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Open Access Methodology article

The Sterolgene v0 cDNA microarray: a systemic approach to studies of cholesterol homeostasis and drug metabolism

Tadeja Režen1, Peter Juvan2, Klementina Fon Tacer1, Drago Kuzman3, Adrian Roth4, Denis Pompon5, Lawrence P Aggerbeck5, Urs A Meyer4 and Damjana Rozman1*

Author Affiliations

1 Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Zaloška 4, SI-1000 Ljubljana, Slovenia

2 Artificial Intelligence Laboratory, Faculty of Computer and Information Science, University of Ljubljana, Tržaška cesta 25, SI-1000, Slovenia

3 Lek Pharmaceuticals d.d., Verovškova 57, SI-1000 Ljubljana, Slovenia

4 Genome Scale Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland

5 CNRS, Avenue de la Terrasse, F-91198 Gif-sur-Yvette, France

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BMC Genomics 2008, 9:76  doi:10.1186/1471-2164-9-76

Published: 11 February 2008

Abstract

Background

Cholesterol homeostasis and xenobiotic metabolism are complex biological processes, which are difficult to study with traditional methods. Deciphering complex regulation and response of these two processes to different factors is crucial also for understanding of disease development. Systems biology tools as are microarrays can importantly contribute to this knowledge and can also discover novel interactions between the two processes.

Results

We have developed a low density Sterolgene v0 cDNA microarray dedicated to studies of cholesterol homeostasis and drug metabolism in the mouse. To illustrate its performance, we have analyzed mouse liver samples from studies focused on regulation of cholesterol homeostasis and drug metabolism by diet, drugs and inflammation. We observed down-regulation of cholesterol biosynthesis during fasting and high-cholesterol diet and subsequent up-regulation by inflammation. Drug metabolism was down-regulated by fasting and inflammation, but up-regulated by phenobarbital treatment and high-cholesterol diet. Additionally, the performance of the Sterolgene v0 was compared to the two commercial high density microarray platforms: the Agilent cDNA (G4104A) and the Affymetrix MOE430A GeneChip. We hybridized identical RNA samples to the commercial microarrays and showed that the performance of Sterolgene is comparable to commercial arrays in terms of detection of changes in cholesterol homeostasis and drug metabolism.

Conclusion

Using the Sterolgene v0 microarray we were able to detect important changes in cholesterol homeostasis and drug metabolism caused by diet, drugs and inflammation. Together with its next generations the Sterolgene microarrays represent original and dedicated tools enabling focused and cost effective studies of cholesterol homeostasis and drug metabolism. These microarrays have the potential of being further developed into screening or diagnostic tools.