Induction of glucose transporter 1 expression through hypoxia-inducible factor 1α under hypoxic conditions in trophoblast-derived cells
Abstract
Glucose transporter 1 (GLUT1) plays an important role in the transport of glucose in the placenta. During early pregnancy, placentation occurs in a relatively hypoxic environment that is essential for appropriate embryonic development, and GLUT1 expression is enhanced in response to oxygen deficiency in the placenta. Hypoxia-inducible factor-1 (HIF-1)α is involved in the induction of GLUT1 expression in other cells. The present study was designed to test whether HIF-1α is involved in hypoxia-induced activation of GLUT1 expression using trophoblast-derived human BeWo and rat Rcho-1 cells as models. GLUT1 mRNA and protein expression were elevated under 5% O 2 or in the presense of cobalt chloride, which has been shown to mimic hypoxia. Using rat GLUT1 (rGLUT1) promoter–luciferase constructs, we showed that this up-regulation was mediated at the transcriptional level. Deletion mutant analysis of the rGLUT1 promoter indicated that a 184 bp hypoxia-responsive element (HRE) of the promoter was essential to increase GLUT1 reporter gene expression in response to low-oxygen conditions. BeWo and Rcho-1 cells cultured under 5% O 2 or with CoCl 2 showed increased expression of HIF-1α protein compared with those cultured under 20% O 2 . To test whether this factor is directly involved in hypoxia-induced GLUT1 promoter activation, BeWo and Rcho-1 cells were transiently transfected with an HIF-1α expression vector. Exogeneous HIF-1α markedly increased the GLUT1 promoter activity from constructs containing the HRE site, while the GLUT1 promoter constructs lacking the HRE site were not activated by exogenous HIF-1α These data demonstrate that GLUT1 is up-regulated under 5% O 2 or in the presence of CoCl 2 in the placental cell lines through HIF-1α interaction with a consensus HRE site of the GLUT1 promoter.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the human placenta in vitro, acute hypoxia leads to upregulated expression of GLUT1 and GLUT3.
“In the human placenta in vitro, acute hypoxia leads to upregulated expression of the GLUT1 and GLUT3 (178, 249).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [249]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Wang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5510 · Cited by 6,212 · see citing works
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535 · see citing works
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180 · see citing works
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · cited 2× · see citing works
“This mechanism accounts for HIF-1 stabilization in hypoxic cells, allowing nuclear translocation and dimerization with HIF-1 (Maxwell et al. 1999, Ivan et al. 2001, Jakkola et al. 2001).”
BackgroundActivation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
Forsythe, J. A., Jiang, B.-H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., & Semenza, G. L. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4604 · Cited by 3,981 · see citing works
Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333 · see citing works
Semenza, G. L., & Wang, G. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5447 · Cited by 2,617 · see citing works
A conserved family of prolyl-4-hydroxylases that modify HIF
Bruick, R. K., & McKnight, S. L. (2001) · Science · doi:10.1126/science.1066373 · Cited by 2,549 · see citing works
Huang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7987 · Cited by 2,113 · see citing works
Semenza, G. L., Jiang, B.-H., Leung, S. W., Passantino, R., Concordet, J.-P., Maire, P., & Giallongo, A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.51.32529 · Cited by 1,752 · see citing works
Sequence and Structure of a Human Glucose Transporter
Mueckler, M. M., Caruso, C., Baldwin, S. A., Panico, M., Blench, I., Morris, H. R., Allard, W. J., Lienhard, G. E., & Lodish, H. F. (1985) · Science · doi:10.1126/science.3839598 · Cited by 1,529 · see citing works
Huang, E. L., Arany, Z. P., Livingston, D. M., & Bunn, H. F. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.32253 · Cited by 1,190 · see citing works
(1996) · PubMed · Cited by 1,188 · see citing works
Oxygen sensing and molecular adaptation to hypoxia
Bunn, H. F., & Poyton, R. Ο. (1996) · Physiological Reviews · doi:10.1152/physrev.1996.76.3.839 · Cited by 1,185 · see citing works
Dimerization, DNA Binding, and Transactivation Properties of Hypoxia-inducible Factor 1
Jiang, B.-H., Rue, E., Wang, G. L., Roe, R., & Semenza, G. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.30.17771 · Cited by 1,106 · see citing works
Oncogenic alterations of metabolism
Dang, C. V., & Semenza, G. L. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01344-9 · Cited by 1,106 · see citing works
Semenza, G. L., & Wang, G. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5447-5454.1992 · Cited by 951 · see citing works
Regulation of Human Placental Development by Oxygen Tension
Genbačev, O., Zhou, Y., Ludlow, J. W., & Fisher, S. J. (1997) · Science · doi:10.1126/science.277.5332.1669 · Cited by 914 · see citing works
Regulation of glut1 mRNA by Hypoxia-inducible Factor-1
Chen, C., Pore, N., Behrooz, A., Ismail‐Beigi, F., & Maity, A. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010144200 · Cited by 768 · see citing works
Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy.
