperature (O.C.T., Tissue Tek, Torrance, CA, USA) compound in cryomolds and frozen in liquid nitrogencooled 2-methylbutane (isopentane) for histological analysis. (38) Journal of Bone and Mineral Research ZA IMPROVES MUSCLE FUNCTION IN HEALTHY MICE TREATED WITH CHEMOTHERAPY 369 n 40. Wen Y, Murach KA, Vechetti IJ Jr, et al. MyoVision: software for automated high-content analysis of skeletal muscle immunohistochemistry. J Appl Physiol. 2018;124(1):40-51. 41. Edwards JR, Nyman JS, Lwin ST, et al. Inhibition of TGF-beta signaling by 1D11 antibody treatment increases bone mass and quality in vivo.

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“…Extreme or pathologic conditions generate much higher levels of ROS that overwhelm cellular antioxidant defenses, leading to protein carbonylation, DNA damage, and RNA oxidation. The excess of ROS production can also alter calcium handling, another pathogenic factor associated with muscular dystrophy, leading to the activation of proteolytic systems and muscle wasting [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Increased Circulating Levels of Interleukin‐6 Induce Perturbation in Redox‐Regulated Signaling Cascades in Muscle of Dystrophic Mice

Pelosi

Forcina

Nicoletti

et al. 2017

Oxidative Medicine and Cellular Longevity

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Duchenne muscular dystrophy (DMD) is an X-linked genetic disease in which dystrophin gene is mutated, resulting in dysfunctional or absent dystrophin protein. The pathology of dystrophic muscle includes degeneration, necrosis with inflammatory cell invasion, regeneration, and fibrous and fatty changes. Nevertheless, the mechanisms by which the absence of dystrophin leads to muscle degeneration remain to be fully elucidated. An imbalance between oxidant and antioxidant systems has been proposed as a secondary effect of DMD. However, the significance and precise extent of the perturbation in redox signaling cascades is poorly understood. We report that mdx dystrophic mice are able to activate a compensatory antioxidant response at the presymptomatic stage of the disease. In contrast, increased circulating levels of IL-6 perturb the redox signaling cascade, even prior to the necrotic stage, leading to severe features and progressive nature of muscular dystrophy.

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The Proteolytic Systems of Muscle Wasting

Cited by 16 publications

References 127 publications

Muscle Atrophy Induced by Mechanical Unloading: Mechanisms and Potential Countermeasures

Muscle Atrophy Induced by Mechanical Unloading: Mechanisms and Potential Countermeasures

Zoledronic Acid Improves Muscle Function in Healthy Mice Treated with Chemotherapy

Increased Circulating Levels of Interleukin‐6 Induce Perturbation in Redox‐Regulated Signaling Cascades in Muscle of Dystrophic Mice

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