title: Myrosinase-treated glucoerucin is a potent inducer of the Nrf2 target gene heme oxygenase 1--studies in cultured HT-29 cells and mice.
abstract: In this study, the effect of myrosinase-treated glucoerucin (GER+MYR), which releases the isothiocyanate (ITC) erucin, on heme oxygenase 1 (HO-1) gene expression and Nrf2 signaling was investigated in vitro in cultured cells and in vivo in mice. Treatment of HT-29 cells with GER+MYR resulted in a significant increase in the mRNA and protein levels of nuclear Nrf2 and HO-1. GER+MYR was more potent at enhancing the nuclear Nrf2 levels than were the following myrosinase-treated glucosinolates: sinigrin, glucoraphanin and gluconasturtiin, which are the precursors of allyl-ITC, R-sulforaphane and 2-phenylethyl ITC, respectively. GER+MYR also significantly induced HO-1 gene expression in the mouse intestinal mucosae and liver but not in the brain. Mechanistic studies suggest that GER+MYR induces Nrf2 via ERK1/2-, p38- and JNK-dependent signal transduction pathways. The GER+MYR-mediated increase in HO-1 expression is primarily attributable to p38 signaling.
authors.affiliation: Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany. Electronic address: wagner@molecularnutrition.uni-kiel.de.
authors.forename: Anika E
authors.initials: AE
authors.lastname: Wagner
authors.affiliation: Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany. Electronic address: sturm@foodsci.uni-kiel.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Sturm
authors.affiliation: Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany. Electronic address: piegholdt@foodsci.uni-kiel.de.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Piegholdt
authors.affiliation: Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany. Electronic address: i.wolf@uke.de.
authors.forename: Insa M A
authors.initials: IM
authors.lastname: Wolf
authors.affiliation: Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany. Electronic address: esatbeyoglu@foodsci.uni-kiel.de.
authors.forename: Tuba
authors.initials: T
authors.lastname: Esatbeyoglu
authors.affiliation: Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria, Centro di ricerca per le colture industriali, Via Di Corticella 133, Bologna 40128, Italy. Electronic address: ginarosalinda.denicola@entecra.it.
authors.forename: Gina Rosalinda
authors.initials: GR
authors.lastname: De Nicola
authors.affiliation: Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria, Centro di ricerca per le colture industriali, Via Di Corticella 133, Bologna 40128, Italy. Electronic address: renato.iori@entecra.it.
authors.forename: Renato
authors.initials: R
authors.lastname: Iori
authors.affiliation: Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany. Electronic address: rimbach@foodsci.uni-kiel.de.
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D005947:Glucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D005961:Glucosinolates / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000494:pharmacology; D019073:HT29 Cells; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007096:Imidoesters / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D017879:Isothiocyanates / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009149:Mustard Plant / Q000737:chemistry; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010091:Oximes; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013454:Sulfoxides; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D005961:Glucosinolates; D007096:Imidoesters; D017879:Isothiocyanates; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse; D010091:Oximes; D010936:Plant Extracts; D012333:RNA, Messenger; D013454:Sulfoxides; C443697:gluconasturtiin; C119493:glucoerucin; C010330:sinigrin; C058305:phenethyl isothiocyanate; C004471:allyl isothiocyanate; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D006026:Glycoside Hydrolases; C022739:thioglucosidase; C016766:sulforaphane; D005947:Glucose; C119494:glucoraphanin
keywords: Glucoerucin; Glucosinolates; Heme oxygenase 1; MAPK; Myrosinase; Nrf2