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Am J Physiol Cell Physiol (September 25, 2002). doi:10.1152/ajpcell.00253.2002
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Articles in PresS, published online ahead of print September 25, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00253.2002
Submitted on May 31, 2002
Accepted on September 20, 2002

Hypoxia Reduces the Expression and Function of System A Amino Acid Transporters in Cultured Term Human Trophoblasts

D M Nelson1*, T C Furesz2, V Ganapathy3, C A Parvin4, Vadivel Ganapathy1, Curtis A Parvin1, and Carl H Smith1

1 Obstetrics and Gynecology, Washington University School of Medicine, St.Louis, MO, USA
2 Pediatrics and St. Louis Children's Hospital, Washington University School of Medicine, St.Louis, MO, USA
3 Biochemistry & Molecular Biology, Medical College of Georgia, Augusta, GA, USA
4 Cell Biology and Physiology, Washington University School of Medicine, St.Louis, MO, USA

* To whom correspondence should be addressed. E-mail: nelsondm{at}msnotes.wustl.edu.

We tested the hypothesis that hypoxia diminishes the expression and transport of neutral amino acids by system A in term human trophoblasts. Cytotrophoblasts from normal human placentas were cultured in standard conditions of 20% oxygen, or in 1% and 3% oxygen for the 24 h prior to assay. Neutral amino acid transport for systems A, ASC, and L was assayed at 24 h and 72 h by the cluster tray technique. Hypoxia during the initial 24 h of culture reduced system A transport by 82% in 1% oxygen and 37% in 3% oxygen (P< 0.01), compared to standard conditions. Hypoxia during the latter 24 h of the 72 h in culture reduced system A transport by 55% in 1% oxygen and by 20% in 3% oxygen (p< 0.05), compared to standard conditions at 72 h. Hypoxia (1% oxygen) also reduced total amino acid transport by 40% in the more differentiated syncytiotrophoblasts present at 72 h. Northern analysis of trophoblast in standard conditions showed that hATA 1 and hATA 2 were each expressed in cytotrophoblasts and syncytiotrophoblasts. Hypoxia decreased the expression of hATA 1 and hATA 2 in both of the trophoblast phenotypes. We conclude that hypoxia down regulates system A transporter expression and activity in cultured human trophoblasts.




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