Heme oxygenase activity in placenta: direct dependence on oxygen availability

Carbon monoxide (CO), which is formed endogenously from heme catalyzed by heme oxygenase (HO), is proposed to play a role in vascular control. The mRNA and protein expression of the inducible isoform of HO (HO-1) increases in response to hypoxia, and it has been assumed that HO activity also increases. This assumption requires evaluation because the catalytic activity of HO requires three molecules of O-2 for each molecule of CO formed from heme, and HO activity may be limited by O-2 availability. To test the hypothesis that low physiological O-2 concentrations limit HO activity, heme-derived CO formation by microsomal fractions of homogenates of chorionic villi of human placentas was determined after exposure to 0, 1, 5, or 21% O-2. Results revealed that HO activity was directly dependent on O-2 concentration. Thus, although hypoxia may increase HO protein and mRNA expression, there is a progressive decrease in HO activity with decreasing O-2 concentration and the dependence of HO activity on O-2 concentration is similar in chorionic villi from noninfarcted areas of preeclamptic and normotensive placenta.