Molecular process in acute liver injury and regeneration induced by carbon tetrachloride.
Injection of carbon tetrachloride (CCl4) intraperitoneally into model animals induces acute liver injury mediated by reactive oxygen species (ROS) as normal metabolites in hepatocytes. In this study, the molecular process in this type of liver injury was analyzed from the aspect of liver function and regulatory factors. Down-regulation of liver-specific genes was accomplished through suppression of liver-enriched transcription factors and box A factors found in the catalase gene, and induction of NF-kappaB, AP-1 and a novel factor denoted as 'cx' in the catalase gene. Expression profiles of these genes were restored to normal levels in the late stage of injury (48 h). On the other hand, hepatocyte growth factor (HGF) and proliferating cell nuclear antigen (PCNA) were induced in the early stage (6 h) and 36 h, respectively. Interestingly, ERK2 was transiently activated at 3 h CCl4-treatment. These observations suggested that hepatotoxin by CCl4-injection concomitantly induces both processes in acute injury and liver regeneration.
Taniguchi
Makoto
M
Division of Molecular Biology, Department of Molecular and Cellular Biology, School of Life Sciences, Tottori University Faculty of Medicine, 86 Nishimachi, Yonago 683-8503, Japan.
Takeuchi
Toshiyuki
T
Nakatsuka
Ryusuke
R
Watanabe
Tatsuo
T
Sato
Kenzo
K
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D029721:Drosophila Proteins; D024202:Electrophoretic Mobility Shift Assay; D050980:GATA Transcription Factors; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D017114:Liver Failure, Acute / Q000139:chemically induced*; D008115:Liver Regeneration / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050980:GATA Transcription Factors; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C103965:srp protein, Drosophila; D017228:Hepatocyte Growth Factor; D002251:Carbon Tetrachloride; D002374:Catalase; D019950:Mitogen-Activated Protein Kinase 1