Oxidative stress decreases uptake of neutral amino acids in a human placental cell line (BeWo cells)

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 (14)C-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 (14)C-L-Ala Amax through an inhibition of system A. The effect of TBHP upon total, but not system A-mediated, (14)C-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.

Keywords: 2-amino-2-norbornanecarboxylic acid; A(max); BCH; EGCG; LAT; MeAIB; N-ethylmaleimide; NEM; Na(+)-coupled neutral amino acid transporter; Nutrients; OS; Oxidative stress; Placenta; SNAT; STB; TBHP; Transport; accumulation at steady state; epigallocatechin-3-gallate; k(in); k(out); l-type amino acid transporter; oxidative stress; rate constant for inward transport; rate constant for outward transport; syncytiotrophoblast; tert-butylhydroperoxide; α-(methylamino)isobutyric acid.