Heme oxygenase expression in cultured human trophoblast cells during in vitro differentiation: effects of hypoxia.
Heme oxygenases (HO-1 and HO-2) are responsible for the production of carbon monoxide, a vasodilator. HO is important in controlling placental blood flow and expression can be sensitive to oxygen. We previously reported a reduction in HO-2 expression in placentae obtained from patients with pre-eclampsia or living at high altitude, both associated with placental hypoxia. Thus we hypothesized that HO expression in cultured trophoblasts would be altered by exposure to hypoxia. HO-1 and HO-2 expression was assessed in trophoblast cell cultures following exposure to different oxygen environments. Western blot analyses showed that HO-1 expression in syncytiotrophoblast was significantly lower than in cytotrophoblasts in standard conditions (p < 0.05). There was no difference in HO-1 expression in cytotrophoblasts transferred to 2% O2 for various times. However, exposure of syncytiotrophoblast cultures to hypoxia for 12 h resulted in a significant reduction in HO-1 expression (p < 0.05). HO-2 expression was not affected by exposure to hypoxia in either cytotrophoblast or syncytiotrophoblast cultures. Possible interpretations of these findings are that chronic hypoxia alone is not responsible for reduced HO-2 expression or a much longer exposure to chronic hypoxia (perhaps months) is required. This study also reinforces the complexities of HO regulation by oxygen.
Newby
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D
Maternal and Fetal Medicine Section, Institute of Medical Genetics, Yorkhill, Glasgow G3 8SJ, UK.
Cousins
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F
Myatt
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Lyall
F
F
D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D018053:Arsenites / Q000633:toxicity; D015153:Blotting, Western; D019256:Cadmium Chloride / Q000633:toxicity; D002454:Cell Differentiation; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D008298:Maleates / Q000633:toxicity; D008565:Membrane Proteins; D010100:Oxygen / Q000032:analysis / Q000494:pharmacology; D011247:Pregnancy; D017670:Sodium Compounds / Q000633:toxicity; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
D018053:Arsenites; D006063:Chorionic Gonadotropin; D008298:Maleates; D008565:Membrane Proteins; D017670:Sodium Compounds; C017947:sodium arsenite; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D000469:Alkaline Phosphatase; C014476:diethyl maleate; D019256:Cadmium Chloride; D010100:Oxygen