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

• Published in: Helicobacter (Cambridge, Mass.) Mass.), 2020-10, Vol.25 (5), p.e12732-n/a
• Main Authors: Kawahara, Yoshinari, Hirashita, Yuka, Tamura, Chikako, Kudo, Yoko, Sakai, Kumiko, Togo, Kazumi, Fukuda, Kensuke, Matsunari, Osamu, Okamoto, Kazuhisa, Ogawa, Ryo, Mizukami, Kazuhiro, Okimoto, Tadayoshi, Kodama, Masaaki, Murakami, Kazunari
• Format: Article
• Language: English
• Subjects: Atrophy; Cancer; cytotoxin‐associated gene A; Discriminant analysis; Epithelial cells; Fluorescent indicators; Gas chromatography; Gastric cancer; Gastrointestinal system; Gastrointestinal tract; Helicobacter pylori; Hydrogen sulfide; Infections; Inoculation; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Metabolomics; Methionine; Mucosa; Production methods; Virulence; Virulence factors
• ISSN: 1083-4389; 1523-5378
• DOI: 10.1111/hel.12732

Background Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H2S), 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 H2S production. Materials and Methods 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 H2S levels were measured by using HSip‐1 fluorescent probe. Results 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 H2S production, was the most frequently altered pathway. H pylori‐inoculated cells produced more endogenous H2S than control cells. Moreover, ATCC 43504‐inoculated cells produced less H2S than ATCC 51932‐inoculated cells. Conclusions H pylori infection modulates endogenous H2S production in AGS cells, suggesting that H2S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy.