caa a22 4500 445852887 CHVBK 20180317145418.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s00204-010-0632-7 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0632-7 Hepatic transcriptome and proteome responses against diethyl maleate-induced glutathione depletion in the rat [Elektronische Daten] [Shusuke Yamauchi, Naoki Kiyosawa, Yosuke Ando, Kyoko Watanabe, Noriyo Niino, Kazumi Ito, Takashi Yamoto, Sunao Manabe, Atsushi Sanbuissho] Hepatic transcriptome and proteome responses against glutathione depletion were investigated by Affymetrix GeneChip Microarray and 2-dimensional gel electrophoresis (2D-DIGE), followed by MALDI-TOF-MS analysis and utilizing a glutathione-depleted rat model treated with diethyl maleate (DEM). Hepatic glutathione content decreased to 1.29μmol/g liver (25.5% compared to control) after DEM treatment, and there were no apparent hepatotoxic signs estimated by blood chemistry examinations. A total of 247 and 213 annotated gene probe sets exhibited greater than twofold up- and down-regulation compared with controls, respectively. The up-regulated gene list contained a number of glutathione depletion-responsive genes reported previously, such as Trib3, Srxn1, Myc, Asns, Igfbp1, Txnrd1, or Hmox1, suggesting that these genes are robust mRNA biomarkers for evaluating hepatic glutathione depletion. In the 2D-DIGE analysis, proteins for a total of 361 spots were identified by MALDI-TOF-MS analysis. Of the identified proteins, 5 and 14 proteins showed up- and down-regulation, respectively. Some proteins exhibited differential expression in the protein level but not in the mRNA level, including L-FABP, MAWDBP, aldo-keto reductase family 1 member A1, catalase and ATP synthase subunit beta, suggesting that these proteins would be potential protein biomarkers for evaluating glutathione depletion. Moreover, up-regulation of FABP1 protein along with up-regulation of PPARα-regulated gene transcripts (i.e., Acot2 and Acot4) is indicative of PPARα activation, which may contribute to hepatocellular protection against glutathione depletion-induced oxidative stress. The up-regulation of L-FABP1 was detected by proteome data but not by transcriptome data, demonstrating the advantage of utilizing transcriptomics and proteomics combination to investigate glutathione depletion-induced molecular dynamics. Springer-Verlag, 2010 Liver nationallicence Glutathione nationallicence Microarray nationallicence Proteomics nationallicence Toxicogenomics nationallicence Yamauchi Shusuke Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut Kiyosawa Naoki Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut Ando Yosuke Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut Watanabe Kyoko Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut Niino Noriyo Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut Ito Kazumi Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut Yamoto Takashi Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut Manabe Sunao Global Project Management Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan aut Sanbuissho Atsushi Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut Archives of Toxicology Springer-Verlag 85/9(2011-09-01), 1045-1056 0340-5761 85:9<1045 2011 85 204 https://doi.org/10.1007/s00204-010-0632-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0632-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yamauchi Shusuke Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut NATIONALLICENCE 700 1- Kiyosawa Naoki Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut NATIONALLICENCE 700 1- Ando Yosuke Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut NATIONALLICENCE 700 1- Watanabe Kyoko Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut NATIONALLICENCE 700 1- Niino Noriyo Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut NATIONALLICENCE 700 1- Ito Kazumi Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut NATIONALLICENCE 700 1- Yamoto Takashi Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut NATIONALLICENCE 700 1- Manabe Sunao Global Project Management Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan aut NATIONALLICENCE 700 1- Sanbuissho Atsushi Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/9(2011-09-01), 1045-1056 0340-5761 85:9<1045 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer