RRC ID 72955
Author Fujii Y, Matsura T, Kai M, Matsui H, Kawasaki H, Yamada K.
Title Mitochondrial cytochrome c release and caspase-3-like protease activation during indomethacin-induced apoptosis in rat gastric mucosal cells.
Journal Proc Soc Exp Biol Med
Abstract Indomethacin (IND), a nonsteroidal anti-inflammatory drug, has been known to cause gastric mucosal injury as a side effect. Using a rat gastric mucosal cell line, RGM1, we determined whether apoptosis is involved in IND-mediated gastropathy, and whether caspase activation and mitochondrial cytochrome c release play an important role in producing apoptosis of IND-treated RGM1 cells in the presence of serum. IND caused caspase-3-like protease activation followed by apoptosis in a dose- and time-dependent manner. Caspase-1-like protease activity did not change during IND-induced apoptosis. IND also increased mitochondrial cytochrome c release in a time-dependent fashion. Mitochondrial cytochrome c efflux occurred just before or at the same time as caspase-3-like protease activation, and preceded the increase in apoptotic cell numbers. Z-VAD-FMK, a caspase inhibitor, inhibited both the increase in caspase-3-like protease activity and apoptosis in IND-treated RGM1 cells but did not affect caspase-1-like protease activity or mitochondrial cytochrome c release. These observations suggest that the apoptosis of gastric mucosal cells could be involved in IND-induced gastropathy, that cytochrome c is released from mitochondria into the cytosol during the early phase of IND-mediated apoptosis, and that subsequent activation of caspase-3-like protease, but not caspase-1-like protease, is required for the execution of apoptosis.
Volume 224(2)
Pages 102-8
Published 2000-6-1
DOI 10.1046/j.1525-1373.2000.22407.x
PII pse22407
PMID 10806417
MeSH Amino Acid Chloromethyl Ketones / pharmacology Animals Anti-Inflammatory Agents, Non-Steroidal / metabolism* Anti-Inflammatory Agents, Non-Steroidal / pharmacology Caspase 3 Caspases / metabolism* Cell Line Cyclooxygenase Inhibitors / metabolism* Cyclooxygenase Inhibitors / pharmacology Cysteine Proteinase Inhibitors / pharmacology Cytochrome c Group / metabolism* Dose-Response Relationship, Drug Enzyme Activation Gastric Mucosa / cytology Indomethacin / metabolism* Indomethacin / pharmacology Mitochondria / drug effects Mitochondria / metabolism* Nitrobenzenes / pharmacology Peptide Hydrolases / metabolism Rats Sulfonamides / pharmacology Time Factors
Human and Animal Cells RGM1(RCB0876)