Resistance to apoptosis is a mechanism of adaptation of rat stomach to aspirin.
Adaptation of the gastric mucosa to nonsteroidal anti-inflammatory drug-induced injury is a well-documented phenomenon, but the mechanisms are not known. We investigated whether changes in stress protein expression and apoptosis play roles in adaptation of rat stomach to aspirin. RT-PCR and Western blotting techniques were used to analyze mRNA and protein expression of HSP72 and HSP90 and cleavage of caspase 3 protein. Apoptosis was detected by the TUNEL method and quantified. HSP72 mRNA and protein expression was unchanged in adapted mucosa, whereas HSP90 mRNA and protein levels decreased. Caspase 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 basal levels. Induction of the stress response was found not to be a mechanism of mucosal adaptation against multiple doses of aspirin. Our results lead us to propose instead that resistance to aspirin-induced apoptosis plays a role in the protective phenomenon of adaptation.
Alderman
B M
BM
University of Melbourne, Department of Medicine, Western Hospital, Footscray, Victoria 3011, Australia.
Cook
G A
GA
Familari
M
M
Yeomans
N D
ND
Giraud
A S
AS
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology*; D001241:Aspirin / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000187:drug effects* / Q000503:physiopathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D001241:Aspirin