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

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 40; pp. 76 - 81
• Main Authors: Araújo, João Ricardo, Correia-Branco, Ana, Pereira, Ana Cláudia, Pinho, Maria João, Keating, Elisa, Martel, Fátima
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2013
• Subjects: Alanine - metabolism; Amino Acids, Neutral - metabolism; Cell Line; Female; Humans; Nutrients; Oxidative Stress; Phosphatidylinositol 3-Kinases - metabolism; Placenta; Placenta - cytology; Placenta - metabolism; Pregnancy; Protein Kinase C - metabolism; Quercetin - pharmacology; tert-Butylhydroperoxide - toxicity; Transport; STB; Oxidative stress; OS; BCH; EGCG; SNAT; MeAIB; kin; kout; TBHP; Placenta; NEM; Nutrients; Amax; Transport; LAT; N-ethylmaleimide; α-(methylamino)isobutyric acid; tert-butylhydroperoxide; k(out); Na(+)-coupled neutral amino acid transporter; l-type amino acid transporter; k(in); 2-amino-2-norbornanecarboxylic acid; rate constant for outward transport; A(max); syncytiotrophoblast; rate constant for inward transport; accumulation at steady state; epigallocatechin-3-gallate
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2013.06.073

•Oxidative stress is implicated in the pathophysiology of several pregnancy disorders.•We studied the effect of oxidative stress upon neutral amino acids placental uptake.•Placental uptake of l-methionine mediated by system y+ was decreased.•Placental uptake of l-alanine mediated by system A was also decreased.•Increased oxidative stress may have deleterious implications for fetal growth. 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.