Mechanisms of disuse muscle atrophy: role of oxidative stress

Powers, Scott K.; Kavazis, Andreas N.; DeRuisseau, Keith C.

doi:10.1152/ajpregu.00469.2004

Cited by 316 publications

(296 citation statements)

References 60 publications

(99 reference statements)

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“…Muscle wasting in the above‐mentioned conditions also involves ROS production, which has been found to be associated with protein catabolism and ubiquitin‐proteasome pathway (Li & Reid, 2000; Gomes‐Marcondes & Tisdale, 2002). In addition, oxidative stress during aging is considered to be a major contributor of muscle atrophy (Sohal & Weindruch, 1996; Powers et al. , 2005).…”

Section: Discussionmentioning

confidence: 99%

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Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF‐κB

et al. 2011

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SummaryAbnormal levels of reactive oxygen species (ROS) and inflammatory cytokines have been observed in the skeletal muscle during muscle wasting including sarcopenia. However, the mechanisms that signal ROS production and prolonged maintenance of ROS levels during muscle wasting are not fully understood. Here, we show that myostatin (Mstn) is a pro‐oxidant and signals the generation of ROS in muscle cells. Myostatin, a transforming growth factor‐β (TGF‐β) family member, has been shown to play an important role in skeletal muscle wasting by increasing protein degradation. Our results here show that Mstn induces oxidative stress by producing ROS in skeletal muscle cells through tumor necrosis factor‐α (TNF‐α) signaling via NF‐κB and NADPH oxidase. Aged Mstn null (Mstn−/−) muscles, which display reduced sarcopenia, also show an increased basal antioxidant enzyme (AOE) levels and lower NF‐κB levels indicating efficient scavenging of excess ROS. Additionally, our results indicate that both TNF‐α and hydrogen peroxide (H2O2) are potent inducers of Mstn and require NF‐κB signaling for Mstn induction. These results demonstrate that Mstn and TNF‐α are components of a feed forward loop in which Mstn triggers the generation of second messenger ROS, mediated by TNF‐α and NADPH oxidase, and the elevated TNF‐α in turn stimulates Mstn expression. Higher levels of Mstn in turn induce muscle wasting by activating proteasomal‐mediated catabolism of intracellular proteins. Thus, we propose that inhibition of ROS induced by Mstn could lead to reduced muscle wasting during sarcopenia.

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Section: Discussionmentioning

confidence: 99%

“…Several studies have reported an increase in reactive oxygen species (ROS) in muscle in response to infection, inflammatory stimulus and/or aging (Sohal & Weindruch, 1996; Powers et al. , 2005).…”

Section: Introductionmentioning

confidence: 99%

Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF‐κB

et al. 2011

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“…In addition to its role in mitochondrialdependent and mitochondrial-independent mediated apoptosis, caspase-3 also serves as a protease involved in myofibrillar protein release, resulting in contractile protein proteolysis (10). Therefore, inhibition of caspase-3 during MV may result in the retardation of myofilament release associated with myofiber atrophy in this model.…”

Section: Mv-induced Myonuclear Apoptosismentioning

confidence: 91%

“…In addition to myofibrillar protein loss, extracellular matrix expansion, and metabolic enzyme alterations (9)(10)(11), prolonged disuse of skeletal muscle results in the selective loss of myonuclei (12)(13)(14)(15)(16). Myonuclear loss may be a strategy used by the fiber to maintain a constant ratio of cytoplasmic myofiber volume per myonucleus (i.e., myonuclear domain) (16).…”

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confidence: 99%

“…Numerous cellular mechanisms lead to caspase-3 activation, including mitochondrial-dependent (cytochrome c release) and mitochondrial-independent (e.g., Ca 2ϩ activation of calpain) pathways resulting in the stimulation of DNases responsible for cellular DNA fragmentation and protein degradation (19). Oxidative stress occurs rapidly in the diaphragm during mechanical ventilation (18), and oxidant stress can promote cytochrome c release and cellular Ca 2ϩ overload in cells (10,20). This fact suggests a potential role for caspase-3 activation in the regulation of myonuclear number during the rapid atrophy that occurs in the diaphragm after prolonged MV.…”

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confidence: 99%

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Caspase-3 Regulation of Diaphragm Myonuclear Domain during Mechanical Ventilation–induced Atrophy

McClung

Kavazis

DeRuisseau

et al. 2007

Am J Respir Crit Care Med

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162

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Rationale: Unloading the diaphragm via mechanical ventilation (MV) results in rapid diaphragmatic fiber atrophy. It is unknown whether the myonuclear domain (cytoplasmic myofiber volume/ myonucleus) of diaphragm myofibers is altered during MV. Objective: We tested the hypothesis that MV-induced diaphragmatic atrophy is associated with a loss of myonuclei via a caspase-3-mediated, apoptotic-like mechanism resulting in a constant myonuclear domain. Methods: To test this postulate, Sprague-Dawley rats were randomly assigned to a control group or to experimental groups exposed to 6 or 12 h of MV with or without administration of a caspase-3 inhibitor. Measurements and Main Results:After 12 h of MV, type I and type IIa diaphragm myofiber areas were decreased by 17 and 23%, respectively, and caspase-3 inhibition attenuated this decrease. Diaphragmatic myonuclear content decreased after 12 h of MV and resulted in the maintenance of a constant myonuclear domain in all fiber types. Both 6 and 12 h of MV resulted in caspase-3-dependent increases in apoptotic markers in the diaphragm (e.g., number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positive nuclei and DNA fragmentation). Caspase-3-dependent increases in apoptotic markers occurred after 6 h of MV, before the onset of myofiber atrophy. Conclusions: Collectively, these data support the hypothesis that the myonuclear domain of diaphragm myofibers is maintained during prolonged MV and that caspase-3-mediated myonuclear apoptosis contributes to this process. Keywords: muscle atrophy; respiratory muscle; apoptosis; ventilatory weaning Mechanical ventilation (MV) is a clinical intervention for patients who are unable to maintain adequate alveolar ventilation. Recent evidence reveals that controlled MV results in a swift progression of diaphragmatic atrophy and weakness (1-6). It seems that this diaphragmatic atrophy and weakness contributes to difficulty in weaning patients from the ventilator (7). The mechanism(s) responsible for the rapid onset of diaphragmatic atrophy and weakness are not fully understood. Therefore, delineating these mechanisms is a prerequisite for the development of therapeutic strategies to circumvent weaning difficulties. Although mechanical ventilation-induced diaphragm inactivity results in fiber atrophy, it is unknown if prolonged mechanical ventilation is associated with alterations in myonuclear domain via apoptotic mechanisms. What This Study Adds to the FieldOur results reveal that inhibiting caspase-3 activation and myonuclear loss during mechanical ventilation attenuates diaphragmatic muscle atrophy.Mechanical ventilation-induced diaphragmatic atrophy and contractile dysfunction is characterized by oxidative stress and stress-related gene expression in myofibers that occurs within a matter of hours (7,8). In addition to myofibrillar protein loss, extracellular matrix expansion, and metabolic enzyme alterations (9-11), prolonged disuse of skeletal muscle results in the selective loss of myonuclei (12-16). Myonu...

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Chronic Obstructive Pulmonary Disease and Oxidative Damage

Barreiro

2017

Protein Carbonylation

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Mechanisms of disuse muscle atrophy: role of oxidative stress

Cited by 316 publications

References 60 publications

Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF‐κB

Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF‐κB

Caspase-3 Regulation of Diaphragm Myonuclear Domain during Mechanical Ventilation–induced Atrophy

Chronic Obstructive Pulmonary Disease and Oxidative Damage

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