scholarly journals Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver

2020 ◽  
Vol 72 (4) ◽  
pp. 555-565
Author(s):  
Vesna Martinovic ◽  
Jelena Arambasic-Jovanovic ◽  
Desanka Bogojevic ◽  
Andjelija Ivanovic ◽  
Vesna Otasevic ◽  
...  
Keyword(s):  
Affinity Chromatography ◽  
Transcription Initiation ◽  
Gene Promoter ◽  
Immunoblot Analysis ◽  
Progressive Increase ◽  
Diabetic Rats ◽  
Transcription Initiation Complex ◽  
Nucleocytoplasmic Proteins ◽  
Responsive Element ◽  
Hormone Responsive Element

Haptoglobin (Hp) is a hemoglobin-binding protein that prevents free hemoglobin-induced tissue oxidative damage. In streptozotocin-induced diabetic rats, the initial elevation of Hp expression in the serum and liver tends to decrease with diabetes progression, contributing to increased oxidative stress. Glucose toxicity and diabetic complications are closely related to increased modification of nucleocytoplasmic proteins by O-linked-N-acetylglucosamine (O-GlcNAc). We examined the contribution of O-GlcNAcylation of NF-?B p65 to changes in liver Hp expression in diabetic rats. WGA-affinity chromatography revealed a progressive increase in O-GlcNAcylation in nuclear NF-?B p65 during eight weeks of diabetes. DNA-affinity chromatography followed by immunoblot analysis revealed that decreased Hp expression at 4 and 8 weeks of diabetes was accompanied by the absence of Hp gene hormone-responsive element (HRE) occupancy with NF-?B p65, low occupancy with glucocorticoid receptor (GR), and almost no changes in STAT3 occupancy compared to 2 weeks, when Hp expression was highest. Coimmunoprecipitation experiments indicate that these events were the result of impaired NF-?B p65/STAT3 and GR/STAT3 interactions. Results suggest that the attenuation of Hp expression associated with diabetes was at least in part the result of O-GlcNAcylation of NF-?B p65, which prevents the formation of an effective transcription initiation complex on the Hp gene promoter.

scholarly journals Association of the glucocorticoid receptor with STAT3, C/EBPβ, and the hormone-responsive element within the rat haptoglobin gene promoter during the acute phase response

IUBMB Life ◽  
2010 ◽  
Vol 62 (3) ◽  
pp. 227-236 ◽  
Author(s):  
Jelena Arambašić ◽  
Goran Poznanović ◽  
Svetlana Ivanović-Matić ◽  
Desanka Bogojević ◽  
Mirjana Mihailović ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Gene Promoter ◽  
Phase Response ◽  
Responsive Element ◽  
Hormone Responsive Element ◽  
Haptoglobin Gene

scholarly journals Identification of a TPA-responsive element mediating preferential transactivation of the galanin gene promoter in chromaffin cells.

1994 ◽  
Vol 269 (9) ◽  
pp. 6823-6831
Author(s):  
Y. Anouar ◽  
L. MacArthur ◽  
J. Cohen ◽  
A.L. Iacangelo ◽  
L.E. Eiden
Keyword(s):  
Chromaffin Cells ◽  
Gene Promoter ◽  
Responsive Element

scholarly journals Intestinal Apolipoprotein A-IV Gene Transcription Is Controlled by Two Hormone-Responsive Elements: A Role for Hepatic Nuclear Factor-4 Isoforms

2005 ◽  
Vol 19 (9) ◽  
pp. 2320-2334 ◽  
Author(s):  
Amena Archer ◽  
Dominique Sauvaget ◽  
Valérie Chauffeton ◽  
Pierre-Etienne Bouchet ◽  
Jean Chambaz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mice ◽  
Distal Region ◽  
Proximal Region ◽  
Dominant Negative ◽  
Specific Expression ◽  
Nuclear Factors ◽  
Dominant Negative Form ◽  
Responsive Element ◽  
Hormone Responsive Element

Abstract In the small intestine, the expression of the apolipoprotein (apo) C-III and A-IV genes is restricted to the enterocytes of the villi. We have previously shown that, in transgenic mice, specific expression of the human apo C-III requires a hormone-responsive element (HRE) located in the distal region of the human apoA-IV promoter. This HRE binds the hepatic nuclear factors (HNF)-4α and γ. Here, intraduodenal injections in mice and infections of human enterocytic Caco-2/TC7 cells with an adenovirus expressing a dominant-negative form of HNF-4α repress the expression of the apoA-IV gene, demonstrating that HNF-4 controls the apoA-IV gene expression in enterocytes. We show that HNF-4α and γ functionally interact with a second HRE present in the proximal region of the human apoA-IV promoter. New sets of transgenic mice expressing mutated forms of the promoter, combined with the human apo C-III enhancer, demonstrate that, whereas a single HRE is sufficient to reproduce the physiological cephalo-caudal gradient of apoA-IV gene expression, both HREs are required for expression that is restricted to villi. The combination of multiple HREs may specifically recruit regulatory complexes associating HNF-4 and either coactivators in villi or corepressors in crypts.

