Oxygen Radical Induced Gastric Mucosal Cell Death: Apoptosis or Necrosis?

Reactive oxygen species (ROS) and resultant oxidative damage is a common pathway for gastric mucosal injury. This study was undertaken to determine whether apoptosis or necrosis was responsible for hydrogen peroxide (a representative ROS)-induced gastric mucosal death and whether caspase cascade blockade could prevent this process. AGS cells (human gastric adenocarcinoma cells) were exposed to hydrogen peroxide (H₂O₂), 0.5–2 mM, from 6 to 24 h. Lactic dehydrogenase (LDH) measured necrosis, whereas Caspase-3 and PARP activation and DNA-histone complex formation measured apoptosis. In addition, AGS cells received no pretreatment or preincubation for 1 h with 50–100 μM z-VAD, a pan-caspase inhibitor, and were then treated with 1–2 mM H₂O₂. With high concentrations of H₂O₂, cell death was predominantly necrotic, whereas lower concentrations evoked time and concentration dependent apoptosis. Furthermore, z-VAD pretreatment prevented oxidant induced apoptosis and necrosis. Since caspase cascade blockade prevents both processes, our results support the hypothesis that H₂O₂ induced cell death is predominantly a caspase-mediated apoptosis.