Time course of increased heme oxygenase activity and expression after experimental intracerebral hemorrhage: correlation with oxidative injury

Heme oxygenase (HO) activity in tissue adjacent to an intracerebral hematoma may modulate cellular vulnerability to heme-mediated oxidative injury. Although HO-1 is induced after experimental intracerebral hemorrhage (ICH), the time course of this induction, its effect on tissue HO activity, and its association with oxidative injury markers has not been defined. We therefore quantified HO activity, HO-1 expression, tissue heme content, and protein carbonylation for 8 days after injection of autologous blood into the mouse striatum. Increased striatal HO-1 protein was observed within 24 h, peaked on day 5 at a level that was 10-fold greater than baseline, and returned to baseline by day 8; HO-2 expression was not altered. HO activity increased by only 1.6-fold at its peak on day 5, and had also returned to baseline by day 8. A significant increase in protein carbonylation was observed at 3-5 days, which also was markedly attenuated by 8 days, concomitant with a return of tissue heme to near-normal levels. These results suggest that the increase in HO activity in tissue surrounding an experimental ICH is considerably less than would be predicted based on an analysis of HO-1 expression per se. As HO-1 expression is temporally associated with increased tissue heme and increased protein carbonylation, it may be more useful as a marker of heme-mediated oxidative stress in ICH models, rather than as an index of HO activity.