Resistance to apoptosis is a mechanism of adaptation of rat stomach to aspirin

Adaptation of the gastric mucosa to nonsteroidal anti-inflammatory drug-ind uced injury is a well-documented phenomenon, but the mechanisms are not kno wn. We investigated whether changes in stress protein expression and apopto sis play roles in adaptation of rat stomach to aspirin. RT-PCR and Western blotting techniques were used to analyze mRNA and protein expression of HSP 72 and HSP90 and cleavage of caspase 3 protein. Apoptosis was detected by t he TUNEL method and quantified. HSP72 mRNA and protein expression was uncha nged in adapted mucosa, whereas HSP90 mRNA and protein levels decreased. Ca spase 3 protein was activated, and the number of apoptotic cells increased in mucosa after one aspirin dose. However, in adapted mucosa after aspirin, activated caspase 3 and the number of apoptotic cells had returned to basa l levels. Induction of the stress response was found not to be a mechanism of mucosal adaptation against multiple doses of aspirin. Our results lead u s to propose instead that resistance to aspirin-induced apoptosis plays a r ole in the protective phenomenon of adaptation.