Hypoxia reduces expression and function of system A amino acid transporters in cultured term human trophoblasts.
We tested the hypothesis that hypoxia diminishes the expression and transport of neutral amino acids by system A in full-term human trophoblasts. Cytotrophoblasts from normal human placentas were cultured in standard conditions of 20% O(2) or in 1% and 3% O(2) for 24 h before assay. Neutral amino acid transport for systems A, ASC, and L was assayed at 24 and 72 h by the cluster-tray technique. Hypoxia during the initial 24 h of culture reduced system A transport by 82% in 1% O(2) and by 37% in 3% O(2) (P < 0.01) compared with standard conditions. Hypoxia during the latter 24 h of the 72 h in culture reduced system A transport by 55% in 1% O(2) and by 20% in 3% O(2) (P < 0.05) compared with standard conditions at 72 h. Hypoxia (1% O(2)) also reduced total amino acid transport by 40% in the more differentiated syncytiotrophoblasts present at 72 h. Northern analysis of trophoblasts in standard conditions showed that subtypes of human amino acid transporter A (hATA1 and hATA2) were each expressed in cytotrophoblasts and syncytiotrophoblasts. Hypoxia decreased expression of hATA1 and hATA2 in both trophoblast phenotypes. We conclude that hypoxia downregulates system A transporter expression and activity in cultured human trophoblasts.
Nelson
D M
DM
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110-1094, USA. nelsondm@msnotes.wustl.edu
Smith
S D
SD
Furesz
T C
TC
Sadovsky
Y
Y
Ganapathy
V
V
Parvin
C A
CA
Smith
C H
CH
D026924:Amino Acid Transport System A / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism* / Q000503:physiopathology; D005311:Fetal Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D010922:Placenta Diseases / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*
D026924:Amino Acid Transport System A; C445761:SLC38A1 protein, human