RRC ID 39760
著者 Shimada T, Hiraishi H, Terano A.
タイトル Hepatocyte growth factor protects gastric epithelial cells against ceramide-induced apoptosis through induction of cyclooxygenase-2.
ジャーナル Life Sci
Abstract Forced overexpression of cyclooxygenase-2 (COX-2) in intestinal cells has been shown to be associated with resistance to apoptosis. However, the role of physiologically-induced COX-2 in the regulation of apoptosis remains unclear. In the present study, we examined whether hepatocyte growth factor (HGF)-induced COX-2 affects ceramide-induced apoptosis in RGM-1 gastric epithelial cells. An externally applied cell permeable ceramide analogue, C2-ceramide, caused RGM-1 cell death in a dose-dependent manner, whereas an inactive ceramide analogue, C2-dihydroceramide, did not. TdT-mediated dUTP nick end labeling (TUNEL) assay showed that the C2-ceramide-induced cell death was apoptosis. Application of HGF rapidly induced the expression of COX-2, and HGF prevented the apoptotic cell death induced by C2-ceramide. However, the anti-apoptotic action of HGF was antagonized by coapplication of NS-398, a selective inhibitor of COX-2. Thus, these results indicate that COX-2 is involved in the survival signaling from HGF in gastric epithelial cells, and suggest a role for physiologically-induced COX-2 in the protection of the cells from apoptosis.
巻・号 68(5)
ページ 539-46
公開日 2000-12-22
DOI 10.1016/s0024-3205(00)00959-0
PII S0024320500009590
PMID 11197751
MeSH Animals Apoptosis / drug effects* Cell Line Cell Survival / drug effects Ceramides / pharmacology Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors / pharmacology Dose-Response Relationship, Drug Enzyme Induction / drug effects Gastric Mucosa / cytology Gastric Mucosa / drug effects* Gastric Mucosa / enzymology Hepatocyte Growth Factor / pharmacology* Humans In Situ Nick-End Labeling Isoenzymes / biosynthesis Isoenzymes / genetics* Membrane Proteins Nitrobenzenes / pharmacology Prostaglandin-Endoperoxide Synthases / biosynthesis Prostaglandin-Endoperoxide Synthases / genetics* RNA, Messenger / analysis Rats Recombinant Proteins / pharmacology Reverse Transcriptase Polymerase Chain Reaction Sphingosine / analogs & derivatives* Sphingosine / pharmacology* Sulfonamides / pharmacology Transcription, Genetic
IF 3.647
引用数 15
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 RGM1(RCB0876)