Only live Helicobacter pylori is capable of caspase-3 dependent apoptosis induction in gastric mucosa epithelial cells.

Physiological process of cell death, apoptosis, plays a beneficial role in organism survival, but in some pathologies, like gastric Helicobacter pylori (Hp) infection, this process may turn against the host organism causing tissue damage. Knowledge of the mechanisms controlling apoptosis may have potential significance in treatment of these pathologic states. Therefore, we sought to determine whether apoptosis induced in the gastric epithelial cells exposed to live Hp involves the alteration in heat shock protein 70 (HSP70) expression and activation of caspase-3 in peroxisome proliferator-activated receptors (PPARgamma dependent manner). Experiments were performed with KATO III, gastric epithelial cells, exposed to CagA and Vac A positive live Hp, water Hp extracts or Hp culture supernatant over different time periods. Total cellular RNA and proteins were isolated for PCR, western-blot and EMSA studies. Genomic DNA was isolated to analyze apoptosis status. We propose new model of Hp induced HSP70 dependent, caspase-3 executed apoptosis in human gastric epithelium. KATO III cells exposed to Hp, showed an increase in caspase-3 activity accompanied and preceeded by activation of nuclear translocation of PPARg peaking at 48 h of culture. Moreover, heat shock factor 1 (HSF-1) bound up with phosphorylated STAT-3 was unable to activate HSP70 protein synthesis in KATO III exposed to Hp. Lack of protective effect of HSP70, activation of caspase-3--dependent apoptosis pathway caused by Hp and alteration of the bax/bcl-2 cellular equilibrium led to gastric epithelial cell death. The observed phenomenon might be helpful in understanding of the mechanism of Hp related gastrointestinal tract diseasess, especially gastric cancer.