Abstract
Mice fed diets containing 3% or 6% coffee for 5 days had increased levels of mRNA for NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase class Alpha 1 (GSTA1) of between 4- and 20-fold in the liver and small intestine. Mice fed 6% coffee also had increased amounts of mRNA for UDP-glucuronosyl transferase 1A6 (UGT1A6) and the glutamate cysteine ligase catalytic (GCLC) subunit of between 3- and 10-fold in the small intestine. Up-regulation of these mRNAs was significantly greater in mice possessing Nrf2 (NF-E2 p45 subunit-related factor 2) than those lacking the transcription factor. Basal levels of mRNAs for NQO1, GSTA1, UGT1A6 and GCLC were lower in tissues from nrf2(-/-) mice than from nrf2(+/+) mice, but modest induction occurred in the mutant animals. Treatment of mouse embryonic fibroblasts (MEFs) from nrf2(+/+) mice with either coffee or the coffee-specific diterpenes cafestol and kahweol (C + K) increased NQO1 mRNA up to 9-fold. MEFs from nrf2(-/-) mice expressed less NQO1 mRNA than did wild-type MEFs, but NQO1 was induced modestly by coffee or C + K in the mutant fibroblasts. Transfection of MEFs with nqo1-luciferase reporter constructs showed that induction by C + K was mediated primarily by Nrf2 and required the presence of an antioxidant response element in the 5'-upstream region of the gene. Luciferase reporter activity did not increase following treatment of MEFs with 100 mu mol/l furan, suggesting that this ring structure within C + K is insufficient for gene induction. Priming of nrf2(+/+) MEFs, but not nrf2(-/-) MEFs, with C + K conferred 2-fold resistance towards acrolein. (c) 2007 Elsevier Inc. All rights reserved.
Original language | English |
---|---|
Pages (from-to) | 328-337 |
Number of pages | 10 |
Journal | Toxicology and Applied Pharmacology |
Volume | 226 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Feb 2008 |
Keywords
- antioxidant response element
- arylhydrocarbon receptor
- glutathione S-transferase
- NAD(P)H : quinone oxidoreductase 1
- Nrf2
- GLUTATHIONE-S-TRANSFERASE
- ANTIOXIDANT RESPONSE ELEMENT
- ARYL-HYDROCARBON RECEPTOR
- GLUTAMATE-CYSTEINE LIGASE
- INDUCIBLE EXPRESSION
- CONSENSUS SEQUENCE
- GENE-EXPRESSION
- LEUCINE-ZIPPER
- NAD(P)H-QUINONE OXIDOREDUCTASE-1
- BUTYLATED HYDROXYANISOLE