Hepatic heme oxygenase is inducible in neonatal rats during the early postnatal period.
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 mumol/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 upregulation 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.
Tom
D J
DJ
Department of Pediatrics, Stanford University School of Medicine, California 94305, USA.
Rodgers
P A
PA
Shokoohi
V
V
Stevenson
D K
DK
Dennery
P A
PA
D000222:Adaptation, Physiological; D000818:Animals; D000831:Animals, Newborn; D004790:Enzyme Induction; D005293:Ferritins / Q000096:biosynthesis; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000201:enzymology* / Q000254:growth & development; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D005293:Ferritins; D006419:Heme Oxygenase (Decyclizing)