Oxidative stress and disuse muscle atrophy

Powers, Scott K.; Kavazis, Andreas N.; McClung, Joseph M.

doi:10.1152/japplphysiol.01202.2006

Cited by 401 publications

(309 citation statements)

References 89 publications

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“…The degradation of myofibrillar proteins is a process that requires the coordination of several proteolytic systems, including the calpain, caspase-3 and the UPP. Specifically, it is predicted that the UPP is unable to cleave intact sarcomeric proteins and that release of these myofilaments from the sarcomeric lattice is required for UPP degradation of actin and myosin 40,43 .…”

Section: Discussionmentioning

confidence: 99%

“…Finally, in coordination with the E3 ligases, ubiquitin is attached to the protein substrate 44 . In reference to substrate recognition and degradation, expression of E2 and E3 ligases determines the specificity of the UPP and transcriptional levels of these proteins strongly correlates with muscle catabolism 40,43,44 . Further, expression of the muscle specific E3 ligases MuRF1 and atrogin-1/MaFbx has been reported to be essential for skeletal muscle atrophy 25-27 .…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of the Ubiquitin–Proteasome Pathway Does Not Protect against Ventilator-induced Accelerated Proteolysis or Atrophy in the Diaphragm

et al. 2014

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Background Mechanical ventilation (MV) is a life-saving intervention in patients with acute respiratory failure. However, prolonged MV results in ventilator-induced diaphragm dysfunction (VIDD), a condition characterized by both diaphragm fiber atrophy and contractile dysfunction. Previous work has shown calpain, caspase-3 and the ubiquitin-proteasome pathway (UPP) are all activated in the diaphragm during prolonged MV. However, while it is established that both calpain and caspase-3 are important contributors to VIDD, the role that the UPP plays in VIDD remains unknown. These experiments tested the hypothesis that inhibition of the UPP will protect the diaphragm against VIDD. Methods We tested this prediction in an established animal model of MV using a highly specific UPP inhibitor, epoxomicin, to prevent MV-induced activation of the proteasome in the diaphragm (n = 8/group). Results Our results reveal that inhibition of the UPP did not prevent ventilator-induced diaphragm muscle fiber atrophy and contractile dysfunction during 12 hours of MV. Also, inhibition of the UPP does not impact MV-induced increases in calpain and caspase-3 activity in the diaphragm. Finally, administration of the proteasome inhibitor did not protect against the MV-induced increases in the expression of the E3 ligases, MuRF1 and atrogin-1/MaFbx. Conclusions Collectively, these results indicate that proteasome activation does not play a required role in VIDD during the first 12 hours of MV.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of the Ubiquitin–Proteasome Pathway Does Not Protect against Ventilator-induced Accelerated Proteolysis or Atrophy in the Diaphragm

et al. 2014

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“…A possible mechanism underlying an enhanced protection against hypoxia in the zebrafish may be down-regulation of the rate of protein synthesis (Johnston and Bernard, 1982; Powers et al, 2007), which lowers the demand for oxygen in hypoxia. However, the unaffected growth of zebrafish muscle (hypertrophy) suggests that net protein synthesis rate in our zebrafish was likely not affected.…”

Section: Discussionmentioning

confidence: 99%

Increased oxidative metabolism and myoglobin expression in zebrafish muscle during chronic hypoxia

