HEPATIC HEME OXYGENASE IS INDUCIBLE IN NEONATAL RATS DURING THE EARLYPOSTNATAL-PERIOD

Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of h eme to bilirubin. Cobalt chloride (CoCl2) and many other agents that g enerate oxidant stresses induce the HO-1 isoform. Furthermore, HO-1 ha s 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 po stnatal period, and whether HO-1 induction is associated with increase d ferritin synthesis in neonates. Therefore, we studied hepatic HO-1 m RNA, HO-1 protein concentration, total HO activity, and ferritin prote in levels in neonatal rats. Neonatal rats 0-5 d of age were injected w ith 250 mu mol/kg body weight of CoCl2 . 6H(2)O in saline or with an e qual volume of saline in age-matched controls. Liver samples were coll ected 4 h after injection for HO-1 mRNA analysis and 20 h after inject ion 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 concen tration 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). The re were no differences in hepatic ferritin protein levels between CoCl 2-treated neonatal rats and controls; however, in CoCl2-treated adult rats, hepatic ferritin protein levels were 1.6 times the levels in con trols (p < 0.05). Thus, neonatal rats can up-regulate hepatic HO-1 mRN A, HO-1 protein concentration, and total HO activity in response to Co Cl2; however, no upregulation of hepatic ferritin protein levels was o bserved in neonatal rats after CoCl2 administration or subsequent HO-1 induction. We speculate;hat neonatal rats induce hepatic HO-1 and up- regulate ferritin by different mechanisms than do adult rats.