Regulation of heme oxygenase-1 expression in vivo and in vitro in hyperoxic lung injury. Academic Article uri icon

Overview

MeSH

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Epithelial Cells
  • Epithelium
  • Fibroblasts
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Immunohistochemistry
  • Kinetics
  • Lung Diseases
  • Macrophages, Alveolar
  • Macrophages, Peritoneal
  • Mice
  • Molecular Sequence Data
  • Oxygen
  • Protein Binding
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Specific Pathogen-Free Organisms
  • Transcription Factor AP-1
  • Transcription, Genetic

MeSH Major

  • Heme Oxygenase (Decyclizing)
  • Hyperoxia

abstract

  • Using hyperoxia as a model of oxidant-induced lung injury in the rat, we explored the regulation of heme oxygenase-1 (HO-1) expression in vivo and in vitro. We demonstrate marked increase of HO-1 messenger ribonucleic acid (mRNA) levels in rat lungs after hyperoxia. Increased HO-1 mRNA expression correlated with increased HO-1 protein and enzyme activity. Immunohistochemical studies of the rat lung after hyperoxia showed increased HO-1 expression in a variety of cell types, including the bronchoalveolar epithelium and interstitial and inflammatory cells. We then examined the regulation of HO-1 expression in vitro after hyperoxia and observed increased HO-1 gene expression in various cultured cells including epithelial cells, fibroblasts, macrophages, and smooth muscle cells. Increased HO-1 mRNA expression correlated with increased HO-1 protein in vitro, and resulted from increased gene transcription and not from increased mRNA stability. We show that transcriptional activation of the HO-1 gene by hyperoxia requires cooperation between the HO-1 promoter and an enhancer fragment located 4 kb upstream from its transcription site. Increased HO-1 gene transcription was associated with increased activator protein-1 (AP-1) binding activity and supershift of the AP-1 complex by antibodies to c-Fos and c-Jun after hyperoxia. Taken together, our data suggest that AP-1 activation may represent one mechanism mediating hyperoxia-induced HO-1 gene transcription.

publication date

  • June 1996

has subject area

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Epithelial Cells
  • Epithelium
  • Fibroblasts
  • Gene Expression Regulation, Enzymologic
  • Heme Oxygenase (Decyclizing)
  • Humans
  • Hyperoxia
  • Immunohistochemistry
  • Kinetics
  • Lung Diseases
  • Macrophages, Alveolar
  • Macrophages, Peritoneal
  • Mice
  • Molecular Sequence Data
  • Oxygen
  • Protein Binding
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Specific Pathogen-Free Organisms
  • Transcription Factor AP-1
  • Transcription, Genetic

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1165/ajrcmb.14.6.8652184

PubMed ID

  • 8652184

Additional Document Info

start page

  • 556

end page

  • 568

volume

  • 14

number

  • 6