Geranylgeranylacetone induces heat shock proteins in cultured guinea pig gastric mucosal cells and rat gastric mucosa.
OBJECTIVE
An antiulcer drug, geranylgeranylacetone (GGA), rapidly induces resistance of gastric mucosal cells to irritants in vivo and in vitro. The aim of this study was to elucidate the mechanism of this action.


METHODS
Heat shock proteins (HSPs) were detected by immunoblotting with antibody against HSP90, HSP70, heat shock cognate protein 70, or HSP60. HSP70 messenger RNA level was measured by Northern hybridization with an HSP70 complementary DNA probe. Activation of the heat shock factor was detected by gel mobility shift assay with the heat shock element oligonucleotide.


RESULTS
GGA induced resistance of cultured guinea pig gastric mucosal cells against ethanol-induced exfoliation and damage within 30 minutes, proportionally to the induction of the HSPs. This protection was blocked by cycloheximide but not by indomethacin. GGA caused rapid activation of heat shock factor 1 and expression of HSP70 messenger RNA in the cells. Intragastric administration of GGA to rats induced HSPs in gastric mucosa. The administration of GGA additionally enhanced the heat shock response and reduced ulcer formation in rats subjected to restraint and water-immersion stress.


CONCLUSIONS
GGA may induce transcriptional activation of HSP genes, and this novel action may increase gastric mucosal defense at conditions of stress.
Hirakawa
T
T
Department of Nutrition, School of Medicine, University of Tokushima, Japan.
Rokutan
K
K
Nikawa
T
T
Kishi
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D007101:Immersion / Q000503:physiopathology; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control; D013312:Stress, Physiological / Q000503:physiopathology; D015533:Transcriptional Activation
D000897:Anti-Ulcer Agents; D018834:Chaperonin 60; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; C031049:geranylgeranylacetone