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.
Appleton
Scott D
SD
Department of Pharmacology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Marks
Gerald S
GS
Nakatsu
Kanji
K
Brien
James F
JF
Smith
Graeme N
GN
Graham
Charles H
CH
D002248:Carbon Monoxide / Q000378:metabolism; D002824:Chorionic Villi / Q000201:enzymology / Q000648:ultrastructure; D005260:Female; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D000860:Hypoxia / Q000201:enzymology; D008565:Membrane Proteins; D008861:Microsomes / Q000201:enzymology; D010100:Oxygen / Q000008:administration & dosage*; D010920:Placenta / Q000201:enzymology*; D011225:Pre-Eclampsia / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D012044:Regression Analysis
D008565:Membrane Proteins; D012333:RNA, Messenger; D006418:Heme; D002248:Carbon Monoxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D010100:Oxygen