Molecular cloning of the murine adenosine deaminase gene from a genetically enriched source: identification and characterization of the promoter region

1986 ◽  
Vol 6 (12) ◽  
pp. 4458-4466
Author(s):  
D E Ingolia ◽  
M R Al-Ubaidi ◽  
C Y Yeung ◽  
H A Bigo ◽  
D Wright ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Structural Gene ◽  
Transcription Initiation ◽  
Genomic Library ◽  
Gene Promoter ◽  
Mouse Cell ◽  
Gene Promoters ◽  
Sp1 Transcription Factor ◽  
Base Pair Fragment ◽  
Functional Analyses

A genomic library was prepared with DNA from a genetically enriched mouse cell line in which amplified copies of the adenosine deaminase (ADA) gene account for over 5% of the genome. Overlapping cosmid clones encompassing the entire ADA structural gene were isolated from this genomic library and used for subsequent structural and functional analyses. Nuclease protection and primer extension analyses served to identify the location of multiple transcription initiation sites at the 5' end of the structural gene. Promoter activity was found by functional analyses to reside within a 240-base-pair fragment which contains the transcription initiation sites. Sequences upstream of the transcription initiation sites are very G + C rich (77%) and include a 22 nucleotide stretch of deoxyguanylate residues and two potential Sp1 transcription factor-binding sites. Comparison of the mouse and human ADA gene promoters revealed the presence of several regions that are highly conserved with regard to both sequence content and location and may represent genetic elements which are involved in ADA gene expression.

Abstract O-1: Klf5 Regulates Cardiac Pparα and Med13 and affects Cardiac Fatty Acid Metabolism And Obesity

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Konstantinos Drosatos ◽  
Nina Pollak ◽  
Panagiotis Ntziachristos ◽  
Chad M Trent ◽  
Yunying Hu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Binding Sites ◽  
Transcription Initiation ◽  
Acid Metabolism ◽  
Gene Promoter ◽  
Initiation Site ◽  
White Adipocytes ◽  
Metabolic Role

Krüppel-like factors (KLF) have been associated with metabolic phenotypes. Our study focused on the metabolic role of cardiac KLF5, as it showed the highest increase among all KLFs that were detected by whole genome microarrays of energy-starved hearts obtained from lipopolysaccharide (LPS)-treated mice. Analysis of ppara promoter indicated two potential binding sites for c-Jun (AP-1 sites), the transcriptional factor that is activated by LPS and reduces cardiac PPARα expression: −792/-772 bp and −719/-698 bp prior to the transcription initiation site. This analysis showed that both AP-1 sites overlap with potential KLF-binding sites. Adenovirus-mediated expression of constitutively active c-Jun in a mouse cardiomyocyte cell line (HL-1) reduced PPARα gene expression, while treatment with Ad-KLF5 had the opposite effect. Chromatin immunoprecipitation analysis (ChIP) showed that c-Jun binds both −792/-772 bp and −719/-698 sites of ppara promoter while KLF5 binds on −792/-772 bp. ChIP analysis also showed that LPS promotes c-Jun binding on −792/-772 bp, which prohibits occupation of this region by KLF5. A cardiomyocyte-specific KLF5 knockout mouse (αMHC-KLF5-/-) had normal cardiac function but reduced cardiac expression of PPARα (50%) and other fatty acid metabolism-associated genes such as CD36 (40%), LpL (20%), PGC1α (45%), AOX (28%) and Cpt1 (45%). High fat diet (HFD)-fed αMHC-KLF5-/- mice had a more profound body weight increase (35%) compared to HFD-fed WT mice (15%), as well as larger white adipocytes and brown adipocytes (H&E) and increased hepatic neutral lipid accumulation (Oil-Red-O). The obesogenic effect of cardiomyocyte-specific deletion of KLF5 resembles the phenotype of the αMHC-MED13-/- mice. We showed that KLF5 ablation reduced cardiac MED13 levels despite lack of changes in the expression levels of miR-208, a known regulator of MED13. Infection of HL-1 cells with Ad-KLF5 increased MED13 gene expression. ChIP identified a KLF5 binding site on med13 gene promoter region (-730/-714 bp). Thus, KLF5 regulates cardiac PPARα and MED13 and affects cardiac and systemic fatty acid metabolism and obesity, thus indicating KLF5 as a potential target for cardiac dysfunction associated with energetic complications, as well as for obesity

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