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Am J Physiol Cell Physiol 284: C310-C315, 2003. First published September 25, 2002; doi:10.1152/ajpcell.00253.2002
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Vol. 284, Issue 2, C310-C315, February 2003

Hypoxia reduces expression and function of system A amino acid transporters in cultured term human trophoblasts

D. M. Nelson1, S. D. Smith1, T. C. Furesz2, Y. Sadovsky1,3, V. Ganapathy5, C. A. Parvin4, and C. H. Smith2

1 Department of Obstetrics and Gynecology, 2 Department of Pediatrics and St. Louis Children's Hospital, and Departments of 3 Cell Biology and Physiology and 4 Pathology, Washington University School of Medicine, St. Louis, Missouri 63110-1094; and 5 Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912-2100

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% O2 or in 1% and 3% O2 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% O2 and by 37% in 3% O2 (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% O2 and by 20% in 3% O2 (P < 0.05) compared with standard conditions at 72 h. Hypoxia (1% O2) 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.

placenta; differentiation; system ASC; system L


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