Effects of mercuric chloride on the regulation of expression of the acute phase response components α₁-acid glycoprotein and C/EBP transcription factors

We have previously shown that in response to treatment with HgCl₂, the adult mouse liver exhibits both transcriptional and translational regulation of the acute phase response genes. In this study we asked whether the heavy metal treatment affects the regulation of the C/EBP transcription factors which play a key role in regulation of the acute phase response gene. Our studies have shown that the AGP gene is transcriptionally activated while transcription of the CCAAT/enhancer-binding trans-activating protein (C/EBP)α gene is slightly down-regulated and that of the C/EBPβ gene does not respond. Both the C/EBPα and C/EBPβ mRNAs produce multiple isoforms possibly by alternative translation initiation (ATI) of multiple internal AUG initiation sites. The C/EBPβ mRNA appears to be stabilized. Although similar regulatory processes occur in response HgCl₂ vs. LPS, our data suggest that the translational processes (ATI) are differentially affected. In addition, a major difference lies in the fact that the C/EBPβ gene is not transcriptionally activated by HgCl₂. Our data show decreased binding activity and pool levels of the C/EBPα isoform (p42^C/EBPα) and increased binding activity and pool levels of C/EBPβ isoform (p35^C/EBPβ) in response to HgCl₂. We propose that this isoform may be involved in the regulation of AGP gene expression in response to heavy metals and that there is a significant difference between the HgCl₂-mediated and LPS-mediated inflammatory response.