Posttranslational, Reversible O-Glycosylation Is Stimulated by High Glucose and Mediates Plasminogen Activator Inhibitor-1 Gene Expression and Sp1 Transcriptional Activity in Glomerular Mesangial Cells

Endocrinology ◽  
2005 ◽  
Vol 147 (1) ◽  
pp. 222-231 ◽  
Author(s):  
H. J. Goldberg
Keyword(s):  
Gene Expression ◽  
Plasminogen Activator ◽  
High Glucose ◽  
Transcriptional Activity ◽  
Mesangial Cells ◽  
Plasminogen Activator Inhibitor ◽  
Glomerular Mesangial Cells ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor

scholarly journals Posttranslational, Reversible O-Glycosylation Is Stimulated by High Glucose and Mediates Plasminogen Activator Inhibitor-1 Gene Expression and Sp1 Transcriptional Activity in Glomerular Mesangial Cells

Endocrinology ◽  
2006 ◽  
Vol 147 (1) ◽  
pp. 222-231 ◽  
Author(s):  
Howard J. Goldberg ◽  
Catharine I. Whiteside ◽  
Gerald W. Hart ◽  
I. George Fantus
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
High Glucose ◽  
Mesangial Cells ◽  
Plasminogen Activator Inhibitor ◽  
Glomerular Mesangial Cells ◽  
Plasminogen Activator Inhibitor 1 ◽  
Protein Levels ◽  
Activator Inhibitor ◽  
Pai 1

Metabolic flux through the hexosamine biosynthetic pathway (HBP) is increased in the presence of high glucose (HG) and potentially stimulates the expression of genes associated with the development of diabetic nephropathy. A number of synthetic processes are coupled to the HBP, including enzymatic intracellular O-glycosylation (O-GlcNAcylation), the addition of single O-linked N-acetylglucosamine monosaccharides to serine or threonine residues. Despite much data linking flow through the HBP and gene expression, the exact contribution of O-GlcNAcylation to HG-stimulated gene expression remains unclear. In glomerular mesangial cells, HG-stimulated plasminogen activator inhibitor-1 (PAI-1) gene expression requires the HBP and the transcription factor, Sp1. In this study, the specific role of O-GlcNAcylation in HG-induced PAI-1 expression was tested by limiting this modification with a dominant-negative O-linked N-acetylglucosamine transferase, by overexpression of neutral β-N-acetylglucosaminidase, and by knockdown of O-linked β-N-acetylglucosamine transferase expression by RNA interference. Decreasing O-GlcNAcylation by these means inhibited the ability of HG to increase endogenous PAI-1 mRNA and protein levels, the activity of a PAI-1 promoter-luciferase reporter gene, and Sp1 transcriptional activation. Conversely, treatment with the β-N-acetylglucosaminidase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate, in the presence of normal glucose increased Sp1 O-GlcNAcylation and PAI-1 mRNA and protein levels. These findings demonstrate for the first time that among the pathways served by the HBP, O-GlcNAcylation, is obligatory for HG-induced PAI-1 gene expression and Sp1 transcriptional activation in mesangial cells.

Bezafibrate Induces Plasminogen Activator Inhibitor-1 Gene Expression in a CLOCK-Dependent Circadian Manner

2010 ◽  
Vol 78 (1) ◽  
pp. 135-141 ◽  
Author(s):  
Katsutaka Oishi ◽  
Satoru Koyanagi ◽  
Naoya Matsunaga ◽  
Koji Kadota ◽  
Eriko Ikeda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor

Early genetic responses in rat vascular tissue after simulated diving

2012 ◽  
Vol 44 (24) ◽  
pp. 1201-1207 ◽  
Author(s):  
Ingrid Eftedal ◽  
Arve Jørgensen ◽  
Ragnhild Røsbjørgen ◽  
Arnar Flatberg ◽  
Alf O. Brubakk
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Plasminogen Activator ◽  
Differential Gene Expression ◽  
Vascular Function ◽  
Plasminogen Activator Inhibitor ◽  
Fine Tuning ◽  
Plasminogen Activator Inhibitor 1 ◽  
Differential Gene ◽  
Activator Inhibitor

Diving causes a transient reduction of vascular function, but the mechanisms behind this are largely unknown. The aim of this study was therefore to analyze genetic reactions that may be involved in acute changes of vascular function in divers. Rats were exposed to 709 kPa of hyperbaric air (149 kPa Po2) for 50 min followed by postdive monitoring of vascular bubble formation and full genome microarray analysis of the aorta from diving rats ( n = 8) and unexposed controls ( n = 9). Upregulation of 23 genes was observed 1 h after simulated diving. The differential gene expression was characteristic of cellular responses to oxidative stress, with functions of upregulated genes including activation and fine-tuning of stress-responsive transcription, cytokine/cytokine receptor signaling, molecular chaperoning, and coagulation. By qRT-PCR, we verified increased transcription of neuron-derived orphan receptor-1 ( Nr4a3), plasminogen activator inhibitor 1 ( Serpine1), cytokine TWEAK receptor FN14 ( Tnfrsf12a), transcription factor class E basic helix-loop-helix protein 40 ( Bhlhe40), and adrenomedullin ( Adm). Hypoxia-inducible transcription factor HIF1 subunit HIF1-α was stabilized in the aorta 1 h after diving, and after 4 h there was a fivefold increase in total protein levels of the procoagulant plasminogen activator inhibitor 1 (PAI1) in blood plasma from diving rats. The study did not have sufficient power for individual assessment of effects of hyperoxia and decompression-induced bubbles on postdive gene expression. However, differential gene expression in rats without venous bubbles was similar to that of all the diving rats, indicating that elevated Po2 instigated the observed genetic reactions.

Sign in / Sign up

Export Citation Format

Share Document