et al. 2014

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Fish may be extremely hypoxia resistant. We investigated how muscle fibre size and oxidative capacity in zebrafish (Danio rerio) adapt during severe chronic hypoxia. Zebrafish were kept for either 3 or 6 weeks under chronic constant hypoxia (CCH) (10% air/90%N2 saturated water). We analyzed cross-sectional area (CSA), succinate dehydrogenase (SDH) activity, capillarization, myonuclear density, myoglobin (Mb) concentration and Mb mRNA expression of high and low oxidative muscle fibres. After 3 weeks of CCH, CSA, SDH activity, Mb concentration, capillary and myonuclear density of both muscle fibre types were similar as under normoxia. In contrast, staining intensity for Mb mRNA of hypoxic high oxidative muscle fibres was 94% higher than that of normoxic controls (P<0.001). Between 3 and 6 weeks of CCH, CSA of high and low oxidative muscle fibres increased by 25 and 30%, respectively. This was similar to normoxic controls. Capillary and myonuclear density were not changed by CCH. However, in high oxidative muscle fibres of fish maintained under CCH, SDH activity, Mb concentration as well as Mb mRNA content were higher by 86%, 138% and 90%, respectively, than in muscle fibres of fish kept under normoxia (P<0.001). In low oxidative muscle fibres, SDH activity, Mb and Mb mRNA content were not significantly changed. Under normoxia, the calculated interstitial oxygen tension required to prevent anoxic cores in muscle fibres (PO2crit) of high oxidative muscle fibres was between 1.0 and 1.7 mmHg. These values were similar at 3 and 6 weeks CCH. We conclude that high oxidative skeletal muscle fibres of zebrafish continue to grow and increase oxidative capacity during CCH. Oxygen supply to mitochondria in these fibres may be facilitated by an increased Mb concentration, which is regulated by an increase in Mb mRNA content per myonucleus.

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“…In contrast, the IGF-1 signaling pathway is inhibited by higher levels of ROS and recent evidence suggests ROS down regulates the IGF-1 cascade and induces insulin resistance (Bashan et al, 2009; Figure 2). For detailed discussion of the signaling pathways linking ROS and muscle atrophy, the interested reader is referred to recent reviews on oxidative stress and disuse muscle atrophy (Pellegrino et al, 2011; Powers et al, 2011b, 2014; Zuo and Pannell, 2015). …”

Section: Introductionmentioning

confidence: 99%

Human Skeletal Muscle Disuse Atrophy: Effects on Muscle Protein Synthesis, Breakdown, and Insulin Resistance—A Qualitative Review

et al. 2016

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The ever increasing burden of an aging population and pandemic of metabolic syndrome worldwide demands further understanding of the modifiable risk factors in reducing disability and morbidity associated with these conditions. Disuse skeletal muscle atrophy (sometimes referred to as “simple” atrophy) and insulin resistance are “non-pathological” events resulting from sedentary behavior and periods of enforced immobilization e.g., due to fractures or elective orthopedic surgery. Yet, the processes and drivers regulating disuse atrophy and insulin resistance and the associated molecular events remain unclear—especially in humans. The aim of this review is to present current knowledge of relationships between muscle protein turnover, insulin resistance and muscle atrophy during disuse, principally in humans. Immobilization lowers fasted state muscle protein synthesis (MPS) and induces fed-state “anabolic resistance.” While a lack of dynamic measurements of muscle protein breakdown (MPB) precludes defining a definitive role for MPB in disuse atrophy, some proteolytic “marker” studies (e.g., MPB genes) suggest a potential early elevation. Immobilization also induces muscle insulin resistance (IR). Moreover, the trajectory of muscle atrophy appears to be accelerated in persistent IR states (e.g., Type II diabetes), suggesting IR may contribute to muscle disuse atrophy under these conditions. Nonetheless, the role of differences in insulin sensitivity across distinct muscle groups and its effects on rates of atrophy remains unclear. Multifaceted time-course studies into the collective role of insulin resistance and muscle protein turnover in the setting of disuse muscle atrophy, in humans, are needed to facilitate the development of appropriate countermeasures and efficacious rehabilitation protocols.

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Oxidative stress and disuse muscle atrophy

Abstract: Powers SK, Kavazis AN, McClung JM. Oxidative stress and disuse muscle atrophy.

Cited by 401 publications

References 89 publications

Inhibition of the Ubiquitin–Proteasome Pathway Does Not Protect against Ventilator-induced Accelerated Proteolysis or Atrophy in the Diaphragm

Inhibition of the Ubiquitin–Proteasome Pathway Does Not Protect against Ventilator-induced Accelerated Proteolysis or Atrophy in the Diaphragm

Increased oxidative metabolism and myoglobin expression in zebrafish muscle during chronic hypoxia

Human Skeletal Muscle Disuse Atrophy: Effects on Muscle Protein Synthesis, Breakdown, and Insulin Resistance—A Qualitative Review

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