Profiling of gene expression in rat liver and rat primary cultured hepatocytes treated with peroxisome proliferators

Kotaro Tamura, Atsushi Ono, Toshikazu Miyagishima, Taku Nagao, Tetsuro Urushidani

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)471-490
Number of pages20
JournalJournal of Toxicological Sciences
Volume31
Issue number5
DOIs
Publication statusPublished - Dec 2006
Externally publishedYes

Fingerprint

Peroxisome Proliferators
Peroxisome Proliferator-Activated Receptors
Gene Expression Profiling
Gene expression
Liver
Rats
Hepatocytes
Benzbromarone
Genes
Databases
Valproic Acid
Non-Steroidal Anti-Inflammatory Agents
Aspirin
Cluster Analysis
Toxicogenetics
Gemfibrozil
Clofibrate
Diclofenac
Cell proliferation
Principal Component Analysis

Keywords

  • Hepatotoxicity
  • Peroxisome proliferator
  • Toxicogenomics

ASJC Scopus subject areas

  • Toxicology

Cite this

Profiling of gene expression in rat liver and rat primary cultured hepatocytes treated with peroxisome proliferators. / Tamura, Kotaro; Ono, Atsushi; Miyagishima, Toshikazu; Nagao, Taku; Urushidani, Tetsuro.

In: Journal of Toxicological Sciences, Vol. 31, No. 5, 12.2006, p. 471-490.

Research output: Contribution to journalArticle

Tamura, Kotaro ; Ono, Atsushi ; Miyagishima, Toshikazu ; Nagao, Taku ; Urushidani, Tetsuro. / Profiling of gene expression in rat liver and rat primary cultured hepatocytes treated with peroxisome proliferators. In: Journal of Toxicological Sciences. 2006 ; Vol. 31, No. 5. pp. 471-490.
@article{3b399d13d0374cc79fd6da051ad6b6d0,
title = "Profiling of gene expression in rat liver and rat primary cultured hepatocytes treated with peroxisome proliferators",
abstract = "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.",
keywords = "Hepatotoxicity, Peroxisome proliferator, Toxicogenomics",
author = "Kotaro Tamura and Atsushi Ono and Toshikazu Miyagishima and Taku Nagao and Tetsuro Urushidani",
year = "2006",
month = "12",
doi = "10.2131/jts.31.471",
language = "English",
volume = "31",
pages = "471--490",
journal = "Journal of Toxicological Sciences",
issn = "0388-1350",
publisher = "Japanese Society of Toxicological Sciences",
number = "5",

}

TY - JOUR

T1 - Profiling of gene expression in rat liver and rat primary cultured hepatocytes treated with peroxisome proliferators

AU - Tamura, Kotaro

AU - Ono, Atsushi

AU - Miyagishima, Toshikazu

AU - Nagao, Taku

AU - Urushidani, Tetsuro

PY - 2006/12

Y1 - 2006/12

N2 - 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.

AB - 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.

KW - Hepatotoxicity

KW - Peroxisome proliferator

KW - Toxicogenomics

UR - http://www.scopus.com/inward/record.url?scp=33846012209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846012209&partnerID=8YFLogxK

U2 - 10.2131/jts.31.471

DO - 10.2131/jts.31.471

M3 - Article

VL - 31

SP - 471

EP - 490

JO - Journal of Toxicological Sciences

JF - Journal of Toxicological Sciences

SN - 0388-1350

IS - 5

ER -