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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Baumann, Marc U. Zamudio, Stacy Illsley, Nicholas P. |
| Description | Country affiliation: United States Author Affiliation: Baumann MU ( Dept. of Obstetrics, Gynecology, and Women's Health, New Jersey Medical School, 185 S. Orange Ave., MSB E506, Newark, NJ 07103, USA.) |
| Abstract | Placental hypoxia has been implicated in pregnancy pathologies, including fetal growth restriction and preeclampsia; however, the mechanism by which the trophoblast cell responds to hypoxia has not been adequately explored. Glucose transport, a process crucial to fetoplacental growth, is upregulated by hypoxia in a number of cell types. We investigated the effects of hypoxia on the regulation of trophoblast glucose transporter (GLUT) expression and activity in BeWo choriocarcinoma cells, a trophoblast cell model, and human placental villous tissue explants. GLUT1 expression in BeWo cells was upregulated by the hypoxia-inducing chemical agents desferroxamine and cobalt chloride. Reductions in oxygen tension resulted in dose-dependent increases in GLUT1 and GLUT3 expression. Exposure of cells to hypoxic conditions also resulted in an increase in transepithelial glucose transport. A role for hypoxia-inducible factor (HIF)-1 was suggested by the increase in HIF-1alpha as a result of hypoxia and by the increase in GLUT1 expression following treatment of BeWo with MG-132, a proteasomal inhibitor that increases HIF-1 levels. The function of HIF-1 was confirmed in experiments where the hypoxic upregulation of GLUT1 and GLUT3 was inhibited by antisense HIF-1alpha. In contrast to BeWo cells, hypoxia produced minimal increases in GLUT1 expression in explants; however, treatment with MG-132 did upregulate syncytial basal membrane GLUT1. Our results show that GLUTs are upregulated by hypoxia via a HIF-1-mediated pathway in trophoblast cells and suggest that the GLUT response to hypoxia in vivo will be determined not only by low oxygen tension but also by other factors that modulate HIF-1 levels. |
| File Format | HTM / HTML |
| ISSN | 03636143 |
| e-ISSN | 15221563 |
| Journal | American Journal of Physiology - Cell Physiology |
| Issue Number | 1 |
| Volume Number | 293 |
| Language | English |
| Publisher | American Physiological Society |
| Publisher Date | 2007-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Cell Biology Cell Hypoxia Choriocarcinoma Metabolism Chorionic Villi Glucose Transporter Type 1 Glucose Transporter Type 3 Glucose Hypoxia-inducible Factor 1, Alpha Subunit Trophoblasts Actins Drug Effects Cell Line, Tumor Pathology Physiopathology Cobalt Pharmacology Cysteine Proteinase Inhibitors Deferoxamine Dose-response Relationship, Drug Genetics Leupeptins Oligonucleotides, Antisense Pregnancy Proteasome Endopeptidase Complex Receptors, Transferrin Time Factors Tissue Culture Techniques Up-regulation Research Support, N.i.h., Extramural |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Physiology |
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