Abstract
The purpose of this study was to elucidate themolecular mechanism of action of geranylgeranylacetone,an antiulcer drug. Treatment with ethanol for 8 hr atthe optimum concentration (7.5%) caused apoptotic DNA fragmentation in cultured guinea piggastric mucosal cells. Pretreatment of cells withgeranylgeranylacetone suppressed the DNA fragmentationin a dose-dependent manner. The maximum effect wasachieved at 10-6 M, at which concentration the drug waspreviously shown to induce heat-shock proteins. Thesuppression required an incubation period longer than 1hr. Pretreatment of cells with low concentrations of ethanol also prevented DNAfragmentation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Murakami M, Oketani K, Fujisaki H, Wakabayashi T, Ohgo T: Antiulcer effect of geranylgeran ylacetone, a new acyclic polyisoprenoid on experimentally induced gastric and duodenalulcers in rats. Arzneimittelforschung 31:799-804, 1981
Fujimoto M, Yamanaka T, Bessho M, Igarashi T: Effects of geranylge ranylace tone on gastrointestinal secretion in rats. Eur J Pharmacol 77:113-118, 1982
Terano A, Shiga J, Hiraishi H, Ota S, Sugimoto T: Protective action of tetraprenylacetone against ethanol-induced damage in rat gastric mucosa. Digestion 35:182-188, 1986
Pappas TN, Mulvihill SJ, Goto Y, Debas HT: Advance s in drug Therapy for peptic ulcer disease. Arch Surg 122:447-450, 1987
Miller TA: Protective effects of prostaglandins against gastric mucosal damage: Current knowledge and proposed mechanisms. Am J Physiol 245:G601-G623, 1983
Terano A, Shiga J, Mutoh H, Hiraishi H, Shiina S, Kurita M, Ota S, Itoh Y, Sugimoto T: Protection against alcohol-induced gastric mucosal injury by geranylge ranylace tone: Effect of indomethacin. Dige stion 41:22-33, 1988
Bilski J, Murty VL, Nadzie jko C, Sarosiek J, Aono M, Moriga M, Slomiany A, Slomiany BL: Tetrapre nylace tone promote s healing proce ss of ethanol-induced gastric damage in The rat. Jpn J Pharmacol 55:115-120, 1991
Lindquist S: The heat-shock response. Annu Rev Biochem 55:1151-1191, 1986
Nakamura K, Rokutan K, Marui N, Aoike A, Kawai K: Induction of heat shock proteins and their implication in protection against ethanol-induced damage in cultured guinea pig gastric mucosal cells. Gastroenterology 101:161-166, 1991
Hirakawa T, Rokutan K, Nikawa T, Kishi K: Geranylgeranylacetone induces heat shock proteins in cultured guinea pig gastric mucosal cells and rat gastric mucosa. Gastroenterology 111:345-357, 1996
Mizushima T, Natori S, Sekimizu K: Relaxation of supercoiled DNA associated with induction of heat shock proteins in Escherichia coli. Mol Gen Gene t 238:1-5, 1993
Kane ko T, Mizushima T, Ohtsuka T, Kurokawa K, Kataoka K, Miki T, Sekimizu K: Co-induction of DNA relaxation and synthesis of DnaK and GroEL proteins in Escherichia coli by expression of LetD (CcdB) protein, an inhibitor of DNA gyrase encoded by the F factor. Mol Gen Genet 250:593-600, 1996
Mizushima T, Matsuo M, Sekimizu K: Induction of DnaK and GroEL proteins by fluoroquinolones in Escherichia coli. Antimicrob Agents ChemoTher 41:193-195, 1997
Kataoka K, Mizushima T, Ogata Y, Miki T, Sekimizu K: Heat shock-induced DNA relaxation in vitro by DNA gyrase of Esch erichiacoli in the pResence of ATP. J Biol Chem 271:24806-24810, 1996
Ogata Y, Mizushima T, Kataoka K, Kita K, Miki T, Sekimizu K: DnaK heat shock protein of Escherichia coli maintains the negative supercoiling of DNA against The rmal stRess. J Biol Chem 271:29407-29414, 1996
Higuchi H, Kurose I, Kato S, Miura S, Ishii H: Ethanolinduced apoptosis and oxidative stress in hepatocytes. Alcohol Clin Exp Res 20:340-346, 1996
Slukvin II, Jerrells TR: Different pathways of in vitro ethanolinduced apoptosis in thymocyte s and splenic T and B lymphocytes. Immunopharmacology 31:43-57, 1995
Rokutan K, Hirakawa T, Teshima S, Honda S, Kishi K: Glutathione depletion impairs transcriptional activation of heat shock genes in primary cultures of guinea pig gastric mucosal cells. Clin Invest 15:2242-2250, 1996
Robert A, Nezamis JE, Lancaste r C, Davis JP, Field SO, Hanchar AJ: Mild irritants prevent gastric necrosis through adaptive cytoprotection mediated by prostaglandins. Am J Physiol 245:G113-G121, 1983
Yajima N, Hiraishi H, Harada T: Protection of cultured rat gastric cells against oxidant stress by iron che lation. Role of lipid peroxidation. Dig Dis Sci 40:879-886, 1995
Rights and permissions
About this article
Cite this article
Mizushima, T., Tsutsumi, S., Rokutan, K. et al. Suppression of Ethanol-Induced Apoptotic DNA Fragmentation by Geranylgeranylacetone in Cultured Guinea Pig Gastric Mucosal Cells. Dig Dis Sci 44, 510–514 (1999). https://doi.org/10.1023/A:1026692920848
Issue Date:
DOI: https://doi.org/10.1023/A:1026692920848