Apoptosis in the gastric mucosa: molecular mechanisms, basic and clinical implications.

Apoptosis a programmed cell death, is an essential mechanism of eliminating damaged or aged cells and thus to maintain tissue integrity. There are two central pathways that lead to apoptosis: a) the positive induction by ligands (death factors) binding to plasma membrane receptors (death factor receptors) and b) negative induction by the loss of suppressor activity. The common execution mechanisms of apoptosis consist of the activation of cytosolic aspartate-specific proteases (ICE-proteases) termed caspases, which can be activated via various intracellular pathways. In the stomach, mucosal surface epithelial cells are constantly exfoliating to the gastric lumen and completely replaced within 3-5 days under physiological conditions. Apoptosis has been reported to take place in all regions of the stomach with apoptotic cells occurring predominantly in the superficial parts of the gastric glands, at a rate of 2-3% for all cells. Following mucosal injury (e.g. ulcer development), apoptosis rapidly increases and remains elevated for 2-3 months. In a 3-month old ulcer scar, the apoptosis rate of mucous, parietal, chief and endocrine cells was found to be similar to that of normal gastric mucosa. Helicobacter pylori (H. pylori) infection induces apoptosis in the gastric mucosa and this action appears to be independent of VacA cytotoxin of H. pylori strains. Nonsteroidal anti-inflammatory drugs (NSAIDs), especially cyclooxygenase-2 (COX-2) inhibitors are potent inductors of gastric epithelial cell apoptosis. However, they can abrogate apoptosis or proliferation effects induced by H. pylori. Many details of the exact intracellular and molecular mechanisms regulating apoptosis in gastric mucosa remain to be elucidated.