Vulnerability of the human airway epithelium to hyperoxia

Constitutive expression of the catalase gene in human bronchial epithelial cells despite oxidant stress

Jee Hong Yoo, Serpil C. Erzurum, John G. Hay, Patricia Lemarchand, Ronald Crystal

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 "housekeeping" 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.

Original languageEnglish
Pages (from-to)297-302
Number of pages6
JournalJournal of Clinical Investigation
Volume93
Issue number1
Publication statusPublished - 1 Jan 1994
Externally publishedYes

Fingerprint

Hyperoxia
Oxidants
Catalase
Epithelium
Epithelial Cells
Gene Expression
5' Flanking Region
Genes
TATA Box
Cell Fusion
Transcription Initiation Site
Essential Genes
Base Composition
Heat-Shock Proteins
Luciferases
Reporter Genes
Transfection
Sequence Analysis
Cell Survival
Up-Regulation

Keywords

  • Adenovirus
  • Catalase
  • Gene expression
  • Gene transfer
  • Hyperoxia

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Vulnerability of the human airway epithelium to hyperoxia : Constitutive expression of the catalase gene in human bronchial epithelial cells despite oxidant stress. / Yoo, Jee Hong; Erzurum, Serpil C.; Hay, John G.; Lemarchand, Patricia; Crystal, Ronald.

In: Journal of Clinical Investigation, Vol. 93, No. 1, 01.01.1994, p. 297-302.

Research output: Contribution to journalArticle

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