Intermittent hypobaric
hypoxia can produce a protective effect on both the nervous system and non-nervous system tissues. Intermittent hypobaric
hypoxia preconditioning has been shown to protect rats from cardiac
ischemia-reperfusion injury by decreasing cardiac
iron levels and
reactive oxygen species (ROS) production, thereby decreasing oxidative stress to achieve protection. However, the specific mechanism underlying the protective effect of hypobaric
hypoxia is unclear. To shed light on this phenomenon, we subjected Sprague-Dawley rats to hypobaric hypoxic preconditioning (8 hours/day). The treatment was continued for 4 weeks. We then measured the
iron content in the heart, liver, spleen, and kidney. The
iron levels in all of the assessed tissues decreased significantly after hypobaric
hypoxia treatment, corroborating previous results that hypobaric
hypoxia may produce its protective effect by decreasing ROS production by limiting the levels of catalytic
iron in the tissue. We next assessed the expression levels of several
proteins involved in
iron metabolism (
transferrin receptor,
L-ferritin, and ferroportin1 [FPN1]). The increased
transferrin receptor and decreased
L-ferritin levels after hypobaric
hypoxia were indicative of a low-
iron phenotype, while FPN1 levels remained unchanged. We also examined
hepcidin, transmembrane
serine proteases 6 (TMPRSS6), erythroferrone (ERFE), and
erythropoietin (EPO) levels, all of which play a role in the regulation of systemic
iron metabolism. The expression of
hepcidin decreased significantly after hypobaric
hypoxia treatment, whereas the expression of TMPRSS6 and ERFE and EPO increased sharply. Finally, we measured serum
iron and total
iron binding capacity in the serum, as well as red blood cell count, mean corpuscular volume, hematocrit, red blood cell distribution width SD, and red blood cell distribution width CV. As expected, all of these values increased after the hypobaric
hypoxia treatment. Taken together, our results show that hypobaric
hypoxia can stimulate erythropoiesis, which systemically draws
iron away from nonhematopoietic tissue through decreased
hepcidin levels.