Helicobacter pylori and H2O2 increase AP endonuclease-1/redox factor-1 expression in human gastric epithelial cells.
BACKGROUND & AIMS: Helicobacter pylori infection causes inflammation, accumulation of reactive oxygen species, and oxidative DNA damage in the gastric mucosa. Apurinic/apyrimidinic endonuclease-1 (APE-1)/redox factor-1 (Ref-1) repairs damaged DNA and reductively activates transcription factors, including activator protein-1. Considering that H. pylori generate reactive oxygen species and that reactive oxygen species modulate APE-1/Ref-1 in other cell types, we examined the effect of H. pylori, oxidative stress, and antioxidants on APE-1/Ref-1 expression in human gastric epithelial cells. METHODS: Human gastric epithelial cell lines or cells isolated from mucosal biopsy samples were stimulated with H. pylori, Campylobacter jejuni, and/or H 2 O 2 in the presence or absence of antioxidants. APE-1/Ref-1 expression was assayed by Western blot or reverse-transcription polymerase chain reaction, and its cellular distribution was determined by using indirect conventional and confocal immunofluorescence. New protein synthesis was detected by [S 35 ]methionine labeling. APE-1/Ref-1 function was assessed by using a luciferase- linked reporter construct containing 3 activator protein 1 binding sites. RESULTS: APE-1/Ref-1 protein and messenger RNA were detected in resting gastric epithelial cells. APE-1/Ref-1 protein expression was increased after stimulation with H 2 O 2 or live cag pathogenicity island-bearing H. pylori, but not cag pathogenicity island-negative H. pylori or C. jejuni. H. pylori - or reactive oxygen species-mediated increases in APE-1/Ref-1 expression involved de novo protein synthesis that was inhibited by antioxidants. H. pylori or H 2 O 2 also induced nuclear accumulation of APE-1/Ref-1, and overexpression of APE-1/Ref-1 increased activator protein 1 binding activity. CONCLUSIONS: The data show that H. pylori or reactive oxygen species enhance APE-1/Ref-1 protein synthesis and nuclear accumulation in human gastric epithelial cells and implicate APE-1/Ref-1 in the modulation of the pathogenesis of H. pylori infection.[1]References
- Helicobacter pylori and H2O2 increase AP endonuclease-1/redox factor-1 expression in human gastric epithelial cells. Ding, S.Z., O'Hara, A.M., Denning, T.L., Dirden-Kramer, B., Mifflin, R.C., Reyes, V.E., Ryan, K.A., Elliott, S.N., Izumi, T., Boldogh, I., Mitra, S., Ernst, P.B., Crowe, S.E. Gastroenterology (2004) [Pubmed]
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