Fibroblast growth factor-10 attenuates H2O2-induced alveolar epithelial cell DNA damage: Role of MAPK activation and DNA repair

Daya Upadhyay, Michael Bundesmann, Vijayalakshmi Panduri, Eduardo Correa-Meyer, David W. Kamp*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Fibroblast growth factor-10 (FGF-10), an alveolar epithelial cell (AEC) mitogen that is critical for lung development, may promote AEC repair. We determined whether FGF-10 attenuates H2O2-induced, A549 and rat alveolar type II cell DNA damage. We show that FGF-10 prevents H 2O2-induced DNA damage assessed by an alkaline elution, ethidium bromide fluorescence as well as by a comet assay. Mitogen-activated protein kinase inhibitors abolished the protective effect of FGF-10 against H2O2-induced DNA damage yet had no effect on H 2O2-induced DNA damage. A Grb2-SOS inhibitor (SH3 binding peptide), an Ras inhibitor (farnesyl transferase inhibitor 277), and an Raf-1 inhibitor (forskolin) each prevented FGF-10- and H2O 2-induced A549 cell ERK1/2 phosphorylation. Also, FGF-10 and H 2O2 each induced negligible ERK1/2 phosphorylation in Ras dominant-negative (N17) cells. Inhibitors of Ras and Raf-1 blocked the protective effect of FGF-10 against H2O2-induced DNA damage but had no effect on H2O2-induced DNA damage. Furthermore, cold conditions and aphidicolin, an inhibitor of DNA polymerase-α, -δ, and -ε, each blocked the protective effects of FGF-10, suggesting a role for DNA repair. We conclude that FCF-10 attenuates H2O2-induced AEC DNA damage by mechanisms that involve activation of Grb2-SOS/Ras/RAF-1/ERK1/2 pathway and DNA repair.

Original languageEnglish (US)
Pages (from-to)107-113
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume31
Issue number1
DOIs
StatePublished - Jul 1 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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