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.
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-naka, Japan.
Tatsunori
T
Takano
Shinji
S
Tsutsumi
Wataru
W
Tomisato
Tatsuya
T
Hoshino
Tomofusa
T
Tsuchiya
Tohru
T
Mizushima
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