Vulnerability of the human airway epithelium to hyperoxia. Constitutive expression of the catalase gene in human bronchial epithelial cells despite oxidant stress. Academic Article uri icon

Overview

MeSH

  • Base Sequence
  • Bronchi
  • Cell Line, Transformed
  • DNA
  • DNA Primers
  • Epithelium
  • Exons
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Introns
  • Luciferases
  • Molecular Sequence Data
  • RNA, Messenger
  • Transcription, Genetic
  • Transfection

MeSH Major

  • Catalase
  • Gene Expression
  • Oxygen

abstract

  • Although catalase is a major intracellular antioxidant, the expression of the human catalase gene appears to be limited in the airway epithelium, making these cells vulnerable to oxidant stress. The basis for this limited gene expression was examined by evaluation of the expression of the endogenous gene in human bronchial epithelial cells in response to hyperoxia. Hyperoxia failed to upregulate endogenous catalase gene expression, in contrast to a marked increase in expression of the heat shock protein gene. Sequence analysis of 1.7 kb of the 5'-flanking region of the human catalase gene showed features of a "house-keeping" gene (no TATA box, high GC content, multiple CCAAT boxes, and transcription start sites). Transfection of human bronchial epithelial cells with fusion genes composed of various lengths of the catalase 5'-flanking region and luciferase as a reporter gene showed low level constitutive promoter activity that did not change after exposure to hyperoxia. Importantly, using a replication-deficient recombinant adenoviral vector containing the human catalase cDNA, levels of catalase were significantly increased in human airway epithelial cells and this was associated with increased survival of the cells when exposed to hyperoxia. These observations provide a basis for understanding the sensitivity of the human airway epithelium to oxidant stress and a strategy for protecting the epithelium from such injury.

publication date

  • January 1994

has subject area

  • Base Sequence
  • Bronchi
  • Catalase
  • Cell Line, Transformed
  • DNA
  • DNA Primers
  • Epithelium
  • Exons
  • Gene Expression
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Introns
  • Luciferases
  • Molecular Sequence Data
  • Oxygen
  • RNA, Messenger
  • Transcription, Genetic
  • Transfection

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC293765

Digital Object Identifier (DOI)

  • 10.1172/JCI116959

PubMed ID

  • 8282800

Additional Document Info

start page

  • 297

end page

  • 302

volume

  • 93

number

  • 1