Vol. 282, Issue 6, H2055-H2059, June 2002
Heme oxygenase activity in placenta: direct dependence on
oxygen availability
Scott D.
Appleton1,
Gerald S.
Marks1,
Kanji
Nakatsu1,
James F.
Brien1,
Graeme N.
Smith1,2,3, and
Charles H.
Graham1,2
1 Departments of Pharmacology and Toxicology,
2 Anatomy and Cell Biology,
and 3 Obstetrics and Gynaecology, Queen's
University, Kingston, Ontario, Canada K7L 3N6
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 O2 for each molecule of CO formed from heme, and HO activity may be limited by O2 availability. To test
the hypothesis that low physiological O2 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% O2. Results revealed that HO
activity was directly dependent on O2 concentration. Thus,
although hypoxia may increase HO protein and mRNA expression, there is
a progressive decrease in HO activity with decreasing O2
concentration and the dependence of HO activity on O2
concentration is similar in chorionic villi from noninfarcted areas of
preeclamptic and normotensive placenta.
heme oxygenase-1 expression; carbon monoxide; hypoxia
