Nitric oxide and superoxide impair human placental amino acid uptake and increase Na + permeability: implications for fetal growth

Abstract

Based on evidence that thiol and tyrosine reagents inhibit some amino acid transporters, we tested the hypothesis that NO- and O 2 −-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 O 2 − 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 O 2 −-derived free radicals may alter human placental nutrient transfer in vivo, with implications for fetal growth.