| The Effects of Rosuvastatin and the CYP51A1 Inhibitor LEK-935 on the Proteome of Primary Human Hepatocytes. | |
| | |
MedLine Citation:
|
PMID: 22180046 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Elevated amounts of cholesterol are thought to be involved in several severe diseases. Despite of the fact that many studies have been performed and published, the action of cholesterol lowering agents used to diminish the plasma cholesterol level is not fully understood yet. In this study, the effects of the HMG-CoA reductase inhibitor rosuvastatin and the new CYP51A1 inhibitor LEK-935 on the proteome of primary human hepatocytes were analysed for the first time. To get an idea about inter-individual differences two different human donors were used. The cytosolic and microsomal fractions of the cells were analysed in a semi-quantitative manner by 2D- PAGE and capillary HPLC-MS, respectively. Thereby, a set of 44 proteins was found to be differentially presented. The chosen experimental set-up was validated by proteins already known to be affected by statins and involved in the cholesterol biosynthesis. Other proteins found to be regulated cannot be directly related to cholesterol metabolism and have not been described to be affected by cholesterol lowering agents so far. Some of these proteins may represent interesting targets for further investigations towards the analysis of severe side-effects as well as pleiotropic effects of the statins. During the proteome analysis of the two different donors, inter-individual differences were observed that were validated by RT-PCR measurements. Thus, new information and a deeper insight into the processes taking place inside cells treated with cholesterol lowering agents can be drawn from this study. |
| | |
Authors:
|
Martin Woerner; Katja Melchior; Katalin Monostory; Jean-Marc Pascussi; Christian G Huber; Rita Bernhardt |
Related Documents
:
|
3946096 - The effect of dietary nitrite and nitrate on the metabolism of sulphamethazine in the rat. 17701746 - Determination of isocyanate biomarkers in construction site workers. 7867906 - Comparison of renal toxicity after long-term oral administration of cadmium chloride an... 3732666 - The effect of an unusual workshift on chemical toxicity. ii. studies on the exposure of... 6639526 - Factors predisposing dairy and beef cows to grass tetany. 16109306 - Optimization of selenium status by a single intraperitoneal injection of se in se-defic... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-12-16 |
Journal Detail:
|
Title: Drug metabolism and disposition: the biological fate of chemicals Volume: - ISSN: 1521-009X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2011-12-19 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
1 Saarland university; |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Characterization of Hepatic and Intestinal Glucuronidation of Magnolol: Application of the RAF Appro...
Next Document: Pharmacokinetics, Distribution, and Metabolism of [14C]sunitinib in Rats, Monkeys, and Humans.