Abstract
Heme oxygenase (HO), the rate-limiting enzyme in the formation of bilirubin, is expressed in the lung and may serve as an antioxidant. This enzyme results in the formation of antioxidant bile pigments and the degradation of pro-oxidant heme. We wanted to evaluate the differences in expression of HO-1, the inducible form, and HO-2, the constitutive isoenzyme, during lung maturation and document whether lung HO expression was similar to that of other antioxidant enzymes. Lung total HO activity and HO-1 and HO-2 proteins as well as HO-1 and HO-2 mRNA were evaluated in animals from 16 d of gestation (e16.5) to 2 mo of age. Heme content was also evaluated because heme is the substrate of the reaction. HO-1 mRNA was maximal at e19.5 and e20.5, whereas HO-2 mRNA was not changed throughout maturation. Lung HO-1 protein was highest on the first days of life and lowest in adults, whereas HO-2 protein was maximally expressed at postnatal d 5 and then declined to reach adult values. As to HO activity, there was a prenatal peak at e20.5, a second lesser peak at d 5, and thereafter a decline to adult values. Lung heme content was inversely correlated with HO activity or protein as the highest heme values were seen in adults with the lowest HO activity. In response to hyperoxia, HO-1 mRNA was induced only in the adult lungs. A better understanding of the maturational regulation of lung HO will define a role for HO in newborns at risk for oxygen toxicity.
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Abbreviations
- HO:
-
heme oxygenase
- en:
-
day (n) of embryonic life
- VeCO:
-
excretion of carbon monoxide
- GAPD:
-
glyceraldehyde-3-phosphate dehydrogenase
- dCTP:
-
deoxyribocytosine-triphosphate
- AOE:
-
antioxidant enzyme
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Acknowledgements
We thank Arthur Tatarov for his expert technical assistance and Lisa Raskin for preparing the slides for immunohistochemistry.
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Supported by the National Institutes of Health Grant HL-52701 and HL-58752 (P.A.D.) and the Mary L. Johnson and Hess and Court Ballanger funds of Stanford University.
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Dennery, P., Lee, C., Ford, B. et al. Developmental Expression of Heme Oxygenase in the Rat Lung. Pediatr Res 53, 42–47 (2003). https://doi.org/10.1203/00006450-200301000-00010
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DOI: https://doi.org/10.1203/00006450-200301000-00010
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