dc.contributor.author | Chen, YQ | |
dc.contributor.author | Su, M | |
dc.contributor.author | Walia, RR | |
dc.contributor.author | Hao, Q | |
dc.contributor.author | Covington, JW | |
dc.contributor.author | Vaughan, DE | |
dc.date.accessioned | 2013-11-06T13:05:15Z | |
dc.date.available | 2013-11-06T13:05:15Z | |
dc.date.issued | 1998 | |
dc.identifier.citation | J Biol Chem. 1998 Apr 3;273(14):8225-31. | en |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/pubmed/9525928 | |
dc.identifier.uri | http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/58260 | |
dc.description.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 effect on two adjacent Sp1 sites located between -85 and -42 bp of the PAI-1 5'-flanking region and that the release of a transcriptional repressor from the Sp1 complexes may explain the activation of the PAI-1 gene under high glucose conditions in RASM cells. | en |
dc.language.iso | en | en |
dc.publisher | University of Nairobi | en |
dc.title | Sp1 sites mediate activation of the plasminogen activator inhibitor-1 promoter by glucose in vascular smooth muscle cells. | en |
dc.type | Article | en |
local.publisher | School of Computing and Informatics | en |