RGD Reference Report - Regulation mechanism of ABCA1 expression by statins in hepatocytes. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Regulation mechanism of ABCA1 expression by statins in hepatocytes.

Authors: Kobayashi, Masaki  Gouda, Keisuke  Chisaki, Ikumi  Ochiai, Manami  Itagaki, Shirou  Iseki, Ken 
Citation: Kobayashi M, etal., Eur J Pharmacol. 2011 Jul 15;662(1-3):9-14. doi: 10.1016/j.ejphar.2011.04.043. Epub 2011 May 1.
RGD ID: 21408554
Pubmed: PMID:21554872   (View Abstract at PubMed)
DOI: DOI:10.1016/j.ejphar.2011.04.043   (Journal Full-text)

ATP-binding cassette transporter A1 (ABCA1) is predicted to be involved in the control of apolipoprotein AI-mediated cholesterol efflux: biosynthesis of high-density lipoprotein (HDL). However, the effects of HMG-CoA reductase inhibitors (statins) on ABCA1 in the liver and the precise mechanisms of their actions have been obscure. The aims of this study were to determine whether statins (atorvastatin (Ato) and pitavastatin (Pit)) affect hepatic ABCA1 expression and to clarify the mechanisms of their actions using HepG2 cells and the rat liver. We examined alterations in mRNA and protein levels of ABCA1 and peroxisome proliferator-activated receptors (PPARs) by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. In vitro and in vivo studies suggested that Pit increases ABCA1 mRNA level, but not Ato. Pit greatly increased Abca1 mRNA level and also increased the amount of plasma HDL and the mRNA level of PPARα. Clofibrate (PPARα agonist) increased ABCA1 expression in HepG2 cells and rat primary hepatocytes more than did PPAR β/δ and γ agonists. Pit-induced ABCA1 expression alteration was blocked by GW6471 (PPARα antagonist) and by PPARα knockdown. In this study, we demonstrated that Pit affect ABCA1 expression via PPARα in hepatocytes. The strategy to target a PPARα agonist in the liver can lead to increases in ABCA1 expression and HDL level.

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
clofibrate increases expression EXP 21408554clofibrate increases expression of ABCA1 mRNA and protein in HepG2 cellsRGD 
clofibrate increases expression ISOAbca1 (Rattus norvegicus)21408554; 21408554clofibrate increases expression of abca1 mRNA and protein in rat primary hepatocytesRGD 
clofibrate increases expression ISOABCA1 (Homo sapiens)21408554; 21408554clofibrate increases expression of ABCA1 mRNA and protein in HepG2 cellsRGD 
clofibrate increases expression EXP 21408554clofibrate increases expression of abca1 mRNA and protein in rat primary hepatocytesRGD 
GW 6471 decreases expression ISOAbca1 (Rattus norvegicus)21408554; 21408554GW6471 reverses the reaction [pitavastatin increases expression of abca1 mRNA in rat primary hepatocytes]RGD 
GW 6471 decreases expression EXP 21408554GW6471 reverses the reaction [pitavastatin increases expression of abca1 mRNA in rat primary hepatocytes]RGD 
pitavastatin increases expression ISOAbca1 (Rattus norvegicus)21408554; 21408554pitavastatin increases expression of abca1 mRNA in rat liverRGD 
pitavastatin increases expression EXP 21408554pitavastatin increases expression of ABCA1 mRNA in HepG2 cellsRGD 
pitavastatin increases expression ISOABCA1 (Homo sapiens)21408554; 21408554pitavastatin increases expression of ABCA1 mRNA in HepG2 cellsRGD 
pitavastatin increases expression EXP 21408554pitavastatin increases expression of abca1 mRNA in rat liverRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to xenobiotic stimulus  IEP 21408554pitavastatin more ...RGD 
lipoprotein biosynthetic process  IEP 21408554 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abca1  (ATP binding cassette subfamily A member 1)

Genes (Mus musculus)
Abca1  (ATP-binding cassette, sub-family A member 1)

Genes (Homo sapiens)
ABCA1  (ATP binding cassette subfamily A member 1)


Additional Information