SHERP

Hepatic Gene Expression Profiling and Lipid Homeostasis in Mice Exposed to Steatogenic Drug, Tetracycline

Cited 0 time in webofscience Cited 0 time in scopus
Authors
Yin, Hu-Quan; Kim, Mingoo; Kim, Ju-Han; Kong, Gu; Lee, Mi-Ock; Kang, Kyung-Sun; Yoon, Byung-Il; Kim, Hyung-Lae; Lee, Byung-Hoon
Issue Date
2006-08-17
Publisher
Oxford University Press
Citation
Toxicol. Sci. 94, 206–216
Keywords
tetracyclinemicrovesicular steatosistoxicogenomicslipid metabolismmicroarray
Abstract
Tetracycline is one of a group of drugs known to induce microvesicular steatosis. In the present study, we investigated the effects of tetracycline on gene expression in mouse liver, using Applied Biosystems Mouse Genome Survey Microarrays. A single oral dose of 0.1 or 1 g/kg tetracycline was administered to male ICR mice, and liver samples were obtained after 6, 24, or 72 h. Histopathological evaluation showed microvesicular steatosis in the high-dose group at 24 h. In total, 96 genes were identified as tetracycline responsive. Their level of expression differed significantly from controls (two-way analysis of variance; p < 0.05), after adjustment by the Benjamini-Hochberg multiple testing correction, and displayed a twofold or greater induction or repression. The largest groups of gene products affected by tetracycline exposure were those involved in signal transduction, nucleic acid metabolism, developmental processes, and protein metabolism. The expression of genes known to be involved in lipid metabolism was examined, using two-sample Student's t-test for each treatment group versus a corresponding control group. The overall net effects on expression of lipid metabolism genes indicated an increase in cholesterol and triglyceride biosynthesis and a decrease in ß-oxidation of fatty acids. Our data support a proposed mechanism for tetracycline-induced steatogenic hepatotoxicity that involves these processes. Moreover, we demonstrated global changes in hepatic gene expression following tetracycline exposure; many of these genes have the potential to be used as biomarkers of exposure to steatogenic hepatotoxic agents.
ISSN
1096-6080
Language
English
URI
http://hdl.handle.net/10371/6506
DOI
https://doi.org/10.1093/toxsci/kfl078
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse