Helicobacter pylori infection modulates endogenous hydrogen sulfide production in gastric cancer AGS cells

Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H2 S), a gaseous biological transmitter, has been implicated in both the physiological functions of the gastrointestinal tract and its diseases. To understand gastric epithelial cell response against H pylori infection, we investigated the metabolic changes of gastric cancer cells co-cultured with H pylori and observed the modulation of endogenous H2 S production. Materials and

H pylori infection modulates endogenous H2 S production in AGS cells, suggesting that H2 S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy.

Gastric cancer AGS cells were co-cultured with an H pylori standard strain possessing bacterial virulence factor CagA (ATCC 43504) and a strain without CagA (ATCC 51932). Three hours after inoculation, the cells were subjected to metabolomics analysis using gas chromatography-tandem mass spectrometry (GC-MS/MS). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and pathway analysis were performed. In addition, intracellular H2 S levels were measured by using HSip-1 fluorescent probe.

Results of OPLS-DA showed a significant difference between the metabolism of untreated control cells and cells inoculated with the H pylori strains ATCC 51932 or ATCC 43504, mainly due to 45 metabolites. Pathway analysis with the selected metabolites indicated that methionine metabolism, which is related to H2 S production, was the most frequently altered pathway. H pylori-inoculated cells produced more endogenous H2 S than control cells. Moreover, ATCC 43504-inoculated cells produced less H2 S than ATCC 51932-inoculated cells. Conclusions: H pylori infection modulates endogenous H2 S production in AGS cells, suggesting that H2 S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy.