Pharmacogenomics of cardiovascular pharmacology: development of an informatics system for analysis of DNA microarray data with a focus on lipid metabolism.
Genome-wide gene-expression data from DNA-microarray technology and molecular-network data from computational text-mining have led to a paradigm shift in biological research. However, interpretation of the huge amount of data is a bottleneck. We have developed an informatics system, which we refer to as bioSpace Explorer, that can extract pathways and molecules of interest from genome-wide data and show the mutual relationships among these pathways and molecules. Differentiation of 3T3-L1 cells into adipocytes and the action of a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist or alpha-linolenic acid on this process was analyzed with bioSpace Explorer. The results suggested a biological basis for adipocyte differentiation and a strategy to enhance lipid oxidation in adipocytes. Clustered changes of molecules were apparent in the insulin, Wnt, and PPARgamma signaling pathways and in the lipogenesis, lipid oxidation, and lipid transport pathways during cell differentiation. A PPARgamma agonist enhanced lipid oxidation in adipocytes and alpha-linolenic acid gave similar results to the PPARgamma agonist. An analysis of sex hormone and thyroid hormone, in addition to PPARgamma signaling, suggested that these molecules are important for enhancement of lipid oxidation in adipocytes. The results indicate the utility of bioSpace Explorer for biological research on genome-wide molecular networks.
Takahara
Yoshiyuki
Y
PharmaFrontier Co., Ltd., Japan. ytakahara@pharmafrontier.co.jp
Kobayashi
Tomoko
T
Takemoto
Kazuhisa
K
Adachi
Tetsuya
T
Osaki
Ken
K
Kawahara
Kozo
K
Tsujimoto
Gozoh
G
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D019295:Computational Biology; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D047495:PPAR gamma / Q000819:agonists; D010597:Pharmacogenetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D017962:alpha-Linolenic Acid / Q000494:pharmacology
D002317:Cardiovascular Agents; D047495:PPAR gamma; D017962:alpha-Linolenic Acid