Redox Control of Proteolysis During Inactivity-Induced Skeletal Muscle Atrophy

Powers, Scott K.; Özdemir, Merve; Hyatt, Hayden W.

doi:10.1089/ars.2019.8000

Cited by 36 publications

(41 citation statements)

References 111 publications

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“…VIDD occurs within the first 12–18 h of prolonged MV in both humans and animals as evidenced by a 15–20% reduction in both diaphragm fiber size and specific force production [ [2] , [3] , [4] ]. While previous studies have demonstrated that this rapid rate of MV-induced diaphragmatic muscle atrophy is driven by accelerated proteolysis [ 42 , 45 , 46 ], the current experiments provide the first robust evidence that activation of calpain is essential for the occurrence of VIDD. Indeed, because the only known function of CAST is to inhibit calpain, our results confirm that prevention of MV-induced activation of calpain protects the diaphragm against MV-induced reductions in both fiber CSA and contractile forces.…”

Section: Discussionmentioning

confidence: 47%

Calpains play an essential role in mechanical ventilation-induced diaphragmatic weakness and mitochondrial dysfunction

et al. 2021

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Section: Discussionmentioning

confidence: 47%

Calpains play an essential role in mechanical ventilation-induced diaphragmatic weakness and mitochondrial dysfunction

et al. 2021

Self Cite

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“…This is important because increased proton leak can augment oxidant production within the mitochondrial matrix leading to a disruption of redox balance within the muscle tissue [33,34]. Oxidative stress is a wellestablished upstream trigger sufficient to promote muscle catabolism and dysfunction in a variety of conditions [35]. Increased protein oxidation in muscle tissue results in alterations to structure and function, which enhances proteolytic breakdown by calpain, caspase-3, the ubiquitinproteasome system and the autophagy/lysosomal system [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological targeting of mitochondrial function and reactive oxygen species production prevents colon 26 cancer-induced cardiorespiratory muscle weakness

et al. 2020

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Cancer cachexia is a syndrome characterized by profound cardiac and diaphragm muscle wasting, which increase the risk of morbidity in cancer patients due to failure of the cardiorespiratory system. In this regard, muscle relies greatly on mitochondria to meet energy requirements for contraction and mitochondrial dysfunction can result in muscle weakness and fatigue. In addition, mitochondria are a major source of reactive oxygen species (ROS) production, which can stimulate increased rates of muscle protein degradation. Therefore, it has been suggested that mitochondrial dysfunction may be an underlying factor that contributes to the pathology of cancer cachexia. To determine if pharmacologically targeting mitochondrial dysfunction via treatment with the mitochondria-targeting peptide SS-31 would prevent cardiorespiratory muscle dysfunction, colon 26 (C26) adenocarcinoma tumor-bearing mice were administered either saline or SS-31 daily (3 mg/kg/day) following inoculation. C26 mice treated with saline demonstrated greater ROS production and mitochondrial uncoupling compared to C26 mice receiving SS-31 in both the heart and diaphragm muscle. In addition, saline-treated C26 mice exhibited a decline in left ventricular function which was significantly rescued in C26 mice treated with SS-31. In the diaphragm, muscle fiber cross-sectional area of C26 mice treated with saline was significantly reduced and force production was impaired compared to C26, SS-31-treated animals. Finally, ventilatory deficits were also attenuated in C26 mice treated with SS-31, compared to saline treatment. These data demonstrate that C26 tumors promote severe cardiac and respiratory myopathy, and that prevention of mitochondrial dysfunction is sufficient to preclude cancer cachexia-induced cardiorespiratory dysfunction. Author contributions AJS, HHS and ARJ designed the study. AJS, BMR, MPW, OK, JY, DDC and DDF performed the experiments and analyzed the data. HHS provided the SS-31. AJS and ARJ wrote the manuscript. All authors reviewed and approved the final version of the manuscript.

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“…Oxidative stress is thought as an atrophic mechanism that can modulate other mechanisms. For example, the ubiquitin proteasome system (UPS), calpains, or autophagy-lysosomal system are upregulated by ROS, while the anabolic pathway is inhibited by ROS [64,[68][69][70][71]. Brown et al [72] examined mitochondrial degeneration during the progression of cancer cachexia in two male mouse models, the Lewis lung carcinoma implantation model and the genetic Apc Min/+ colorectal cancer model.…”

Section: Sex Differences In Muscle Mitochondrial Metabolismmentioning

confidence: 99%

Sex Differences in Cancer Cachexia

Zhong

Zimmers

2020

Curr Osteoporos Rep

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Purpose of Review Cachexia, a feature of cancer and other chronic diseases, is marked by progressive weight loss and skeletal muscle wasting. This review aims to highlight the sex differences in manifestations of cancer cachexia in patients, rodent models, and our current understanding of the potential mechanisms accounting for these differences. Recent Findings Male cancer patients generally have higher prevalence of cachexia, greater weight loss or muscle wasting, and worse outcomes compared with female cancer patients. Knowledge is increasing about sex differences in muscle fiber type and function, mitochondrial metabolism, global gene expression and signaling pathways, and regulatory mechanisms at the levels of sex chromosomes vs. sex hormones; however, it is largely undetermined how such sex differences directly affect the susceptibility to stressors leading to muscle wasting in cancer cachexia. Summary Few studies have investigated basic mechanisms underlying sex differences in cancer cachexia. A better understanding of sex differences would improve cachexia treatment in both sexes.

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Redox Control of Proteolysis During Inactivity-Induced Skeletal Muscle Atrophy

Cited by 36 publications

References 111 publications

Calpains play an essential role in mechanical ventilation-induced diaphragmatic weakness and mitochondrial dysfunction

Calpains play an essential role in mechanical ventilation-induced diaphragmatic weakness and mitochondrial dysfunction

Pharmacological targeting of mitochondrial function and reactive oxygen species production prevents colon 26 cancer-induced cardiorespiratory muscle weakness

Sex Differences in Cancer Cachexia

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