Protection of human lung cells against hyperoxia using the DNA base excision repair genes hOgg1 and Fpg

Min Wu, Ying Hui He, Masayoshi Kobune, Yi Xu, Mark R. Kelley, William J. Martin

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Hyperoxia causes pulmonary toxicity in part by injuring alveolar epithelial cells. Previous studies have shown that toxic oxygen-derived species damage DNA and this damage is recognized and repaired by either human enzyme 8-oxoguanine DNA glycosylase (hOgg1) or Escherichia coli enzyme formamidopyrimidine DNA glycosylase (Fpg). To determine whether these DNA repair proteins can reduce O2-mediated DNA damage in lung cells, A549 lung epithelial cells were transduced with either hOgg1 or Fpg using a retroviral vector containing enhanced green fluorescent protein. Expression of each gene in the transduced cells was confirmed by fluorescent microscopy, Northern blotting, Western blotting, and an enzymatic oligonucleotide cleavage assay. A549 cells expressing either hOgg1 or Fpg were protected from hyperoxia as evidenced by a decrease in DNA damage and a corresponding increase in cell survival. Further, we determined that overexpression of hOgg1 or Fpg partially mitigated the toxic effects of hydrogen peroxide in lung cells. Our data suggest that increased expression of DNA base excision repair genes might represent a new approach for protecting critical lung cells from the toxic effects of hyperoxia.

Original languageEnglish (US)
Pages (from-to)192-199
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Volume166
Issue number2
DOIs
StatePublished - Jul 15 2002

Fingerprint

DNA-Formamidopyrimidine Glycosylase
Hyperoxia
DNA Repair
Poisons
Lung
DNA
DNA Damage
Genes
Alveolar Epithelial Cells
Enzymes
Oligonucleotides
Northern Blotting
Hydrogen Peroxide
Microscopy
Cell Survival
Western Blotting
Epithelial Cells
Oxygen
Escherichia coli
Gene Expression

Keywords

  • DNA damage
  • DNA repair
  • Hydrogen peroxide
  • Oxygen toxicity

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Protection of human lung cells against hyperoxia using the DNA base excision repair genes hOgg1 and Fpg. / Wu, Min; He, Ying Hui; Kobune, Masayoshi; Xu, Yi; Kelley, Mark R.; Martin, William J.

In: American journal of respiratory and critical care medicine, Vol. 166, No. 2, 15.07.2002, p. 192-199.

Research output: Contribution to journalArticle

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