Epidermal growth factor and sphingosine-1-phosphate stimulate Na+/H+exchanger activity in the human placental syncytiotrophoblast
Open Access
- 1 December 2007
- journal article
- Published by American Physiological Society in American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Vol. 293 (6), R2290-R2294
- https://doi.org/10.1152/ajpregu.00328.2007
Abstract
The Na+/H+ exchanger (NHE) has a key role in intracellular pH ([pH]i) regulation of the syncytiotrophoblast in the human placenta and may have a role in the life cycle of this cell. In other cells the NHE (actually a family of up to 9 isoforms) is regulated by a variety of factors, but its regulation in the syncytiotrophoblast has not been studied. Here, we tested the hypotheses that EGF and sphingosine-1-phosphate (S1P), both of which affect trophoblast apoptosis and, in other cell types, NHE activity, stimulate syncytiotrophoblast NHE activity. Villous fragments from term human placentas were loaded with the pH-sensitive dye, BCECF. NHE activity was measured by following the recovery of syncytiotrophoblast [pH]i following an imposed acid load, in the presence and absence of EGF, S1P, and specific inhibitors of NHE activity. Both EGF and S1P caused a dose-dependent upregulation of NHE activity in the syncytiotrophoblast. These effects were blocked by amiloride 500 μM (a nonspecific NHE blocker) and HOE694 100 μM (NHE blocker with NHE1 and 2 isoform selectivity). Effects of EGF were also reduced by the NHE3 selective blocker S3226 (used at 1 μM). These data provide the first evidence that both EGF and S1P stimulate NHE activity in the syncytiotrophoblast; they appear to do so predominantly by activating the NHE1 isoform.Keywords
This publication has 44 references indexed in Scilit:
- Intracellular pH homeostasis in cultured human placental syncytiotrophoblast cells: recovery from acidificationAmerican Journal of Physiology-Cell Physiology, 2005
- Gestational profile of Na+/H+ exchanger and Cl−/HCO3− anion exchanger mRNA expression in placenta using real-time QPCRPlacenta, 2005
- Sphingosine-1-phosphate: an enigmatic signalling lipidNature Reviews Molecular Cell Biology, 2003
- G Protein PathwaysScience, 2002
- Regulation of Placental Transfer: The Na+/H+ Exchanger—A ReviewPlacenta, 2002
- Expression of the mRNAs and Proteins for the Na+/H+ Exchangers and Their Regulatory Factors in Baboon and Human Placental SyncytiotrophoblastEndocrinology, 2001
- Epidermal Growth Factor Regulation of Equine Glycoprotein Hormone α Subunit Expression in Trophoblast Cells1Biology of Reproduction, 2001
- p90RSK Is a Serum-stimulated Na+/H+ Exchanger Isoform-1 KinasePublished by Elsevier BV ,1999
- Epidermal growth factor in urine of pregnant women and in amniotic fluid throughout pregnancyGynecological Endocrinology, 1990
- Intracellular pH measurements in Ehrlich ascites tumor cells utilizing spectroscopic probes generated in situBiochemistry, 1979