(2E,6Z,10E)-7-hydroxymethyl-3,11,15-trimethyl-2,6,10,14-hexadecatetraen-1-ol (Plaunotol) increases cyclooxygenase-2 expression via nuclear factor kappaB and cyclic AMP response element in rat gastric epithelial cells.
Plaunotol, [(2E,6Z,10E)-7-hydroxymethyl-3,11,15-trimethyl-2,6,10,14-hexadecatetraen-1-ol], a gastroprotective agent, increases the prostaglandin production in the gastric mucosa and accelerates ulcer healing. The precise mechanisms underlying the gastroprotective actions by plaunotol are not known. On the other hand, cyclooxygenase (COX)-2 is a key enzyme in PGE(2) production and its induction is thought to have an important role in ulcer healing. We investigated the mechanism of plaunotol-mediated COX-2 induction in rat gastric epithelial (RGM1) cells. We used a PGE(2) enzyme-linked immunoassay kit and Western blot analysis to measure PGE(2) production and COX-2 induction with plaunotol treatment in serum-starved RGM1 cells. In addition, gel-shift assay, Western blot analysis and a reporter assay were performed to observe which Cox-2 promoter was involved in plaunotol-induced Cox-2 expression. The findings indicated that plaunotol treatment dose-dependently increased COX-2 expression and PGE(2) production. The nuclear factor kappaB (NF-kappaB) and cyclic AMP response element (CRE) sites of the COX-2 gene promoter were critical to plaunotol-mediated COX-2 expression. In conclusion, plaunotol induced COX-2 expression and increased PGE(2) production in serum-starved RGM1 cells via activation of the NF-kappaB and CRE sites of Cox-2 gene promoters.
Fu
Hai ying
Hy
Department of Clinical Laboratory Science, School of Allied Heath Sciences, Osaka University Graduate School, Suita-City, Japan.
Yabe
Yuki
Y
Asahi
Kayoko
K
Hayashi
Yujiro
Y
Murata
Hiroaki
H
Eguchi
Hiroshi
H
Tsujii
Masahiko
M
Tsuji
Shingo
S
Kawano
Sunao
S
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005233:Fatty Alcohols / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000897:Anti-Ulcer Agents; D017362:Cyclic AMP Response Element-Binding Protein; D004224:Diterpenes; D005233:Fatty Alcohols; D016328:NF-kappa B; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins; D008156:Luciferases; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C047686:plaunotol