Myrosinase-treated glucoerucin is a potent inducer of the Nrf2 target gene heme oxygenase 1--studies in cultured HT-29 cells and mice

Anika E Wagner; Christine Sturm; Stefanie Piegholdt; Insa M A Wolf; Tuba Esatbeyoglu; Gina Rosalinda De Nicola; Renato Iori; Gerald Rimbach

doi:10.1016/j.jnutbio.2015.01.004

Myrosinase-treated glucoerucin is a potent inducer of the Nrf2 target gene heme oxygenase 1--studies in cultured HT-29 cells and mice

J Nutr Biochem. 2015 Jun;26(6):661-6. doi: 10.1016/j.jnutbio.2015.01.004. Epub 2015 Mar 5.

Authors

Anika E Wagner¹, Christine Sturm², Stefanie Piegholdt³, Insa M A Wolf⁴, Tuba Esatbeyoglu⁵, Gina Rosalinda De Nicola⁶, Renato Iori⁷, Gerald Rimbach⁸

Affiliations

¹ Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany. Electronic address: wagner@molecularnutrition.uni-kiel.de.
² Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany. Electronic address: sturm@foodsci.uni-kiel.de.
³ Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany. Electronic address: piegholdt@foodsci.uni-kiel.de.
⁴ Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany. Electronic address: i.wolf@uke.de.
⁵ Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany. Electronic address: esatbeyoglu@foodsci.uni-kiel.de.
⁶ 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.
⁷ 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.
⁸ Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany. Electronic address: rimbach@foodsci.uni-kiel.de.

PMID: 25776458
DOI: 10.1016/j.jnutbio.2015.01.004

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.

Keywords: Glucoerucin; Glucosinolates; Heme oxygenase 1; MAPK; Myrosinase; Nrf2.

MeSH terms

Animals
Brain / drug effects
Brain / metabolism
Diet, High-Fat / adverse effects
Female
Glucose / analogs & derivatives*
Glucose / pharmacology
Glucosinolates / pharmacology
Glycoside Hydrolases / pharmacology
HT29 Cells
Heme Oxygenase-1 / genetics
Heme Oxygenase-1 / metabolism*
Humans
Imidoesters / pharmacology*
Intestinal Mucosa / metabolism
Intestines / drug effects
Isothiocyanates / metabolism
Liver / drug effects
Liver / metabolism
Membrane Proteins / genetics
Membrane Proteins / metabolism
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 3 / genetics
Mitogen-Activated Protein Kinase 3 / metabolism
Mustard Plant / chemistry
NF-E2-Related Factor 2 / genetics
NF-E2-Related Factor 2 / metabolism*
Oximes
Plant Extracts / pharmacology
RNA, Messenger / genetics
RNA, Messenger / metabolism
Signal Transduction
Sulfoxides
Up-Regulation
p38 Mitogen-Activated Protein Kinases / genetics
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Glucosinolates
Imidoesters
Isothiocyanates
Membrane Proteins
NF-E2-Related Factor 2
NFE2L2 protein, human
Nfe2l2 protein, mouse
Oximes
Plant Extracts
RNA, Messenger
Sulfoxides
gluconasturtiin
glucoerucin
sinigrin
phenethyl isothiocyanate
allyl isothiocyanate
HMOX1 protein, human
Heme Oxygenase-1
Hmox1 protein, mouse
Mitogen-Activated Protein Kinase 3
p38 Mitogen-Activated Protein Kinases
Glycoside Hydrolases
thioglucosidase
sulforaphane
Glucose
glucoraphanin