Rodesch, F., Simon, P., Donner, C., & Jauniaux, E. R. M. (1992) · PubMed · Cited by 753 · see citing works
Caniggia, I., Mostachfi, H., Winter, J., Gassmann, M., Lye, S. J., Kuliszewski, M., & Post, M. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8316 · Cited by 644 · see citing works
Genbačev, O., Joslin, R. J., Damsky, C. H., Polliotti, B., & Fisher, S. J. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118447 · Cited by 573 · see citing works
Firth, J. D., Ebert, B. L., Pugh, C. W., & Ratcliffe, P. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.14.6496 · Cited by 525 · see citing works
Adhesive and degradative properties of human placental cytotrophoblast cells in vitro.
Fisher, S. J., Cui, T. Y., Zhang, L., Hartman, L., Grahl, K., Zhang, G. Y., Tarpey, J., & Damsky, C. H. (1989) · The Journal of Cell Biology · doi:10.1083/jcb.109.2.891 · Cited by 465 · see citing works
Kallio, P. J., Pongratz, I., Gradin, K., McGuire, J., & Poellinger, L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.11.5667 · Cited by 415 · see citing works
Minchenko, О. H., Leshchinsky, I., Opentanova, I., Sang, N., Srinivas, V., Armstead, V. E., & Caro, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110978200 · Cited by 370 · see citing works
Jauniaux, E. R. M., Watson, A. L., & Burton, G. J. (2001) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2001.111935 · Cited by 316 · see citing works
Faria, T. N., & Soares, M. J. (1991) · Endocrinology · doi:10.1210/endo-129-6-2895 · Cited by 202 · see citing works
Wood, S. M., Wiesener, M. S., Yeates, K. M., Okada, N., Pugh, C. W., Maxwell, P. H., & Ratcliffe, P. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.14.8360 · Cited by 189 · see citing works
Behrooz, A., & Ismail‐Beigi, F. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.9.5555 · Cited by 167 · see citing works
Semenza, G. L. (1994) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(18)30134-5 · Cited by 133 · see citing works
Placental glucose transporter gene expression and metabolism in the rat.
Zhou, J., & Bondy, C. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116305 · Cited by 125 · see citing works
Ishida, H., Irie, K., Itoh, T., Furukawa, T., & Tokunaga, O. (1997) · Cancer · doi:10.1002/(sici)1097-0142(19970915)80:6 · Cited by 101 · see citing works
Quantitation and immunolocalization of glucose transporters in the human placenta
Barrosa, L. F., Yudilevich, D. L., Jarvis, S. M., Beaumont, N. J., & Baldwin, S. A. (1995) · Placenta · doi:10.1016/0143-4004(95)90031-4 · Cited by 100 · see citing works
The effect of hypoxia on human trophoblast in culture: Morphology, glucose transport and metabolism
Esterman, A., Greco, M. A., Mitani, Y., Finlay, T. H., Ismail-Beigi, F., & Dancis, J. (1997) · Placenta · doi:10.1016/s0143-4004(97)90084-9 · Cited by 95 · see citing works
Asano, T., Shibasaki, Y., Kasuga, M., et al. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(88)90268-9 · Cited by 85 · see citing works
Taylor, C. M., Stevens, H., Anthony, F. W., et al. (1997) · Placenta · doi:10.1016/s0143-4004(97)80047-1 · Cited by 82 · see citing works
RhoA/Rho-Kinase Cascade Is Involved in Oxytocin-Induced Rat Uterine Contraction
Tahara, M., Morishige, K., Sawada, K., et al. (2002) · Endocrinology · doi:10.1210/endo.143.3.8696 · Cited by 80 · see citing works
Self-citationSpeeg, K. V., Azizkhan, J. C., & Stromberg, K. (1976) · PubMed · Cited by 78 · see citing works
Zhou, Y., Chiu, K., Brescia, R. J., Combs, C. A., Katz, M. A., Kitzmiller, J. L., Heilbron, D. C., & Fisher, S. J. (1993) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(93)90172-f · Cited by 68 · see citing works
Establishment of a rat placental cell line expressing characteristics of extraembryonic membranes
Soares, M. J., Schaberg, K. D., Pinal, C. S., et al. (1987) · Developmental Biology · doi:10.1016/0012-1606(87)90466-0 · Cited by 64 · see citing works
Glycolysis and Gluconeogenesis
Berg, J. M., Tymoczko, J. L., & Stryer, L. (2002) · Cited by 63 · see citing works
Increase in human placental glucose transporter-1 during pregnancy
Sakata, M., Kurachi, H., Imai, T., Tadokoro, C., Yamaguchi, M., Yoshimoto, Y., Oka, Y., & Miyake, A. (1995) · European Journal of Endocrinology · doi:10.1530/eje.0.1320206 · Cited by 57 · see citing works
Self-citation8-bromo-cyclicAMP stimulates glucose transporter-1 expression in a human choriocarcinoma cell line
