Name
Abstract | ||
|---|---|---|
Statins are the most widely used cholesterol-lowering drugs. The primary target of statins is HMG-CoA reductase, a key enzyme in cholesterol synthesis. However, statins elicit pleitropic responses including beneficial as well as adverse effects in the liver or other organs. Today, the regulatory mechanisms that cause these pleiotropic effects are not sufficiently understood.In this work, genome-wide RNA expression changes in primary human hepatocytes of six individuals were measured at up to six time points upon atorvastatin treatment. A computational analysis workflow was applied to reconstruct regulatory mechanisms based on these drug-response data and available knowledge about transcription factor (TF) binding specificities and protein-drug interactions. Several previously unknown TFs were predicted to be involved in atorvastatin-responsive gene expression. The novel relationships of nuclear receptors NR2C2 and PPARA on CYP3A4 were successfully validated in wet-lab experiments.Microarray data are available at the Gene Expression Omnibus (GEO) database at www.ncbi.nlm.nih.gov/geo/, under accession number GSE29868.andreas.zell@uni-tuebingen.de; adrian.schroeder@uni-tuebingen.deSupplementary data are available at Bioinformatics online. |
Year | DOI | Venue |
|---|---|---|
2011 | 10.1093/bioinformatics/btr416 | Bioinformatics |
Keywords | Field | DocType |
cholesterol-lowering drug,supplementary data,regulatory mechanism,response data,regulatory relationship,genome-wide rna expression change,drug interaction,microarray data,primary human hepatocytes,statin-induced gene,atorvastatin-responsive gene expression,available knowledge,de supplementary information | Gene,Testicular receptor 4,Biology,Nuclear receptor,Gene expression,Atorvastatin,Microarray analysis techniques,Bioinformatics,Statin,Transcription factor | Journal |
Volume | Issue | ISSN |
27 | 18 | 1367-4811 |
Citations | PageRank | References |
3 | 0.44 | 9 |
Authors | ||
10 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Adrian Schröder | 1 | 38 | 3.45 |
| Johannes Wollnik | 2 | 4 | 0.80 |
| Clemens Wrzodek | 3 | 113 | 7.11 |
| Andreas Dräger | 4 | 292 | 22.16 |
| Michael Bonin | 5 | 3 | 0.44 |
| Oliver Burk | 6 | 3 | 0.44 |
| Maria Thomas | 7 | 3 | 1.12 |
| Wolfgang E Thasler | 8 | 13 | 1.61 |
| Ulrich M Zanger | 9 | 12 | 1.89 |
| Andreas Zell | 10 | 1419 | 137.58 |