Geranylgeranylacetone protects guinea pig gastric mucosal cells from gastric stressor-induced apoptosis.
Various stressors induce apoptosis in gastric mucosal cells, which may cause gastric mucosal lesions in vivo. We recently reproduced gastric stressor-induced apoptosis in vitro, using primary cultures of guinea pig gastric mucosal cells. Geranylgeranylacetone is an antiulcer drug with heat-shock protein-inducing properties. The purpose of this study is to examine the effect of geranylgeranylacetone on gastric stressor-induced apoptosis in vitro. Ethanol, hydrogen peroxide, and hydrochloric acid all induced, in a dose-dependent manner, apoptotic DNA fragmentation. Pretreatment of cells with geranylgeranylacetone inhibited the apoptotic DNA fragmentation caused by each of these gastric stressors. Pretreatment of cells with a low concentration of ethanol, a procedure that is also known tb induce heat-shock proteins, made cells resistant to the apoptotic DNA fragmentation. These results suggest that heat-shock proteins could be at least partly involved in the inhibitory effect of geranylgeranylacetone against apoptosis of gastric mucosal cells caused by these gastric stressors.
Takano
Tatsunori
T
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-naka, Japan.
Tsutsumi
Shinji
S
Tomisato
Wataru
W
Hoshino
Tatsuya
T
Tsuchiya
Tomofusa
T
Mizushima
Tohru
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects*; D006168:Guinea Pigs; D006360:Heat-Shock Proteins / Q000502:physiology; D008297:Male; D013270:Stomach / Q000187:drug effects
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D006360:Heat-Shock Proteins; C031049:geranylgeranylacetone