Ammonia as an Accelerator of Tumor Necrosis Factor Alpha-Induced Apoptosis of Gastric Epithelial Cells in Helicobacter pylori Infection

Abstract

The mechanism by which Helicobacter pylori induces apoptosis remains unclear. In a previous study using biopsy samples, we found a significant correlation between the urease activity of an H. pylori strain and the apoptosis level induced by this strain. Therefore, in this study, we investigated whether urease and/or the ammonia generated by urease can induce apoptosis. Human gastric epithelial cell lines were cocultured with H. pylori, and the levels of apoptosis and ammonia production were measured. The medium was supplemented (or not supplemented) with urea and cytokines. While a large amount of ammonia (>30 mM) accumulated in the coculture containing urease-positive H. pylori and urea, no significant degree of apoptosis occurred. In the presence of tumor necrosis factor alpha (TNF-␣), however, a marked acceleration of apoptosis was found in this coculture. Such enhancement of apoptosis was also induced by the addition of 4 to 8 mM ammonia to the cell culture without either H. pylori or urea but containing TNF-␣. These results suggested that ammonia accelerates cytokine-induced apoptosis in gastric epithelial cells, while ammonia or urease molecules alone are unable to induce a significant degree of apoptosis.

Relationship between ureB Sequence Diversity, Urease Activity and Genotypic Variations of Different Helicobacter pylori Strains in Patients with Gastric Disorders

“…The association between urease activity and peptic ulcer was described by several studies. It seems that ammonia produced by the urease can induce apoptosis, whose action promotes tissue damage and ulcer formation (Igarashi et al, 2001). Although there is no report about higher level of urease activity in patients with peptic ulcer, the increased activity was previously established in strains from cancer patients (Ito et al, 1995).…”

Growth Phase-Dependent Response ofHelicobacter pylorito Iron Starvation

“…As a group, bacterial amidases catalyze the hydrolysis of short-chain aliphatic amides to ammonia and the corresponding organic acid and play a valuable role in nitrogen metabolism (55). This is particularly true in H. pylori since ammonia not only is the preferred source of nitrogen for the synthesis of amino acids, pyrimidines, and purines but also contributes to epithelial cell damage and chemotactic motility and is a crucial component of the acid resistance pathway for the bacterium (30,40,50,71). Previous characterization of the AmiE and AmiF amidases has indicated that they show marked substrate specificity and that their activity is dependent on the activities of other enzymes of the nitrogen metabolism pathways of H. pylori, namely, those of urease and arginase (55).…”

Effect ofHelicobacter pyloriinfection on expressions of Bcl-2 family members in gastric adenocarcinoma

“…The role of H pylori infection in the gastric carcinogenesis is not clear. It might be involved in imbalance between apoptosis and proliferation [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] . Bcl-2 family members have been closely related to apoptosis, which could either promote cell survival (Bcl-2, Bcl-x L , A1, Mcl-1, and Bcl-w) or promote cell death (Bax, Bak, Bcl-x S , Bad, Bid, Bik, Bim, Hrk, Bok) [34][35][36] .…”