Chronic hypobaric hypoxia mediated skeletal muscle atrophy: role of ubiquitin–proteasome pathway and calpains

Chaudhary, Pooja; Suryakumar, Geetha; Prasad, Rajendra; Singh, Som Nath; Ali, Shakir; Ilavazhagan, G.

doi:10.1007/s11010-011-1210-x

Cited by 87 publications

(71 citation statements)

References 39 publications

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“…The sustained activation status of protein synthesis and degradation and the continuous loss of tissue weight, compared with control and pair-fed animals, may reflect an elevated protein turnover and subsequent higher energy consumption under sustained hypoxic conditions. Although future studies should address actual protein synthesis and degradation rates and compare them to the observed changes in protein turnover signaling, elevated protein turnover rates in response to hypoxia described by Chaudhary et al (6) correspond with the increased expression of genes involved in protein turnover that we report here.…”

Section: L88supporting

confidence: 75%

“…It has been demonstrated previously that hypobaric hypoxia results in muscle atrophy (36,53). Although elevated protein turnover has been shown in rats under hypobaric hypoxia (6), changes in signaling pathways of protein synthesis and degradation were not investigated. Because hypobaric hypoxia involves effects of both oxygen limitation and barometric pressure reduction, the latter may confound the interpretation of the effects of hypoxia per se.…”

Section: L87 Hypoxia-induced Muscle Atrophy Modulates Protein Turnovementioning

confidence: 99%

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Distinct responses of protein turnover regulatory pathways in hypoxia- and semistarvation-induced muscle atrophy

Theije¹,

Langen

Lamers³

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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de Theije CC, Langen RC, Lamers WH, Schols AM, Köhler SE. Distinct responses of protein turnover regulatory pathways in hypoxia-and semistarvation-induced muscle atrophy. Am J Physiol Lung Cell Mol Physiol 305: L82-L91, 2013. First published April 26, 2013 doi:10.1152/ajplung.00354.2012.-The balance of muscle protein synthesis and degradation determines skeletal muscle mass. We hypothesized that hypoxia-induced muscle atrophy and alterations in the regulation of muscle protein turnover include a hypoxia-specific component, in addition to the observed effects of reduction in food intake in response to hypoxia. Mice were subjected to normoxic, hypoxic (8% oxygen), or pair-fed conditions for 2, 4, and 21 days. Cell-autonomous effects of hypoxia on skeletal muscle were also assessed in differentiated C2C12 myotubes. Hypoxia induced an initial rapid loss of body and muscle weight, which remained decreased during chronic hypoxia and could only in part be explained by the hypoxia-induced reduction of food intake (semistarvation). Regulatory steps of protein synthesis (unfolded protein response and mammal target of rapamycin signaling) remained active in response to acute and sustained hypoxia but not to semistarvation. Activation of regulatory signals for protein degradation, including increased expression of Murf1, Atrogin-1, Bnip3, and Map1lc3b mRNAs, was observed in response to acute hypoxia and to a lesser extent following semistarvation. Conversely, the sustained elevation of Atrogin-1, Bnip3, and Map1lc3b mRNAs and the increased activity of their upstream transcriptional regulator Forkhead box O1 were specific to chronic hypoxia because they were not observed in response to reduced food intake. In conclusion, altered regulation of protein turnover during hypoxia-induced muscle atrophy resulted from an interaction of semistarvation and a hypoxia-specific component. The finding that food restriction but not hypoxia-induced semistarvation inhibited regulatory steps in protein synthesis suggests a hypoxiaspecific impairment of the coordination between protein-synthesis signaling and protein-degradation signaling in skeletal muscle. hypoxia; mouse model; protein turnover; regulation; skeletal muscle WEIGHT LOSS AND MUSCLE ATROPHY are common features in advanced chronic obstructive pulmonary disease (COPD). In addition to nutritional imbalance, systemic inflammation, and progressive inactivity, hypoxemia has been implicated as a trigger for muscle atrophy in patients with COPD. Hypoxemia is a symptom during the whole course of the disease with chronic hypoxemia in end-stage COPD and acute hypoxemic episodes during exacerbations (50). Understanding the mechanisms by which hypoxia induces muscle atrophy will benefit the treatment of this disease because loss of muscle mass is a strong predictor of mortality and significantly increases disease burden (8,17,25,35,57). Although exposure to hypobaric hypoxia at high-altitudes results in muscle atrophy in men and animals (5,11,21,23), it is still under debate whether hypoba...

