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 (H(2)O(2)), 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 microM z-VAD, a pan-caspase inhibitor, and were then treated with 1-2 mM H(2)O(2). With high concentrations of H(2)O(2), 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 H(2)O(2) induced cell death is predominantly a caspase-mediated apoptosis.
Leung
Anna M
AM
Department of Surgery, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0568, USA.
Redlak
Maria J
MJ
Miller
Thomas A
TA
D000230:Adenocarcinoma / Q000473:pathology; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009336:Necrosis; D009842:Oligopeptides / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013274:Stomach Neoplasms / Q000473:pathology
D009842:Oligopeptides; D016877:Oxidants; D017382:Reactive Oxygen Species; C103712:benzyloxycarbonyl-valyl-alanyl-aspartyl-fluoromethane; D006861:Hydrogen Peroxide; D053148:Caspase 3