Molecular and Cellular Biochemistry

, Volume 364, Issue 1–2, pp 101–113

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

  • Pooja Chaudhary
  • Geetha Suryakumar
  • Rajendra Prasad
  • Som Nath Singh
  • Shakir Ali
  • Govindsamy Ilavazhagan
Article

Abstract

The most frequently reported symptom of exposure to high altitude is loss of body mass and decreased performance which has been attributed to altered protein metabolism affecting skeletal muscles mass. The present study explores the mechanism of chronic hypobaric hypoxia mediated skeletal muscle wasting by evaluating changes in protein turnover and various proteolytic pathways. Male Sprague–Dawley rats weighing about 200 g were exposed to hypobaric hypoxia (7,620 m) for different durations of exposure. Physical performance of rats was measured by treadmill running experiments. Protein synthesis, protein degradation rates were determined by 14C-Leucine incorporation and tyrosine release, respectively. Chymotrypsin-like enzyme activity of the ubiquitin–proteasome pathway and calpains were studied fluorimetrically as well as using western blots. Declined physical performance by more than 20%, in terms of time taken in exhaustion on treadmill, following chronic hypobaric hypoxia was observed. Compared to 1.5-fold increase in protein synthesis, the increase in protein degradation was much higher (five-folds), which consequently resulted in skeletal muscle mass loss. Myofibrillar protein level declined from 46.79 ± 1.49 mg/g tissue at sea level to 37.36 ± 1.153 (P < 0.05) at high altitude. However, the reduction in sarcoplasmic proteins was less as compared to myofibrillar protein. Upregulation of Ub-proteasome pathway (five-fold over control) and calpains (three-fold) has been found to be important factors for the enhanced protein degradation rate. The study provided strong evidences suggesting that elevated protein turnover rate lead to skeletal muscle atrophy under chronic hypobaric hypoxia via ubiquitin–proteasome pathway and calpains.

Keywords

Hypobaric hypoxia Muscle atrophy Protein turnover Ubiquitin–proteasome pathway 

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Pooja Chaudhary
    • 1
  • Geetha Suryakumar
    • 1
  • Rajendra Prasad
    • 1
  • Som Nath Singh
    • 1
  • Shakir Ali
    • 2
  • Govindsamy Ilavazhagan
    • 1
  1. 1.Defence Institute of Physiology and Allied SciencesNew DelhiIndia
  2. 2.Department of BiochemistryJamia HamdardNew DelhiIndia

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