Effects of hypoxia on heme oxygenase expression in human chorionic villi explants and immortalized trophoblast cells

S. D. Appleton, G. S. Marks, K. Nakatsu, J. F. Brien, G. N. Smith, C. H. Graham, G. E. Lash
2003 American Journal of Physiology. Heart and Circulatory Physiology  
Although hypoxia induces heme oxygenase (HO)-1 protein and mRNA expression in many cell types, hypoxia has also been shown to decrease HO-1 mRNA and protein expression. We tested the hypothesis that 24-h preexposure to hypoxia in human placental preparations suppresses HO protein expression and enzymatic function. Immortalized HTR-8/SVneo first-trimester trophoblast cells and explants of normal human chorionic villi (CV) from term placentas were cultured for 24 h in 1%, 5%, or 20% O 2. HO
more » ... r 20% O 2. HO protein levels were determined by Western blot analysis, and microsomal HO activity was measured. HO-2 protein content was decreased by 17% and 5% in human trophoblast cells after 24-h exposure to 1% and 5% O 2, respectively, versus 20% O2. In contrast, HO-2 protein content in CV explants was unaffected by changes in oxygenation. HO-1 protein content, which was barely detectable in both biological systems, was not affected by changes in oxygenation. Similarly, HO enzymatic activity was unchanged in both preparations after 24-h exposure to 1%, 5%, or 20% O 2. The above data do not support the hypothesis that hypoxia in the human placenta suppresses both HO protein content and HO protein function. The present observations reinforce the necessity to determine both HO protein expression and function. heme oxygenase activity; heme oxygenase-1 expression; carbon monoxide; hypoxia; placenta HEME OXYGENASE (HO) catalyzes the breakdown of heme in the presence of oxygen (O 2 ) and NADPH to form carbon monoxide (CO), biliverdin, and iron. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Both biliverdin and bilirubin have been shown to be potent antioxidants in several tissues (30), and CO has been proposed to play a role in cell-cell communication and in the relaxation of blood vessels (19, (32) (33) (34) . Earlier studies on the stoichiometry of the HO reaction demonstrated that HO consumed 3
doi:10.1152/ajpheart.00655.2002 pmid:12578814 fatcat:thgaami5xvaj7nov7w566qwoke