Effects of low oxygen levels on the expression and function of transporter OCTN2 in BeWo cells.
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.
Rytting
Erik
E
Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA.
Audus
Kenneth L
KL
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
D000975:Antioxidants; D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D004880:Ergothioneine; D002331:Carnitine; D000111:Acetylcysteine