Nitric oxide and superoxide impair human placental amino acid uptake and increase Na+ permeability: implications for fetal growth.
Based on evidence that thiol and tyrosine reagents inhibit some amino acid transporters, we tested the hypothesis that NO- and O2- -derived free radicals would impair nutrient uptake by the human placenta. Syncytiotrophoblast microvillous plasma membrane vesicles (MVM) and placental villous fragments were exposed to the drug SIN-1 in the presence or absence of superoxide dismutase (SOD) and hemoglobin (Hb). The uptake of [3H]arginine, [3H]taurine, and [3H]leucine; [14C]MeAIB; and 22Na was studied in MVM, whereas the uptake of [3H]taurine was examined in villous fragments. Nitrotyrosine formation was assessed by Western blotting and quantified by ELISA. In MVM, SIN-1 caused an inhibition of [3H]arginine, [3H]taurine, and [14C]MeAIB uptake but had no significant effect on equilibrium [3H]leucine uptake. These effects were prevented by SOD or Hb, implying that both NO and O2- radicals were essential. In contrast, 22Na+ uptake was significantly increased, and this effect was prevented by SOD. In villous fragments, SIN-1 impaired Na+-dependent [3H]taurine uptake, with no effect on Na+-independent uptake. Increased nitrotyrosine formation was observed in MVM after SIN-1 treatment. Endogenous NO- and O2- -derived free radicals may alter human placental nutrient transfer in vivo, with implications for fetal growth.
Khullar
Sulekha
S
Academic Unit of Child Health, Manchester University, St. Mary's Hospital, Manchester M13 0JH, UK.
Greenwood
Susan L
SL
McCord
Nicola
N
Glazier
Jocelyn D
JD
Ayuk
Paul T-Y
PT
D000596:Amino Acids / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D008871:Microvilli / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010920:Placenta / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D012964:Sodium / Q000378:metabolism*; D013347:Subcellular Fractions / Q000737:chemistry / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014327:Trophoblasts / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D000596:Amino Acids; D005609:Free Radicals; D020030:Nitric Oxide Donors; D013481:Superoxides; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C002385:linsidomine; D012964:Sodium; D008981:Molsidomine