Hypobaric hypoxia mediated changes ill protein metabolism of skeletal muscle

Abstract

Exposure to high altitude hypoxia results in sustained muscle wasting. The present study is aimed at identifying the hind limb skeletal muscle more susceptible to hypobaric hypoxia and focused on understanding the molecular mechanisms that regulate skeletal muscle mass loss. The gastrocnemius muscle was found to be more susceptible to hypobaric hypoxia induced oxidative stress as reflected by increased levels of lipid peroxidation, free radical generation, protein carbonyl formation and nitric oxide levels. Gastrocnemius muscle also showed a significant depletion in the antioxidant status in addition to the increased oxidative stress. The evaluation of effects of acute and chronic hypobaric hypoxia on protein metabolism has shown that acute and chronic hypobaric hypoxia alters protein metabolism through different mechanisms. However, chronic hypobaric hypoxia leads to elevated skeletal muscle protein synthesis rate along with increased muscle proteolysis. It proves that synthesis rate is not a factor responsible for loss of skeletal muscle mass under chronic exposure. Chronic hypobaric hypoxia also resulted in loss of skeletal muscle integrity which was evident by decreased creatine phosphokinase activity in skeletal muscle homogenates. Histopathological studies provided significant evidence of skeletal muscle atrophy following different durations of exposure to chronic hypobaric hypoxia. The major protein affected during hypoxia is myosin heavy chain which constitutes the significant portion of myofibrillar proteins. NF-and#954;B has been found to be playing a significant role in muscle proteolysis. newlineThis study has also explored the dual role of curcumin as an anti-oxidant as well as inhibitor of NF-KB in preventing skeletal muscle mass loss following hypobaric hypoxia exposure.