Evidence for enhanced expression of c-fos, c-jun, and the Ca(2+)-activated neutral protease in rat liver following carbon tetrachloride administration.
The effects of CCl4 on hepatic c-fos and c-jun gene expression were examined, and the correspondence between intermediate-early gene expression and the expression of the Ca(2+)-activated neutral proteinase (mu and mCANP) characterized. Administration of CCl4 to rats resulted in a pronounced dose- and time-dependent increase in c-jun and c-fos mRNA levels (approximately 8 to 17-fold) as detected by either Northern blot or RT-PCR analyses. The expression of mu and mCANP following CCl4 treatment was monitored by Northern blot analysis and mu and mCANP mRNA levels were found to be elevated approximately 5- to 15-fold over the time period of 18 to 24 h. Experiments were performed to determine whether the Fos-Jun heterodimeric AP-1 transcription factor complex bound the AP-1-like binding motif present in the mCANP gene. Gel retardation assays using hepatic nuclear extracts from CCl4-treated animals revealed binding of a protein to the AP-1-like motif present in the mCANP gene and competition and supershift assays confirmed the specificity of AP-1 transcription factor binding. These results show that CANP gene expression is enhanced in response to oxidative cellular damage and that the AP-1 complex may be involved in the regulation of CANP gene expression.
Zawaski
K
K
Institute of Chemical Toxicology, Wayne State University, Detroit, MI 48201.
Gruebele
A
A
Kaplan
D
D
Reddy
S
S
Mortensen
A
A
Novak
R F
RF
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002154:Calpain / Q000096:biosynthesis*; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D015342:DNA Probes; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D016133:Polymerase Chain Reaction; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015342:DNA Probes; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D002251:Carbon Tetrachloride; D002154:Calpain