Effects of mercuric chloride on the regulation of expression of the acute phase response components alpha(1)-acid glycoprotein and C/EBP transcription factors

We have previously shown that in response to treatment with HgCl2, the adul t mouse liver exhibits both transcriptional and translational regulation of the acute phase response genes. In this study we asked whether the heavy m etal treatment affects the regulation of the C/EBP transcription factors wh ich play a key role in regulation of the acute phase response gene. Our stu dies have shown that the AGP gene is transcriptionally activated while tran scription of the CCAAT/enhancer-binding trans-activating protein (C/EBP)alp ha gene is slightly down regulated and that of the C/EBP beta gene does not respond. Both the C/EBP alpha and C/EBP beta mRNAs produce multiple isofor ms possibly by alternative translation initiation (ATI) of multiple interna l AUG initiation sites. The C/EBP beta mRNA appears to be stabilized. Altho ugh similar regulatory processes occur in response HKCl2 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/EBP beta gene is not transcriptionally activated by HgCl2. Our data show decreased bindin g activity and pool levels of the C/EBP beta isoform (p42(C/EBP alpha)) and increased binding activity and pool levels of C/EBP beta isoform (p35(C/EB P beta)) 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 t hat there is a significant difference between the HgCl2-mediated and LPS-me diated inflammatory response. (C) 2001 Elsevier Science B.V. All rights res erved.