Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: Implications for gastric carcinogenesis

Hangxiu Xu, Rupesh Chaturvedi, Yulan Cheng, Francoise I. Bussiere, Mohammad Asim, Micheal D. Yao, Darryn Potosky, Stephen J. Meltzer, Juong G. Rhee, Sung S. Kim, Steven F. Moss, Amy Hacker, Yanlin Wang, Robert A. Casero, Keith T. Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

Oxidative stress is linked to carcinogenesis due to its ability to damage DNA. The human gastric pathogen Helicobacter pylori exerts much of its pathogenicity by inducing apoptosis and DNA damage in host gastric epithelial cells. Polyamines are abundant in epithelial cells, and when oxidized by the inducible spermine oxidase SMO(PAOh1) H2O2 is generated. Here, we report that H. pylori up-regulates mRNA expression, promoter activity, and enzyme activity of SMO(PAOh1) in human gastric epithelial cells, resulting in DNA damage and apoptosis. H. pylori-induced H2O2 generation and apoptosis in these cells was equally attenuated by an inhibitor of SMO(PAOh1), by catalase, and by transient transfection with small interfering RNA targeting SMO(PAOh1). Conversely, SMO(PAOh1) overexpression induced apoptosis to the same levels as caused by H. pylori. Importantly, in H. pylori-infected tissues, there was increased expression of SMO(PAOh1) in both human and mouse gastritis. Laser capture microdissection of human gastric epithelial cells demonstrated expression of SMO(PAOh1) that was significantly attenuated by H. pylori eradication. These results identify a pathway for oxidative stress-induced epithelial cell apoptosis and DNA damage due to SMO(PAOh1) activation by H. pylori that may contribute to the pathogenesis of the infection and development of gastric cancer.

Original languageEnglish (US)
Pages (from-to)8521-8525
Number of pages5
JournalCancer Research
Volume64
Issue number23
DOIs
StatePublished - Dec 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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