Modulation of Gene and Protein Expression by Carbon Tetrachloride in the Rat Liver

doi:10.1006/taap.2002.9460

Toxicology and Applied Pharmacology

Volume 183, Issue 1, 15 August 2002, Pages 71-80

https://doi.org/10.1006/taap.2002.9460 Get rights and content

Abstract

The gene and protein expression changes after exposure to a toxic compound might help elucidate its mechanism of action. In this paper we investigated the effect of carbon tetrachloride (CCl₄) on the gene and protein expression in rat livers. Adult Wistar rats were administered CCl₄ and livers were harvested 6 or 24 h thereafter. The analysis of mitochondrial proteins on 2D gels showed the upregulation of two proteins involved in stress (catalase and uricase). Among the downregulated proteins, enzymes related to the metabolism of lipids and aminoacids were affected. Additionally, α-2-macroglobulin and senescence marker protein, two proteins whose decrease in expression has been connected to hepatocyte damage, were decreased. Several of the upregulated genes are involved in stress response, DNA and protein damage, and repair. Genes coding for several enzymes involved in different metabolic pathways, including some P450, were downregulated in the treated animals. In conclusion, a single dose of CCl₄ caused gene and protein expression changes that can be related to its mechanism of toxicity. Results from both technologies support previous publications and provide possible new toxicity markers. However, the correlation between gene and protein expression at a given time point is less apparent, partly as a result of different regulatory mechanisms between gene and protein expression.

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In spite of the high stringency criteria used in this study, that permitted identification of very few probes, a good correlation was found with previous studies. Typically, a single dose of CCl4 results in centrilobular cell degeneration and necrosis accompanied by lipid peroxidation along with elevated serum enzyme activities followed by hepatic regeneration, usually starting after 48 h (Fountoulakis et al., 2002). Correspondingly, expression of mRNA in hepatic parenchyma cells generally changes on exposure to a single toxic dose of compound.
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Regular ArticleModulation of Gene and Protein Expression by Carbon Tetrachloride in the Rat Liver

Abstract

Anal Biochem

Hepatology

Hepatology

Toxicol. Appl. Pharmacol.

Toxicol. Appl. Pharmacol.

Toxicol. Lett.

Toxicol. Appl. Pharmacol.

Anal. Biochem.

J. Hepatol.

Mech. Ageing Dev.

Toxicol. Appl. Pharmacol.

Biochem. Biophys. Res. Commun.

Life Sci.

Exp. Gerontol.

Toxicol. Lett.

Gastroenterology

J. Hepatol.

Unique gene expression patterns in liver and kidney associated with exposure to chemical toxicants

J. Pharmacol. Exp. Ther.

Reliable automatic protein identification from matrix-assisted laser desorption/ionization mass spectrometric peptide fingerprints

Electrophoresis

Identification of glutathione S-transferase isozymes and gamma-glutamylcysteine synthetase as negative acute-phase proteins in rat liver

Hepatology

Regular Article
Modulation of Gene and Protein Expression by Carbon Tetrachloride in the Rat Liver