Modulation of gene and protein expression by carbon tetrachloride in the rat liver.
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 (CCl(4)) on the gene and protein expression in rat livers. Adult Wistar rats were administered CCl(4) 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, alpha-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 CCl(4) 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.
Fountoulakis
Michael
M
Genetics (PRGT), F. Hoffmann-La Roche AG, 4070 Basle, Switzerland.
de Vera
Maria-Christina
MC
Crameri
Flavio
F
Boess
Franziska
F
Gasser
Rodolfo
R
Albertini
Silvio
S
Suter
Laura
L
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002251:Carbon Tetrachloride