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| Content Provider | PubMed Central |
|---|---|
| Author | Radin, Jana N. Christian, González-rivera Ivie, Susan E. Mcclain, Mark S. Cover, Timothy L. |
| Editor | Mccormick, B. A. |
| Copyright Year | 2011 |
| Abstract | Helicobacter pylori is a Gram-negative bacterium that colonizes the human stomach and contributes to the development of peptic ulcer disease and gastric cancer. The secreted pore-forming toxin VacA is one of the major virulence factors of H. pylori. In the current study, we show that AZ-521 human gastric epithelial cells are highly susceptible to VacA-induced cell death. Wild-type VacA causes death of these cells, whereas mutant VacA proteins defective in membrane channel formation do not. Incubation of AZ-521 cells with wild-type VacA results in cell swelling, poly(ADP-ribose) polymerase (PARP) activation, decreased intracellular ATP concentration, and lactate dehydrogenase (LDH) release. VacA-induced death of these cells is a caspase-independent process that results in cellular release of histone-binding protein high mobility group box 1 (HMGB1), a proinflammatory protein. These features are consistent with the occurrence of cell death through a programmed necrosis pathway and suggest that VacA can be included among the growing number of bacterial pore-forming toxins that induce cell death through programmed necrosis. We propose that VacA augments H. pylori-induced mucosal inflammation in the human stomach by causing programmed necrosis of gastric epithelial cells and subsequent release of proinflammatory proteins and may thereby contribute to the pathogenesis of gastric cancer and peptic ulceration. |
| Related Links | http://dx.doi.org/10.1128/iai.01370-10 |
| Ending Page | 2543 |
| Page Count | 9 |
| Starting Page | 2535 |
| File Format | |
| ISSN | 00199567 |
| e-ISSN | 10985522 |
| Journal | Infection and Immunity |
| Issue Number | 7 |
| Volume Number | 79 |
| Language | English |
| Publisher | American Society for Microbiology |
| Publisher Date | 2011-07-01 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology |
| Subject Keyword | Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Parasitology Immunology Microbiology |
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