Sp1 sites mediate activation of the plasminogen activator inhibitor-1 promoter by glucose in vascular smooth muscle cells.

The Journal of Biological Chemistry
Y Q ChenD E Vaughan

Abstract

This study was designed to characterize the direct effects of hyperglycemia on plasminogen activator inhibitor-1 (PAI-1) expression in cultured vascular smooth muscle cells. Glucose induced dose- and time-dependent increases of PAI-1 mRNA expression in rat aortic smooth muscle (RASM) cells in vitro. Using a series of luciferase reporter gene constructs containing PAI-1 5'-flanking sequence (from -6.4 kilobase to -42 base pairs (bp)) transfected into RASM, we found that glucose (25 mM) consistently induced a 4-fold increase in luciferase activity, with the response localized to sequence between -85 and -42 bp. Mutagenesis of two putative Sp1-binding sites located in the region of interest essentially obliterated the glucose-response. Electrophoretic mobility shift assays with radiolabeled oligonucleotides containing the two putative Sp1-binding sites from PAI-1 promoter and nuclear extracts from RASM cells revealed that glucose treatment markedly changed the mobility pattern of the major protein-DNA complexes. Supershift assay showed that transcription factor Sp1 was present in the complexes under control and hyperglycemic conditions. These results suggest that glucose regulates PAI-1 gene expression in RASM cells through an eff...Continue Reading

References

Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J SchneidermanD J Loskutoff
Sep 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·D A McClainJ E Kudlow
Jun 1, 1992·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·E L Bierman
Oct 1, 1989·Current Opinion in Cell Biology·C M Alexander, Z Werb
May 1, 1983·Journal of Cellular Physiology·P Libby, K V O'Brien
Oct 6, 1995·The Journal of Biological Chemistry·H C Towle
Nov 1, 1995·The Journal of Clinical Investigation·D M KerinsD E Vaughan
Jun 1, 1994·Molecular and Cellular Biology·M S German, J Wang
Aug 1, 1993·Metabolism: Clinical and Experimental·B J Potter van LoonA E Meinders
Sep 30, 1993·The New England Journal of Medicine·UNKNOWN Diabetes Control and Complications Trial Research GroupC Siebert
Jan 19, 1996·The Journal of Biological Chemistry·S Daniel, K H Kim
Apr 1, 1996·Arteriosclerosis, Thrombosis, and Vascular Biology·L A RobbieB Bennett
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·Q XiaoJ L Degen

❮ Previous
Next ❯

Citations

Mar 23, 2005·Current Opinion in Pharmacology·Bart De TaeyeDouglas E Vaughan
May 10, 2003·Journal of Molecular and Cellular Cardiology·John A SchoenhardDouglas E Vaughan
Dec 31, 2002·Journal of Diabetes and Its Complications·Sunao AsaumiSeijiro Mori
Mar 27, 2009·Nature Reviews. Nephrology·Hunjoo HaHi B Lee
Jun 15, 2000·The New England Journal of Medicine·H P Kohler, P J Grant
Jul 10, 2004·Antioxidants & Redox Signaling·Elitsa Y DimovaThomas Kietzmann
Nov 6, 2007·Antioxidants & Redox Signaling·Rui-Ming Liu
Oct 24, 2000·Kidney International·J P RerolleE P Rondeau
Mar 23, 2005·Kidney International·Susanne B NicholasWilla A Hsueh
Feb 15, 2005·International Journal of Clinical Practice·M Agirbasli
Jun 1, 2010·Journal of Diabetes Investigation·Munehiro KitadaGeorge L King
Apr 11, 2000·Molecular and Cellular Biology·P K Datta, H L Moses
Nov 30, 2005·Molecular and Cellular Biology·Gilles BuchwalterBohdan Wasylyk
Dec 13, 2005·American Journal of Physiology. Endocrinology and Metabolism·Maria G Buse
Nov 26, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Boglarka LaczyJohn C Chatham
Sep 25, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Praveen K VayalilRui-Ming Liu
Apr 11, 2012·International Journal of Vascular Medicine·Steven Daniel FunkA Wayne Orr
Nov 25, 2006·American Journal of Nephrology·Hui LiNong Zhang
Oct 30, 2010·Circulation Research·Ferdinando Giacco, Michael Brownlee
Nov 5, 2002·Journal of Clinical Pharmacology·James P TsikourisGary E Meyerrose
Jul 18, 2009·Molecular Endocrinology·Ushma R JagFrederick M Stanley
Jun 3, 2014·International Journal of Endocrinology·Reddemma SandireddyAshutosh Kumar
Feb 13, 2002·Clinical Cornerstone·J R Sowers
Jan 26, 2016·Critical Reviews in Biochemistry and Molecular Biology·Sherket B Peterson, Gerald W Hart
Dec 16, 2005·The American Journal of the Medical Sciences·Gurushankar GovindarajanJames R Sowers
Feb 11, 2003·Journal of Cellular Biochemistry·Mireille RossignolMichael Klagsbrun
Dec 4, 2014·Diabetes & Metabolic Syndrome·Manal Shakeel
Nov 18, 2008·Metabolism: Clinical and Experimental·Yukio IkedaKozo Hashimoto
May 19, 2007·Molecular and Cellular Endocrinology·Shojiro InadaKozo Hashimoto
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·D E Vaughan

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.