Back to Search
Start Over
β 3 -Adrenergic receptor regulates hepatic apolipoprotein A-I gene expression.
- Source :
-
Journal of clinical lipidology [J Clin Lipidol] 2017 Sep - Oct; Vol. 11 (5), pp. 1168-1176. Date of Electronic Publication: 2017 Jul 27. - Publication Year :
- 2017
-
Abstract
- Background: β <subscript>3</subscript> -adrenergic receptor (β <subscript>3</subscript> -AR) was shown to upregulate hepatic apolipoprotein A-I (apoA-I) expression and reverse atherosclerotic plaques in vivo experiments. However, the effect of β <subscript>3</subscript> -AR on apoA-I expression in vitro is unknown. The specific mechanism underlying β <subscript>3</subscript> -AR prevention of atherosclerosis is unclear.<br />Objective: The present study was designed to investigate the molecular mechanism of β <subscript>3</subscript> -AR-mediated regulation of hepatic apoA-I gene expression.<br />Methods: HepG2 cells were preincubated with/without a selective protein kinase A inhibitor (H-89) and then treated with a selective β <subscript>3</subscript> -AR agonist (BRL37344) or antagonist (SR59230A). The hepatic apoA-I expression was detected by reverse transcription real-time quantitative polymerase chain reaction and Western blot analysis. Enzyme-linked immunosorbent assay was used to evaluate the secretion of apoA-I. A recombinant plasmid containing the apoA-I promoter was constructed and transiently transfected into HepG2 cells, and dual-luciferase reporter assays were used to examine the activity of the apoA-I promoter. A chromatin immunoprecipitation polymerase chain reaction assay was used to evaluate binding activities of hepatocyte nuclear factor-4 (HNF-4), HNF-3, and early growth response protein-1.<br />Results: β <subscript>3</subscript> -AR activation significantly upregulated apoA-I expression, promoted apoA-I secretion, and enhanced the activities of the apoA-I promoter, HNF-4, and HNF-3 in hepatocytes, whereas early growth response protein-1 was not affected. Moreover, protein kinase A inhibition partially suppressed the activation of the apoA-I promoter, HNF-4, and HNF-3 and almost completely blocked the upregulation of apoA-I expression induced by β <subscript>3</subscript> -AR.<br />Conclusion: β <subscript>3</subscript> -AR activation increased the activities of the apoA-I promoter, HNF-4, and HNF-3, which might account for the mechanism of β <subscript>3</subscript> -AR-mediated upregulation of hepatic apoA-I expression. β <subscript>3</subscript> -AR might exert an anti-atherosclerotic effect by upregulating hepatic apoA-I expression and promoting the cholesterol reverse transport process.<br /> (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adrenergic beta-3 Receptor Agonists pharmacology
Adrenergic beta-3 Receptor Antagonists pharmacology
Cyclic AMP metabolism
Cyclic AMP-Dependent Protein Kinases metabolism
Dose-Response Relationship, Drug
Hep G2 Cells
Hepatocyte Nuclear Factor 3-alpha metabolism
Hepatocyte Nuclear Factor 4 metabolism
Hepatocytes cytology
Hepatocytes drug effects
Hepatocytes metabolism
Humans
Liver cytology
Promoter Regions, Genetic genetics
Protein Kinase Inhibitors pharmacology
Signal Transduction drug effects
Apolipoprotein A-I genetics
Gene Expression Regulation drug effects
Liver metabolism
Receptors, Adrenergic, beta-3 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1933-2874
- Volume :
- 11
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of clinical lipidology
- Publication Type :
- Academic Journal
- Accession number :
- 28802864
- Full Text :
- https://doi.org/10.1016/j.jacl.2017.07.007