title: Effects of low oxygen levels on the expression and function of transporter OCTN2 in BeWo cells.
abstract: Although hypoxia is normal in early pregnancy, low placental oxygen concentrations later in pregnancy are often linked to complications such as pre-eclampsia and intrauterine growth restriction. The effects of low oxygen levels on drug and nutrient uptake via the organic cation transporter OCTN2 has been studied in BeWo cells, an in-vitro model of human trophoblast. BeWo cells were cultured under 20% (control) or 2% O(2) (hypoxia) for 48 h before each experiment. In-vitro hypoxia was also simulated by the addition of CoCl(2) to the cell culture medium. RT-PCR indicated increased transcription of OCTN2 in BeWo cells cultured under hypoxia, but Western blots did not show a corresponding increase in the amount of OCTN2 protein in the hypoxic cells compared with control. Hypoxia resulted in significant reductions in OCTN2-mediated carnitine uptake. Decreased placental transport of carnitine may lead to symptoms of carnitine deficiency in infants from hypoxic pregnancies, whether caused by high altitude, pre-eclampsia or other factors. The OCTN1 substrate ergothioneine reversed the effects of hypoxia on carnitine transport, but identical concentrations of N-acetylcysteine, another water-soluble intracellular antioxidant, did not have the same effect.
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Rytting
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Audus
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001692:Biological Transport; D015153:Blotting, Western; D002331:Carnitine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015687:Cell Hypoxia; D002822:Choriocarcinoma; D004305:Dose-Response Relationship, Drug; D004880:Ergothioneine / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074058:Solute Carrier Family 22 Member 5; D014158:Transcription, Genetic; D014327:Trophoblasts / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D004880:Ergothioneine; D002331:Carnitine; D000111:Acetylcysteine