Abstract
Increased oxidative stress (OS) is implicated in the pathophysiology of several pregnancy disorders. We aimed to investigate the effect of tert-butylhydroperoxide (TBHP)-induced OS upon the placental transport of the neutral amino acids l-methionine (l-Met) and l-alanine (l-Ala), by using a human trophoblast cell model (BeWo cells). TBHP reduced both total and Na+-independent 14C-l-Met intracellular steady-state accumulation over time (Amax), by reducing non-system l-mediated uptake – most probably system y+ – while having no effect on system L. Moreover, TBHP reduced total 14C-l-Ala Amax through an inhibition of system A. The effect of TBHP upon total, but not system A-mediated, 14C-l-Ala uptake was dependent upon phosphoinositide 3-kinase (PI3K) and protein kinase C (PKC) activation, and was completely prevented by the polyphenol quercetin. In conclusion, a reduction in placental uptake of neutral amino acids may contribute to the deleterious effects of pregnancy disorders associated with OS.
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