The differential induction of α1-acid glycoprotein and serum amyloid A genes by heavy metals

Minas Yiangou, John Papaconstantinou

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

We have investigated the differential regulation of the mouse (Balb/c) acute phase reactants, α1-acid glycoprotein and serum amyloid A by heavy metals (Hg, Cd, Pb, Cu, Ni and Zn). Mice have two distinct α1-acid glycoprotein mRNAs encoded by α1-acid glycoprotein gene-1, (AGP-1) and ga1-acid glycoprotein gene-2 (AGP-2) and 3 distinct serum amyloid A mRNAs encoded by serum amyloid A gene-1, (SAA-1), serum amyloid A gene-2 (SAA-2) and serum amyloid A gene-3 (SAA-3). Using specific oligonucleotides as probes we have demonstrated that the AGP-1 and AGP-2 genes, and the SAA-1 and SAA-2 genes are differentially induced by heavy metals in the liver. At the peak of induction, AGP-2 mRNA is 80-100-fold higher than the AGP-1 mRNA level; the SAA-1 mRNA level is approx. 40-fold higher than SAA-2, and SAA-3 mRNA is not detected. A similar differential pattern of expression is observed in bacterial lipopolysaccharide mediated inductions. However, low levels of SAA-3 are also seen in this treatment. Adrenalectomy has no effect on the inductions by heavy metals of AGP-2 and the SAAs, indicating that the glucocorticoid receptor pathway may not function in this regulation. However, AGP-1 induction is significantly delayed, indicating that glucocorticoid may be essential for a rapid response to Hg. The liver is the major site of heavy metal induction of AGP and SAA genes; Hg induces AGP-1 and 2, and SAA-1 and 2 only in the liver. Our studies clearly show that the AGP and SAA genes belong to a subgroup of acute-phase reactants that respond to heavy metals. CRP is another member of this family. Furthermore, our data suggest that the mechanism is not directly mediated by glucocorticoid or cytokine induction pathways.

Original languageEnglish (US)
Pages (from-to)123-132
Number of pages10
JournalBBA - Gene Structure and Expression
Volume1174
Issue number2
DOIs
StatePublished - Aug 19 1993

Keywords

  • Alpha-1 acid glycoprotein
  • Gene regulation
  • Heavy metal
  • Serum amyloid A

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Genetics

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