PMID- 15570060 OWN - NLM STAT- MEDLINE DCOM- 20050113 LR - 20230216 IS - 0022-3166 (Print) IS - 0022-3166 (Linking) VI - 134 IP - 12 Suppl DP - 2004 Dec TI - Transcription factor Nrf2 is essential for induction of NAD(P)H:quinone oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates. PG - 3499S-3506S LID - 10.1093/jn/134.12.3499S [doi] AB - Cruciferous vegetables contain glucosinolates that, after conversion to isothiocyanates (ITC), are capable of inducing cytoprotective genes. We examined whether broccoli seeds can elicit a chemoprotective response in mouse organs and rodent cell lines and investigated whether this response requires nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). The seeds studied contained glucosinolate at 40 mmol/kg, of which 59% comprised glucoiberin, 19% sinigrin, 8% glucoraphanin, and 7% progoitrin. Dietary administration of broccoli seeds to nrf2(+/+) and nrf2(-/-) mice produced a approximately 1.5-fold increase in NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) activities in stomach, small intestine, and liver of wild-type mice but not in mutant mice; increased transferase activity was associated with elevated levels of GSTA1/2, GSTA3, and GSTM1/2 subunits. These seeds also increased significantly the level of glutamate cysteine ligase catalytic (GCLC) subunit in the stomach and the small intestine of nrf2(+/+) mice but not nrf2(-/-) mice. An aqueous broccoli seed extract was prepared for treatment of cultured cells that contained ITC at approximately 600 mumol/L, composed of 61% 3-methylsulfinylpropyl ITC, 30% sulforaphane, 4% allyl ITC, and 4% 3-butenyl ITC. This extract induced GSTA1/2, GSTA3, NQO1, and GCLC between 3-fold and 10-fold in mouse Hepa-1c1c7 and rat liver RL-34 cells. The broccoli seed extract affected increases in GSTA3, GSTM1, and NQO1 proteins in nrf2(+/+) mouse embryonic fibroblasts but not in nrf2(-/-) mouse embryonic fibroblasts. These experiments show that broccoli seeds are effective at inducing antioxidant and detoxication proteins, both in vivo and ex vivo, in an Nrf2-dependent manner. FAU - McWalter, Gail K AU - McWalter GK AD - Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom. FAU - Higgins, Larry G AU - Higgins LG FAU - McLellan, Lesley I AU - McLellan LI FAU - Henderson, Colin J AU - Henderson CJ FAU - Song, Lijiang AU - Song L FAU - Thornalley, Paul J AU - Thornalley PJ FAU - Itoh, Ken AU - Itoh K FAU - Yamamoto, Masayuki AU - Yamamoto M FAU - Hayes, John D AU - Hayes JD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Nutr JT - The Journal of nutrition JID - 0404243 RN - 0 (DNA-Binding Proteins) RN - 0 (Glucosinolates) RN - 0 (Isothiocyanates) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, mouse) RN - 0 (Plant Extracts) RN - 0 (Trans-Activators) RN - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone)) RN - EC 1.6.5.2 (NQO1 protein, human) RN - EC 2.5.1.18 (Glutathione Transferase) RN - EC 6.3.2.2 (Glutamate-Cysteine Ligase) SB - IM MH - Animals MH - Brassica/*chemistry MH - Cell Line MH - DNA-Binding Proteins/deficiency/genetics/*physiology MH - Diet MH - Enzyme Induction/drug effects MH - Gene Expression/drug effects MH - Glucosinolates/analysis/metabolism MH - Glutamate-Cysteine Ligase/*biosynthesis MH - Glutathione Transferase/*biosynthesis MH - Intestine, Small/enzymology MH - Isothiocyanates/administration & dosage/analysis/*pharmacology MH - Liver/enzymology MH - Mice MH - Mice, Knockout MH - Mutation MH - NAD(P)H Dehydrogenase (Quinone)/*biosynthesis MH - NF-E2-Related Factor 2 MH - Plant Extracts/chemistry/pharmacology MH - Seeds/chemistry MH - Stomach/enzymology MH - Trans-Activators/deficiency/genetics/*physiology MH - Transfection EDAT- 2004/12/01 09:00 MHDA- 2005/01/14 09:00 CRDT- 2004/12/01 09:00 PHST- 2004/12/01 09:00 [pubmed] PHST- 2005/01/14 09:00 [medline] PHST- 2004/12/01 09:00 [entrez] AID - S0022-3166(23)03199-1 [pii] AID - 10.1093/jn/134.12.3499S [doi] PST - ppublish SO - J Nutr. 2004 Dec;134(12 Suppl):3499S-3506S. doi: 10.1093/jn/134.12.3499S.