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N ‐methyl‐D‐aspartate (NMDA) Channels Regulate Apoptosis in Helicobacter pylori infection by Ammonia‐induced Calcium Permeation Mechanisms
Author(s) -
Seo Ji Hye,
Fox James G,
Peek Richard M,
Hagen Susan J
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1156.1
Subject(s) - nmda receptor , apoptosis , calcium , viability assay , chemistry , cell , microbiology and biotechnology , transfection , biology , biochemistry , receptor , gene , organic chemistry
Background Mechanisms that regulate epithelial cell apoptosis in Helicobacter pylori (HP) infection are not well understood. We tested whether ammonia, which is an important cytotoxin produced by HP, increases cell apoptosis by activating N ‐methyl‐ d ‐aspartate (NMDA) channels, which are calcium‐influx channels. Methods MKN28 cells were transfected with a control or NMDA receptor 2B expression plasmid, creating NR2B+ and NR2B‐ cells. Each cell type was incubated with the wild‐type (WT) cag + toxigenic HP strain 60190 or its isogenic ure B (uB) mutant, which does not produce ammonia. Calcium permeation and cell viability were tested. Results NR2B+ cells incubated with WT HP showed extensive calcium permeation and reduced cell viability that did not occur with uB. Additionally, NR2B+, but not NR2B‐, cells transcriptionally up‐regulated NR2B in the presence of WT but not uB. The surface epithelium from HP‐infected mice also showed a highly significant up‐regulation of NMDA channel expression. Conclusion Our results show that ammonia produced by WT HP transcriptionally up‐regulates NMDA channels to facilitate calcium influx, which significantly reduces cell viability. These results suggest that NMDA channels may be essential to modulate apoptosis pathways during HP infection‐mediated cancer development. This work was supported by NIH DK015681 and by Departmental funding.