Abstract
Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme to bilirubin. Cobalt chloride (CoCl2) and many other agents that generate oxidant stresses induce the HO-1 isoform. Furthermore, HO-1 has been shown to protect against oxidant stress in vitro and in vivo by mechanisms involving increased ferritin synthesis. However, little is known about the inducibility of hepatic HO-1 during the very early postnatal period, and whether HO-1 induction is associated with increased ferritin synthesis in neonates. Therefore, we studied hepatic HO-1 mRNA, HO-1 protein concentration, total HO activity, and ferritin protein levels in neonatal rats. Neonatal rats 0-5 d of age were injected with 250 μmol/kg body weight of CoCl2 · 6H2O in saline or with an equal volume of saline in age-matched controls. Liver samples were collected 4 h after injection for HO-1 mRNA analysis and 20 h after injection for analysis of HO-1 protein concentration, total HO activity, and ferritin protein levels. In CoCl2-treated rats, hepatic HO-1 mRNA was 3-10 times the levels in control rats (p < 0.05), HO-1 protein concentration was 2-5 times the levels in control rats (p < 0.05), and total HO activity was higher by 20-80% than in control rats (p < 0.05). There were no differences in hepatic ferritin protein levels between CoCl2-treated neonatal rats and controls; however, in CoCl2-treated adult rats, hepatic ferritin protein levels were 1.6 times the levels in controls(p < 0.05). Thus, neonatal rats can up-regulate hepatic HO-1 mRNA. HO-1 protein concentration, and total HO activity in response to CoCl2; however, no up-regulation of hepatic ferritin protein levels was observed in neonatal rats after CoCl2 administration or subsequent HO-1 induction. We speculate that neonatal rats induce hepatic HO-1 and up-regulate ferritin by different mechanisms than do adult rats.
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Abbreviations
- HO:
-
heme oxygenase
- GSH:
-
glutathione
- GAPDH:
-
glyceraldehyde-3-phosphate dehydrogenase
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This work was done while Dr. Tom was a postdoctoral fellow in the Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine.
Supported by National Institutes of Health (NIH) Grant HD 01124, NIH Training Grant HD 07249, NIH Grant HD 14426, and the Mary L. Johnson Research Fund.
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Tom, D., Rodgers, P., Shokoohi, V. et al. Hepatic Heme Oxygenase Is Inducible in Neonatal Rats during the Early Postnatal Period. Pediatr Res 40, 288–293 (1996). https://doi.org/10.1203/00006450-199608000-00016
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DOI: https://doi.org/10.1203/00006450-199608000-00016
