Aspirin-induced mucosal cell death in human gastric cells: evidence supporting an apoptotic mechanism.
This study was undertaken to define the role that apoptosis may play in inducing cellular injury and death in gastric mucosa exposed to aspirin. Apoptosis was characterized by DNA gel electrophoresis, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and DNA-histone-associated complex formation. A human gastric cell line (AGS) was exposed to physiologic concentrations (3 to 50 mM) of aspirin. Both time- and concentration-dependent effects on apoptosis were noted, which were effectively prevented by the caspase inhibitor z-VAD-fmk. Accordingly, the role of caspases in aspirin-induced apoptosis was also evaluated. Early activation of caspase-8 and caspase-9 was demonstrated, indicating a role for both receptor and mitochondrial pathways, respectively, in the apoptotic process. Corresponding activation of effector caspases-3, -6, and -7 was also evident, as was cleavage of PARP. We conclude that physiologically relevant concentrations of aspirin induces apoptosis in human gastric cells through a caspase-mediated mechanism.
Power
Jacinda J
JJ
Department of Surgery, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Dennis
Miranda S
MS
Redlak
Maria J
MJ
Miller
Thomas A
TA
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001241:Aspirin / Q000009:adverse effects* / Q000494:pharmacology*; D015153:Blotting, Western; D020169:Caspases / Q000032:analysis / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D020169:Caspases; D001241:Aspirin