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. 2013 Mar;14(1):65-77.
doi: 10.1089/ham.2012.1064.

Upregulation of cytoprotective defense mechanisms and hypoxia-responsive proteins imparts tolerance to acute hypobaric hypoxia

Kanika Jain  1 , Geetha Suryakumar, Rajendra Prasad, Lilly Ganju
Affiliations

Upregulation of cytoprotective defense mechanisms and hypoxia-responsive proteins imparts tolerance to acute hypobaric hypoxia

Kanika Jain et al. High Alt Med Biol. 2013 Mar.

Abstract

Exposure to high altitude is a well-known environmental stress with physiological and metabolic consequences, with the major stressor being hypobaric hypoxia. The disruption in cellular homeostasis elicits several acute and chronic adaptations designed to diminish the stress imposed by the hypoxic insult. Highly conserved cellular machinery protects the myocardium from damage under reduced oxygen tension. In the present study, adult Sprague-Dawley rats were exposed to an altitude of 9754 m in a decompression chamber and screened on the basis of the time taken for onset of gasping. The animals were grouped as susceptible (<10 min), normal (10-25 min), and tolerant (>25 min). Histologically, susceptible animals showed increased myocardial inflammation and infiltration and greater CK-MB activity. These animals showed a three-fold increase in reactive oxygen species levels and subsequent oxidative damage to proteins and lipids as compared to control unexposed group. In tolerant animals, the damage was minimal. The resistance to damage in these animals was possibly due to enhanced myocardial antioxidant enzymes, catalase and superoxide dismutase. A significantly higher expression of HIF-1α and its responsive genes, including EPO, HO-1, and GLUT1, was seen in tolerant animals, although VEGF expression was enhanced in the susceptible group. Cytoprotective chaperones, HSP70 and HSP90, were elevated in the tolerant animals. The differential expression of these hypoxia-responsive molecules may thus act as potential biochemical markers for screening and identifying individuals susceptible to environmental stress.

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