Ogura, K., Sakata, M., Okamoto, Y., et al. (2000) · Journal of Endocrinology · doi:10.1677/joe.0.1640171 · Cited by 56 · see citing works
Self-citationOgura, K., Sakata, M., Yamaguchi, M., Kurachi, H., & Murata, Y. (1999) · Journal of Endocrinology · doi:10.1677/joe.0.1600443 · Cited by 42 · see citing works
Self-citationDifferentiation-dependent expression of gelatinase B/matrix metalloproteinase-9 in trophoblast cells
Peters, T. J., Albieri, A., Bevilacqua, E. M. A. F., et al. (1999) · Cell and Tissue Research · doi:10.1007/s004410051235 · Cited by 35 · see citing works
Okamoto, Y., Sakata, M., Yamamoto, T., et al. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5860 · Cited by 16 · see citing works
Self-citation8-Bromo-cAMP inhibits glucose transport activity in mouse placental cells in culture
Sakata, M., Yamaguchi, M., Tasuku, I. M. A. I., Tadokoro, C., Yoshimoto, Y., Oka, Y., Kurachi, H., & Miyake, A. (1996) · Journal of Endocrinology · doi:10.1677/joe.0.1500319 · Cited by 14 · see citing works
Self-citationOxygen-dependent regulation of erythropoietin gene expression in rat hepatocytes
Göpfert, T., Eckardt, K., Geb, B., & Kurtz, A. (1997) · Kidney International · doi:10.1038/ki.1997.70 · Cited by 5 · see citing works
(1998) · Pure Amsterdam UMC · doi:10.1002/(sici)1097-0142(19980701)83:1 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Placental Origins of Chronic Disease
Burton, G. J., Fowden, A. L., & Thornburg, K. L. (2016) · Physiological Reviews · doi:10.1152/physrev.00029.2015 · Cited by 717 · see citing works
Wang, B., Wood, I. S., & Trayhurn, P. (2007) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-007-0301-8 · Cited by 392 · see citing works
Immunity, Hypoxia, and Metabolism–the Ménage à Trois of Cancer: Implications for Immunotherapy
Riera-Domingo, C., Audigé, A., Granja, S., Cheng, W.-C., Ho, P.-C., Baltazar, F., Stockmann, C., & Mazzone, M. (2020) · Physiological Reviews · doi:10.1152/physrev.00018.2019 · Cited by 310 · see citing works
Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy
Pringle, K. G., Kind, K. L., Sferruzzi-Perri, A. N., Thompson, J. G., & Roberts, C. T. (2010) · Human Reproduction Update · doi:10.1093/humupd/dmp046 · Cited by 259 · see citing works
Klabatsa, A., Sheaff, M. T., Steele, J. P. C., Evans, M. T., Rudd, R. M., & Fennell, D. A. (2006) · Lung Cancer · doi:10.1016/j.lungcan.2005.07.010 · Cited by 53 · see citing works
Adaptation of Human CD4+ T Cells to Pathophysiological Hypoxia: A Transcriptome Analysis
GABER, T., HÄUPL, T., SANDIG, G., TYKWINSKA, K., FANGRADT, M., TSCHIRSCHMANN, M., HAHNE, M., DZIURLA, R., EREKUL, K., LAUTENBACH, M., et al. (2009) · The Journal of Rheumatology · doi:10.3899/jrheum.090255 · Cited by 47 · see citing works
Tissot van Patot, M. C., Ebensperger, G., Gassmann, M., & Llanos, A. J. (2012) · High Altitude Medicine & Biology · doi:10.1089/ham.2012.1046 · Cited by 45 · see citing works
Hypoxic microenvironment in cancer: role in metabolic reprogramming
Sureka, N., Maheshwari, R., Agravat, A., Singhal, S., Zaman, S., Rishi, B., Siraj, F., Zaheer, S., & Misra, A. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1771365 · Cited by 11 · see citing works
- Authors
- Hayashi, M., Sakata, M., Takeda, T., Yamamoto, T., Okamoto, Y., Sawada, K., Kimura, A., Minekawa, R., Tahara, M., Tasaka, K., & Murata, Y.
- Affiliations
- The University of Osaka (JP)
- Osaka International Cancer Institute (JP)
- ORCID
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2004-10
- Volume
- 183
- Issue
- 1
- Pages
- 145-154
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2126592654
- Cited by
- 234
- References
- 51
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 14 · 2023: 21 · 2022: 9 · 2021: 28 · 2020: 21 · 2019: 6 · 2018: 16 · 2017: 20 · 2016: 12 · 2015: 9 · 2014: 4 · 2013: 7 · 2012: 10
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- glucose transporter 1, GLUT1, hypoxia-inducible factor-1α, hypoxia, trophoblast, placenta, hypoxia response element, transcriptional regulation, cobalt chloride, BeWo cells, glucose transport
- MeSH terms
- Hypoxia, Cobalt, Deoxyglucose, Female, Humans, Monosaccharide Transport Proteins, Oxygen, Pregnancy, RNA, Messenger, Transcription Factors, Trophoblasts, Immunoblotting, Blotting, Northern, Response Elements, Cell Line, Tumor, Glucose Transporter Type 1, Hypoxia-Inducible Factor 1, alpha Subunit
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