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Section: L88supporting

confidence: 75%

Section: L87 Hypoxia-induced Muscle Atrophy Modulates Protein Turnovementioning

confidence: 99%

Distinct responses of protein turnover regulatory pathways in hypoxia- and semistarvation-induced muscle atrophy

Theije¹,

Langen

Lamers³

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Although muscle atrophy in lung disease can be caused by several mechanisms discussed above (that is, sepsis, inflammation and reduced physical activity) (TABLE 1), other factors, especially hypoxia, may also contribute. Rats exposed to hypoxia showed decreased exercise capacity and muscle mass 149 and increased proteasome activity 150 . In humans, chronic exposure to high altitude is associated with decreased muscle mass 151 .…”

Section: Sarcopeniamentioning

confidence: 99%

Muscle wasting in disease: molecular mechanisms and promising therapies

Cohen

Nathan

Goldberg

2014

Nat Rev Drug Discov

878

850

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Atrophy occurs in specific muscles with inactivity (for example, during plaster cast immobilization) or denervation (for example, in patients with spinal cord injuries). Muscle wasting occurs systemically in older people (a condition known as sarcopenia); as a physiological response to fasting or malnutrition; and in many diseases, including chronic obstructive pulmonary disorder, cancer-associated cachexia, diabetes, renal failure, cardiac failure, Cushing syndrome, sepsis, burns and trauma. The rapid loss of muscle mass and strength primarily results from excessive protein breakdown, which is often accompanied by reduced protein synthesis. This loss of muscle function can lead to reduced quality of life, increased morbidity and mortality. Exercise is the only accepted approach to prevent or slow atrophy. However, several promising therapeutic agents are in development, and major advances in our understanding of the cellular mechanisms that regulate the protein balance in muscle include the identification of several cytokines, particularly myostatin, and a common transcriptional programme that promotes muscle wasting. Here, we discuss these new insights and the rationally designed therapies that are emerging to combat muscle wasting.

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“…Early studies associated the ascent and extended periods spent at high altitude (>5500 m) with up to a 15% muscle mass loss [45] and reduced strength gains (−6.4%) compared to normoxia [46]. Explanations for this have included altitude-induced protein synthesis rate reduction [47, 48] or increased protein degradation during exercise [49], leading to a negative synthesis/degradation of protein balance. Nevertheless, training camps are usually held at moderate altitudes (1800–2500 m), while no data are reported in scientific literature about hypertrophic resistance training during intermittent or chronic periods at terrestrial altitude; protein metabolism seems to be unaffected by O 2 availability at moderate simulated altitudes in acute NH [50].…”

Section: Hypertrophy Trainability In Conditions Of Hypoxiamentioning

confidence: 99%

Resistance Training Using Different Hypoxic Training Strategies: a Basis for Hypertrophy and Muscle Power Development

et al. 2017

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The possible muscular strength, hypertrophy, and muscle power benefits of resistance training under environmental conditions of hypoxia are currently being investigated.Nowadays, resistance training in hypoxia constitutes a promising new training strategy for strength and muscle gains. The main mechanisms responsible for these effects seem to be related to increased metabolite accumulation due to hypoxia. However, no data are reported in the literature to describe and compare the efficacy of the different hypertrophic resistance training strategies in hypoxia.Moreover, improvements in sprinting, jumping, or throwing performance have also been described at terrestrial altitude, encouraging research into the speed of explosive movements at altitude. It has been suggested that the reduction in the aerodynamic resistance and/or the increase in the anaerobic metabolism at higher altitudes can influence the metabolic cost, increase the take-off velocities, or improve the motor unit recruitment patterns, which may explain these improvements. Despite these findings, the applicability of altitude conditions in improving muscle power by resistance training remains to be clarified.This review examines current knowledge regarding resistance training in different types of hypoxia, focusing on strategies designed to improve muscle hypertrophy as well as power for explosive movements.

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Chronic hypobaric hypoxia mediated skeletal muscle atrophy: role of ubiquitin–proteasome pathway and calpains

Cited by 87 publications

References 39 publications

Distinct responses of protein turnover regulatory pathways in hypoxia- and semistarvation-induced muscle atrophy

Distinct responses of protein turnover regulatory pathways in hypoxia- and semistarvation-induced muscle atrophy

Muscle wasting in disease: molecular mechanisms and promising therapies

Resistance Training Using Different Hypoxic Training Strategies: a Basis for Hypertrophy and Muscle Power Development

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