Subscribe to RSS
DOI: 10.1055/s-0029-1241862
© Georg Thieme Verlag KG Stuttgart · New York
COUP-TFII is Regulated by High Glucose in Endothelial Cells
Publication History
received 29.01.2009
accepted after second revision 17.09.2009
Publication Date:
27 October 2009 (online)
![](https://www.thieme-connect.de/media/hmr/201002/lookinside/thumbnails/10.1055-s-0029-1241862-1.jpg)
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
- 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
- 3 Gerszten RE, Wang TJ. The search for new cardiovascular biomarkers. Nature. 2008; 451 949-952
- 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
- 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
- 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
- 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
- 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
- 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
- 10 Khan AH, Pessin JE. Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways. Diabetologia. 2002; 45 1475-1483
- 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
- 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
- 13 Stenina OI. Regulation of vascular genes by glucose. Curr Pharm Des. 2005; 11 2367-2381
- 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
- 15 Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol. 2000; 132 365-386
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
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