Structure and negative transcriptional regulation by glucocorticoids of the acute-phase rat alpha 1-inhibitor III gene

Biochemistry. 1989 Jan 10;28(1):84-95. doi: 10.1021/bi00427a013.

Abstract

DNA clones representing the negative acute-phase gene coding for the plasma proteinase inhibitor alpha 1-inhibitor III were isolated from a rat genomic library. Structural analysis established the existence of at least four different members of the alpha 1-inhibitor III gene family. Partial DNA sequence analysis of the 5'-terminal regions was performed for the alpha 1-inhibitor III gene and the related alpha 1-inhibitor IV gene. The transcription start site of the alpha 1-inhibitor III gene was located by S1 mapping and primer extension. No stable alpha 1-inhibitor IV mRNA was detected in rat liver. In an experimentally induced acute-phase reaction, the transcription rate of the alpha 1-inhibitor III gene was reduced 12.7-fold at 6 h after stimulation. Four hours after injection of a high dose of dexamethasone into rats, the transcription rate of this gene was reduced 9-fold. Thus, glucocorticoids alone are capable of causing a strong transient down-regulation of the transcription of this gene in rats, independent of other inflammatory mediators. An inverted consensus glucocorticoid responsive element (5'GGACACAATAT3') shared with the glucocorticoid-regulated alpha 1-fetoprotein, alpha 2u-globulin, and alpha 1-acid glycoprotein genes was detected by computer-assisted sequence analysis in the promoter proximal 5'-flanking region of the alpha 1-inhibitor III gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute-Phase Proteins*
  • Acute-Phase Reaction / genetics
  • Animals
  • Base Sequence
  • DNA / genetics
  • Dexamethasone / pharmacology*
  • Male
  • Molecular Sequence Data
  • Multigene Family
  • Protease Inhibitors / genetics*
  • Rats
  • Rats, Inbred F344
  • Restriction Mapping
  • Sequence Homology, Nucleic Acid
  • Transcription, Genetic / drug effects*

Substances

  • Acute-Phase Proteins
  • Protease Inhibitors
  • alpha 1-inhibitor 3
  • Dexamethasone
  • DNA

Associated data

  • GENBANK/J03552
  • GENBANK/M22993
  • GENBANK/M22994