PROFILING OF GENE EXPRESSION IN RAT LIVER AND RAT PRIMARY CULTURED HEPATOCYTES TREATED WITH PEROXISOME PROLIFERATORS
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概要
- 論文の詳細を見る
The Toxicogenomics project has been constructing a large-scale database of about 150 compounds exposed to rat (single dose, 3, 6, 9, 24 hrs and repeated dose for 3, 7, 14 28 days with 3 dose levels) and rat hepatocytes (2, 8, 24 hr with 3 concentrations) and data of transcriptome in liver using GeneChip, and the related toxicological measures are being accumulated. In the present study, the data of three ligands of peroxisome proliferator activated receptor α(PPARα), i.e., clofibrate, WY-14643 and gemfibrozil in our database were analyzed. Many of the β-oxidation-related genes were commonly induced in vivo and in vitro, whereas expression changes in genes related to cell proliferation, apoptosis, were detected in vivo (single and repeated dose) but not in vitro. Changes in those related to the immune response, coagulation and the stress response were also detectable exclusively in vivo. Using the genes mobilized in two or three PPARα agonists, hierarchical clustering was performed on 32 compounds stored in our database. In the profiling of an in vivo single dose, benzbromarone and aspirin were located in the same cluster of the three PPARα agonists. The clustering of in vitro data revealed that benzbromarone, three NSAIDs (aspirin, indomethacin and diclofenac sodium) and valproic acid belonged to the same cluster of PPARα agonists, supporting the reports that benzbromarone, valproic acid and some NSAIDs were reported to be PPARα agonists. Using the genes commonly up-regulated both in vivo and in vitro, principal component analysis was performed in 32 compounds, and principal component 1 was found to be the convenient parameter to extract PPARα agonist-like compounds from the database.
- 日本トキシコロジー学会の論文
- 2006-12-15
著者
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NAGAO Taku
National Institute of Health Sciences
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Nagao Taku
Food Safety Commission Of Japan
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Nagao Taku
Laboratory Of Pharmacology & Toxicology Graduate School Of Pharmaceutical Sciences The Universit
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Nagao Taku
Laboratory Of Pharmacology And Toxicology Graduate School Of Pharmaceutical Sciences The University
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Ono Atsushi
Toxicogenomics Project National Institute Of Biomedical Innovation:national Institute Of Health Scie
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Miwa Satoko
Exploratory Toxicology & Dmpk Research Laboratories Tanabe Seiyaku Co. Ltd.
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MIYAGISHIMA Toshikazu
Toxicogenomics Project, National Institute of Biomedical Innovation
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Urushidani Tetsuro
Toxicogenomics Project National Institute Of Biomedical Innovation:department Of Pathophysiology Dos
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Urushidani Tetsuro
Laboratory Of Pharmacology & Toxicology Graduate School Of Pharmaceutical Sciences The Universit
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Miyagishima Toshikazu
Toxicogenomics Project National Institute Of Biomedical Innovation
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Kasahara Toshihiko
Toxicogenomics Project National Institute Of Biomedical Innovation
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Tamura Kotaro
Toxicogenomics Project National Inst. Of Biomedical Innovation
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Nagao Taku
National Institute Of Health Sci.
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Ono Atsushi
Toxicogenomics Project National Institute Of Biomedical Innovation:national Institute Of Health Scie
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Urushidani Tetsuro
Toxicogenomics Project National Institute Of Biomedical Innovation
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