HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/C477    most recent 00075.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Baumann, M. U. Articles by Illsley, N. P. Search for Related Content PubMed PubMed Citation Articles by Baumann, M. U. Articles by Illsley, N. P.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Hypoxic upregulation of glucose transporters in BeWo choriocarcinoma cells is mediated by hypoxia-inducible factor-1

Department of Obstetrics, Gynecology, and Women's Health, New Jersey Medical School, Newark, New Jersey

Submitted 20 February 2007 ; accepted in final form 11 April 2007

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-1 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-1. 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.

glucose transporter 1; glucose transporter 3; glucose transport

This article has been cited by other articles:

				K.G. Pringle, K.L. Kind, A.N. Sferruzzi-Perri, J.G. Thompson, and C.T. Roberts Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy Hum. Reprod. Update, November 19, 2009; (2009) dmp046v1. [Abstract] [Full Text] [PDF]

				J. R. Araujo, P. Goncalves, and F. Martel Modulation of Glucose Uptake in a Human Choriocarcinoma Cell Line (BeWo) by Dietary Bioactive Compounds and Drugs of Abuse J. Biochem., August 1, 2008; 144(2): 177 - 186. [Abstract] [Full Text] [PDF]

				I. A. Simpson, D. Dwyer, D. Malide, K. H. Moley, A. Travis, and S. J. Vannucci The facilitative glucose transporter GLUT3: 20 years of distinction Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E242 - E253. [Abstract] [Full Text] [PDF]

				D. Sikder and T. Kodadek The neurohormone orexin stimulates hypoxia-inducible factor-1 activity Genes & Dev., November 15, 2007; 21(22): 2995 - 3005. [Abstract] [Full Text] [PDF]