Heme Oxygenase Activity in Fetal and Adult Ovine Tissue: Effects of High altitude-induced Long-term Hypoxemia
Conference Contribution ResearchOnline@JCUAbstract
Background: Heme oxygenases (HO, EC 1.14.99.3) are involved in the biotransformation of heme to bilverdin/bilirubin, ferrous iron and carbon monoxide (CO). It is known that products of heme catabolism play a role in the regulation of many physiological processes including vascular tone, inflammatory responses and central nervous system function. The HO system is also involved in cytoprotection against oxidative stress. In mammals, there are two catalytically functional HO isozymes, HO-1 (inducible) and HO-2 (constitutive). The expression and function of HO and particularly HO-1, is regulated by an array of physiological and non-physiological including the exposure to heavy metals, ionizing radiation and acute hypoxemia. As relatively little is known of the HO response response to prolonged hypoxemia in whole animals other than small laboratory rodents, we examined the effect of long-term hypoxemia on total HO activity in fetal and adult ovine tissue. Methods: Sheep were maintained at high altitude (3,820 m) after which the following tissues were harvested from near term fetal and non-pregnant adult ewes for in vitro measurement of HO activity: left heart ventricle, renal papilla, lung apex, pulmonary artery, carotid artery, mesenteric artery, placental cotyledon, spleen and brain frontal cortex. Relative HO-1 and HO-2 protein expression was quantified by sodium dodecyl sulfate polyacrylamide gel electrophoresis and HO activity was measured by quantitation of CO using gas chromatography. Results and conclusions: HO activity was detected in all the tissues examined but there were no significant differences between hypoxic fetal and adult sheep compared to their normoxic controls. Fetal heart HO activities were higher than those of adult sheep (P < 0.05), while spleen HO activity was significantly higher than that of fetal tissue (P < 0.05). These data indicate that high altitude-induced hypoxemia does not have a persistent effect on HO activity in ovine tissues. Also except for the spleen where there is a high expression of HO-1, under normal conditions, tissue HO activity is correlated with the expression of HO-2, the constitutive enzyme. In some body tissues such as the heart and spleen, HO expression and enzymatic activity may be developmentally regulated. (This work was supported by the Canadian Institutes of Health Research Grant MOP 64305 and National Institute of Health Research Grant PO1-HD-31226).
Journal
Pediatric Research
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Volume
58
ISBN/ISSN
1530-0447
Edition
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Issue
5
Pages Count
1
Location
Toronto, Canada
Publisher
Springer
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EISSN
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DOI
10.1203/00006450-200511000-00033