Geranylgeranylacetone protects guinea pig gastric mucosal cells from gastric stressor-induced necrosis by induction of heat-shock proteins.
Gastric mucosal cell death due to various gastric stressors can cause several types of gastric diseases, such as gastric ulcers. In this study, we examined cell death following the short-term treatment of guinea pig gastric mucosal cells in primary culture with various gastric stressors. The short-term treatment of cells with ethanol, hydrogen peroxide or hydrochloric acid caused, in a dose-dependent manner, cell death in the absence of apoptotic DNA fragmentation and chromatin condensation. Cells lost membrane integrity following the treatment with each of these gastric stressors, suggesting that necrosis was induced in gastric mucosal cells by short-term treatment of the cells with gastric stressors. Geranylgeranylacetone, an anti-ulcer drug with heat-shock protein inducing properties, protected gastric mucosal cells from the necrotic cell death caused by each of these gastric stressors. Pretreatment of cells with low concentrations of ethanol (3%), which also induced heat-shock protein, made cells resistant to the necrotic cell death caused by the gastric stressors. These results suggest that heat-shock proteins is involved in the cytoprotective effect of geranylgeranylacetone against necrotic cell death.
Tomisato
W
W
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Tsutsumi
S
S
Tsuchiya
T
T
Mizushima
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000473:pathology; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D006168:Guinea Pigs; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D015151:Immunoblotting; D008297:Male; D009336:Necrosis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D002843:Chromatin; D004224:Diterpenes; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C031049:geranylgeranylacetone