Heme oxygenase-1 expression in brain and lungs in hypobaric hypoxia exposed rabbits

Abstract

Exposure to high altitude (and thus hypobaric hypoxia) induces electrophysiological, metabolic, and morphological modifications in the different tissues, leading to oxidative stress and several clinical syndromes. Hypoxia is known to modulate a number of cellular metabolic functions, including what has been called the stress response. One of the stress response proteins is heme oxygenase-1 (НО-1), a ratelimiting enzyme in heme catabolism. It is responsible for converting a potential oxidant, heme, into a potential antioxidant, biliverdin, gaseous carbon monoxide, and free Fe2+. Heme oxygenase cleaves the heme ring at the alpha-methene bridge to form either biliverdin or, if the heme is still attached to a globin, verdoglobin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. The physiological role of HO-1 induction in hypoxia is still under investigation. It has been proposed that carbon monoxide resulting from HO-1 activity in hypoxic vascular smooth muscle cells plays a role in the regulation of the vessel tone via activation of soluble guanylyl cyclase. Using immunocytochemistry, this study demonstrates the developmental changes of HO-1 protein expression in brain and lungs endothelia from rabbits exposed to severe hypobaric hypoxia in a hypobaric chamber. The results of the study suggest that acute high-altitude hypoxia may serve as a model for oxidative stress and will aid in better understanding and management of hypoxia-induced pathologies.