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Horm Metab Res 2010; 42(2): 81-87
DOI: 10.1055/s-0029-1241862
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

COUP-TFII is Regulated by High Glucose in Endothelial Cells

C. Brunssen1 , S. Korten1 , M. Brux1 , S. Seifert2 , J. Roesler3 , S. R. Bornstein4 , H. Morawietz1 , W. Goettsch1
  • 1Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
  • 2Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
  • 3Department of Pediatrics, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
  • 4Department of Medicine III, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
Further Information

Publication History

received 29.01.2009

accepted after second revision 17.09.2009

Publication Date:
27 October 2009 (online)

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Abstract

Diabetes mellitus is an important risk factor for cardiovascular diseases. Clinical evidence supports a link between hyperglycemia, endothelial dysfunction, and vascular disorders. However, the precise molecular mechanisms causing endothelial dysfunction in diabetic patients remain unclear. An interesting novel mediator could be chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), which plays an essential role in glucose metabolism. COUP-TFII is known to be expressed in venous endothelial cells. In this study, we show COUP-TFII expression in human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells. HUVECs express glucose transporters 1, 3, 6, and 10, and the insulin receptor. Insulin in combination with glucose activates protein kinase B (PKB or Akt) phosphorylation via phosphoinositide 3-kinase (PI3-kinase). Short-term (60–240 min) stimulation of HUVECs with high glucose increased COUP-TFII expression independent of insulin. Long-term (48 h) stimulation of HUVECs with high glucose augmented expression of the insulin receptor and E-selectin, but downregulated COUP-TFII protein expression. Downregulation of COUP-TFII by shRNA leads to downregulation of E-selectin and upregulation of eNOS and glucose transporters. Our data suggest that COUP-TFII is regulated by glucose in a time- and dose-dependent manner in endothelial cells. COUP-TFII might affect endothelial function in a diabetic background.

Key words

chicken ovalbumin upstream promoter-transcription factor II - HUVEC - HCAEC - glucose transporter

