Spermine Oxidation Induced by Helicobacter pylori Results in Apoptosis and DNA Damage

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) H 2 O 2 is generated. Here, we report that H. pylori up-regulates mRNA expression, promoter activity, and enzyme activity of SMO (PAOh1)

Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis -induced colon tumorigenesis

“…1A). The magnitude and time course of stimulation of SMO transcription by BFT closely parallels that seen in response to H. pylori or TNF-α (21,22). In addition to induction of SMO at the gene expression level, BFT also similarly increased SMO protein levels (Fig.…”

“…Although inflammation-associated ROS has been implicated as one of the sources for the mutagens necessary to produce the genetic changes required for the carcinogenic process, the sources of the ROS have not been clearly identified. Whereas immune cells absolutely contribute to infection-associated tumorigenesis, this and other studies have demonsrated that bacteria can stimulate ROS production, cytokine secretion, DNA damage, and cellular proliferation in epithelial cells independent of any immune system contribution (5,9,17,22,37). SMO, a polyamine catabolic enzyme, is one such epithelial source of inflammation-induced ROS and DNA damage.…”

“…SMO is rapidly induced by the bacterial pathogen Helicobacter pylori and the pleiotropic mediator of inflammation, tumor necrosis factor-α (TNF-α), leading to SMO-dependent ROS production and DNA damage (21,22). Elevated SMO has also been observed in tissues from human inflammatory disease patients, including H. pyloriassociated gastritis, ulcerative colitis, prostatic intraepithelial neoplasia, and prostate cancer (22)(23)(24).ETBF-driven colonic tumorigenesis in the Min mouse therefore provides an ideal model in which to test the hypothesis that SMO induction is a fundamental molecular process directly linking inflammatory stimuli with carcinogenesis. This report summarizes experiments demonstrating that ETBF induces SMO expression in cell culture and animal models.…”

“…Recent reports suggest that a potential source of this inflammation-associated ROS production is the polyamine catabolic enzyme spermine oxidase (SMO), which generates H 2 O 2 as a byproduct of the back conversion of spermine to spermidine (19,20). SMO is rapidly induced by the bacterial pathogen Helicobacter pylori and the pleiotropic mediator of inflammation, tumor necrosis factor-α (TNF-α), leading to SMO-dependent ROS production and DNA damage (21,22). Elevated SMO has also been observed in tissues from human inflammatory disease patients, including H. pyloriassociated gastritis, ulcerative colitis, prostatic intraepithelial neoplasia, and prostate cancer (22)(23)(24).…”

Helicobacter pylori Induces ERK-dependent Formation of a Phospho-c-Fos·c-Jun Activator Protein-1 Complex That Causes Apoptosis in Macrophages

“…8F) when compared with H. pylori used as a positive control. We then added H. pylori strain 60190 to AGS gastric epithelial cells, using a defined model in which we have previously shown marked induction of apoptosis (44). However, even when assessed out to 240 min, there was no increase in pc-Fos levels when compared with unstimulated control cells, but there was an induction of c-Jun expression (Fig.…”