Dynamic Changes of Heme Oxygenase-1 in the Hippocampus of Rats After Acute Carbon Monoxide Poisoning

Heme oxygenase-1 (HO-1), an inducible enzyme, degrades heme to carbon monoxide (CO), iron, and bilirubin. We have investigated the relationship among HO-1 protein expression, HO activity, and CO concentrations in the hippocampus of CO-exposed rats. Western blotting and immunohistochemistry revealed that the enzyme is predominantly localized in hippocampal CA1 and CA3 pyramidal cells and in granule cells of the dentate gyrus. HO enzyme activity was reduced immediately following CO exposure, while expression of HO-1 protein was consistently upregulated in a time-dependent manner. Local CO concentrations in hippocampus rose immediately following exposure, but the elevation was maintained for ~20 h despite the decline in blood carboxyhemoglobin levels toward baseline. We suggest that CO initially inhibits HO enzyme activity, whereas at later time points the inhibition is released and local CO generation is maintained by the activity of the endogenous HO enzyme. And the noninducible form of heme oxygenase, HO-2, was not altered following CO administration. Together these results indicate that the HO/CO pathway in the rat hippocampus is induced by acute CO exposure; local CO production may play a regulatory role in brain injury following CO poisoning.