Helicobacter pylori induces apoptosis in human epithelial gastric cells by stress activated protein kinase pathway.
BACKGROUND
The pathway by which Helicobacter pylori induces apoptosis in gastric epithelial cells is not known. The aim of this study was to determine whether H. pylori-induced apoptosis is associated with SAPK/JNK activity in human gastric cancer KATO III cells.


METHODS
H. pylori VacA toxin positive strain was incubated with KATO III cells for 0.5, 1, 2 or 24 hours. The SAPK/JNK protein was harvested from the KATO III cell lysate by precipitation with a C-jun fusion protein and its activity was measured by C-jun phosphorylation utilizing transblotting and phosphoserine antibody. Cellular apoptosis was demonstrated by DNA fragmentation. In addition, cell growth in coculture with H. pylori was determined over 72 hours.


RESULTS
H. pylori significantly stimulated SAPK/JNK activity in KATO III cells with a peak at the 0.5 hour time point (3.6-fold vs. control, p <.05), but a return to basal levels by 2 hours. In addition, significant DNA fragmentation was observed after 24 hours in these cells but not in the control KATO III cells. Cell growth was inhibited in a dose dependent fashion in coculture with H. pylori.


CONCLUSIONS
These results show that H. pylori triggers an increase in apoptosis in KATO III cells as reflected by DNA fragmentation. This effect was preceded and correlated with an increase in SAPK/JNK activity suggesting that the H. pylori-induced apoptosis in human gastric epithelial cells may be mediated by the SAPK/JNK pathway.
Domek
M J
MJ
VA Medical Center, Long Beach and the University of California, Irvine, CA, USA.
Netzer
P
P
Prins
B
B
Nguyen
T
T
Liang
D
D
Wyle
F A
FA
Warner
A
A
D017209:Apoptosis; D053938:DNA Fragmentation; D004847:Epithelial Cells / Q000382:microbiology*; D005753:Gastric Mucosa / Q000382:microbiology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D020928:Mitogen-Activated Protein Kinases