References

  • 1 Milicevic Z, Raz I, Beattie SD, Campaigne BN, Sarwat S, Gromniak E, Kowalska I, Galic E, Tan M, Hanefeld M. Natural history of cardiovascular disease in patients with diabetes: Role of hyperglycemia.  Diabetes Care. 2008;  31 ((Suppl 2)) S155-S160
    Google Scholar
  • 2 Rask-Madsen C, King GL. Mechanisms of Disease: Endothelial dysfunction in insulin resistance and diabetes.  Nat Clin Pract Endocrinol Metab. 2007;  3 46-56
    Google Scholar
  • 3 Gerszten RE, Wang TJ. The search for new cardiovascular biomarkers.  Nature. 2008;  451 949-952
    Google Scholar
  • 4 Li L, Xie X, Qin J, Jeha GS, Saha PK, Yan J, Haueter CM, Chan L, Tsai SY, Tsai MJ. The nuclear orphan receptor COUP-TFII plays an essential role in adipogenesis, glucose homeostasis, and energy metabolism.  Cell Metab. 2009;  9 77-87
    Google Scholar
  • 5 Park JI, Tsai SY, Tsai MJ. Molecular mechanism of chicken ovalbumin upstream promoter-transcription factor (COUP-TF) actions.  Keio J Med. 2003;  52 174-181
    Google Scholar
  • 6 De Martino MU, Alesci S, Chrousos GP, Kino T. Interaction of the glucocorticoid receptor and the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII): implications for the actions of glucocorticoids on glucose, lipoprotein, and xenobiotic metabolism.  Ann N Y Acad Sci. 2004;  1024 72-85
    Google Scholar
  • 7 Hwung YP, Crowe DT, Wang LH, Tsai SY, Tsai MJ. The COUP transcription factor binds to an upstream promoter element of the rat insulin II gene.  Mol Cell Biol. 1988;  8 2070-2077
    Google Scholar
  • 8 Lou DQ, Tannour M, Selig L, Thomas D, Kahn A, Vasseur-Cognet M. Chicken ovalbumin upstream promoter-transcription factor II, a new partner of the glucose response element of the L-type pyruvate kinase gene, acts as an inhibitor of the glucose response.  J Biol Chem. 1999;  274 28385-28394
    Google Scholar
  • 9 Gosmanov AR, Stentz FB, Kitabchi AE. De novo emergence of insulin-stimulated glucose uptake in human aortic endothelial cells incubated with high glucose.  Am J Physiol Endocrinol Metab. 2006;  290 E516-E522
    Google Scholar
  • 10 Khan AH, Pessin JE. Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways.  Diabetologia. 2002;  45 1475-1483
    Google Scholar
  • 11 Artwohl M, Brunmair B, Furnsinn C, Holzenbein T, Rainer G, Freudenthaler A, Porod EM, Huttary N, Baumgartner-Parzer SM. Insulin does not regulate glucose transport and metabolism in human endothelium.  Eur J Clin Invest. 2007;  37 643-650
    Google Scholar
  • 12 Munzel D, Lehle K, Haubner F, Schmid C, Birnbaum DE, Preuner JG. Impact of diabetic serum on endothelial cells: An in-vitro-analysis of endothelial dysfunction in diabetes mellitus type 2.  Biochem Biophys Res Commun. 2007;  362 238-244
    Google Scholar
  • 13 Stenina OI. Regulation of vascular genes by glucose.  Curr Pharm Des. 2005;  11 2367-2381
    Google Scholar
  • 14 Catar RA, Muller G, Heidler J, Schmitz G, Bornstein SR, Morawietz H. Low-density lipoproteins induce the renin-angiotensin system and their receptors in human endothelial cells.  Horm Metab Res. 2007;  39 801-805
    Google Scholar
  • 15 Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers.  Methods Mol Biol. 2000;  132 365-386
    Google Scholar
  • 16 You LR, Lin FJ, Lee CT, DeMayo FJ, Tsai MJ, Tsai SY. Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity.  Nature. 2005;  435 98-104
    Google Scholar
  • 17 Wiernsperger NF. Is non-insulin dependent glucose uptake a therapeutic alternative? Part 2: Do such mechanisms fulfil the required combination of power and tolerability?.  Diabetes Metab. 2005;  31 521-525
    Google Scholar
  • 18 Hauguel-de Mouzon S, Challier JC, Kacemi A, Cauzac M, Malek A, Girard J. The GLUT3 glucose transporter isoform is differentially expressed within human placental cell types.  J Clin Endocrinol Metab. 1997;  82 2689-2694
    Google Scholar
  • 19 Park JL, Loberg RD, Duquaine D, Zhang H, Deo BK, Ardanaz N, Coyle J, Atkins KB, Schin M, Charron MJ, Kumagai AK, Pagano PJ, Brosius  FC. GLUT4 facilitative glucose transporter specifically and differentially contributes to agonist-induced vascular reactivity in mouse aorta.  Arterioscler Thromb Vasc Biol. 2005;  25 1596-1602
    Google Scholar
  • 20 Mann GE, Yudilevich DL, Sobrevia L. Regulation of amino acid and glucose transporters in endothelial and smooth muscle cells.  Physiol Rev. 2003;  83 183-252
    Google Scholar
  • 21 Chisalita SI, Arnqvist HJ. Insulin-like growth factor I receptors are more abundant than insulin receptors in human micro- and macrovascular endothelial cells.  Am J Physiol Endocrinol Metab. 2004;  286 E896-E901
    Google Scholar
  • 22 Andreozzi F, Formoso G, Prudente S, Hribal ML, Pandolfi A, Bellacchio E, Di Silvestre S, Trischitta V, Consoli A, Sesti G. TRIB3 R84 variant is associated with impaired insulin-mediated nitric oxide production in human endothelial cells.  Arterioscler Thromb Vasc Biol. 2008;  28 1355-1360
    Google Scholar
  • 23 Perilhou A, Tourrel-Cuzin C, Kharroubi I, Henique C, Fauveau V, Kitamura T, Magnan C, Postic C, Prip-Buus C, Vasseur-Cognet M. The transcription factor COUP-TFII is negatively regulated by insulin and glucose via Foxo1- and ChREBP-controlled pathways.  Mol Cell Biol. 2008;  28 6568-6579
    Google Scholar
  • 24 Bellin C, de Wiza DH, Wiernsperger NF, Rosen P. Generation of reactive oxygen species by endothelial and smooth muscle cells: influence of hyperglycemia and metformin.  Horm Metab Res. 2006;  38 732-739
    Google Scholar
  • 25 Knoch KP, Bergert H, Borgonovo B, Saeger HD, Altkruger A, Verkade P, Solimena M. Polypyrimidine tract-binding protein promotes insulin secretory granule biogenesis.  Nat Cell Biol. 2004;  6 207-214
    Google Scholar
  • 26 Kado S, Wakatsuki T, Yamamoto M, Nagata N. Expression of intercellular adhesion molecule-1 induced by high glucose concentrations in human aortic endothelial cells.  Life Sci. 2001;  68 727-737
    Google Scholar
  • 27 Piconi L, Quagliaro L, Da Ros R, Assaloni R, Giugliano D, Esposito K, Szabo C, Ceriello A. Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly(ADP-ribose) polymerase.  J Thromb Haemost. 2004;  2 1453-1459
    Google Scholar
  • 28 Bardoux P, Zhang P, Flamez D, Perilhou A, Lavin TA, Tanti JF, Hellemans K, Gomas E, Godard C, Andreelli F, Buccheri MA, Kahn A, Le Marchand-Brustel Y, Burcelin R, Schuit F, Vasseur-Cognet M. Essential role of chicken ovalbumin upstream promoter-transcription factor II in insulin secretion and insulin sensitivity revealed by conditional gene knockout.  Diabetes. 2005;  54 1357-1363
    Google Scholar

Correspondence

W. Goettsch

University Hospital Carl Gustav Carus

Dresden University of Technology

Fetscherstraße 74

01307 Dresden

Germany

Phone: +49/351/458 6677

Fax: +49/351/ 458 6354

Email: winfried.goettsch@tu-dresden.de