title: Geranylgeranylacetone induces cyclooxygenase-2 expression in cultured rat gastric epithelial cells through NF-kappaB.
abstract: Geranylgeranylacetone (GGA) effectively protects the gastric mucosa against noxious agents. The precise mechanisms underlying the gastroprotective actions of GGA are not known. To elucidate the precise mechanism of GGA, the effect of GGA treatment on COX-2 expression in rat gastric epithelial (RGM1) cells was investigated. We used a prostaglandin E2 (PGE2) enzyme-linked immunoassay kit and Western blot analysis to measure PGE2 production and COX-2 induction by GGA treatment in serum-starved RGM1 cells. Gel-shift assay, Western blot analysis, and a reporter assay were performed to determine which COX-2 promoter was involved in GGA-induced COX-2 expression. GGA treatment dose dependently increased COX-2 expression and PGE2 production. The nuclear factor (NF)-kappaB sites of the COX-2 gene promoter were critical for GGA-mediated COX-2 expression. GGA induces COX-2 expression and increases PGE2 production in serum-starved RGM1 cells via activation of the NF-kappaB sites of COX-2 gene promoters.
authors.affiliation: Department of Clinical Laboratory Science, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Osaka, Japan. tnishida@gh.med.osaka-u.ac.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nishida
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yabe
authors.forename: Hai Ying
authors.initials: HY
authors.lastname: Fu
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Kayoko
authors.initials: K
authors.lastname: Asahi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Shingo
authors.initials: S
authors.lastname: Tsuji
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsujii
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.forename: Sunao
authors.initials: S
authors.lastname: Kawano
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000032:analysis; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000032:analysis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D008565:Membrane Proteins / Q000032:analysis; D016328:NF-kappa B / Q000032:analysis; D051381:Rats
chemical_list: D000897:Anti-Ulcer Agents; D022782:CCAAT-Enhancer-Binding Protein-beta; D004224:Diterpenes; D008565:Membrane Proteins; D016328:NF-kappa B; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; D015232:Dinoprostone; C031049:geranylgeranylacetone