PMID- 20600030
OWN - NLM
STAT- MEDLINE
DCOM- 20101130
LR  - 20181201
IS  - 1528-0012 (Electronic)
IS  - 0016-5085 (Linking)
VI  - 139
IP  - 5
DP  - 2010 Nov
TI  - Coffee induces expression of glucuronosyltransferases by the aryl hydrocarbon 
      receptor and Nrf2 in liver and stomach.
PG  - 1699-710, 1710.e1-2
LID - 10.1053/j.gastro.2010.06.048 [doi]
AB  - BACKGROUND & AIMS: Coffee is one of the most widely consumed beverages worldwide. 
      Epidemiologic data indicate that coffee consumption protects against the 
      progression of chronic liver disease and development of hepatocellular carcinoma 
      and diabetes, but the mechanisms are not clear. UDP glucuronosyltransferases 
      (UGT1A) are proteins with indirect antioxidant, cytoprotective, and 
      genoprotective capabilities; we examined UGT1A regulation in response to coffee 
      in cultured cells and mice. METHODS: HepG2 and CaCo2 cells were incubated with 
      regular, metal- or paper-filtered, decaffeinated, or instant coffee; green or 
      black tea; cocoa; or metabolic products of caffeine. The effects of UGT1A 
      regulation were investigated with reporter gene assays, immunoblot, TaqMan 
      polymerase chain reaction, mutagenesis, and short interfering (si)RNA analyses. 
      We also studied the effects of coffee in humanized transgenic mice that express 
      human UGT1A. RESULTS: Incubation of cells with coffee induced transcription of 
      UGT1A1 (5.4-fold), UGT1A3 (5.2-fold), UGT1A4 (4.8-fold), UGT1A7 (6.2-fold), 
      UGT1A8 (5.2-fold), UGT1A9 (3.5-fold), and UGT1A10 (6.1-fold). Induction was 
      independent of caffeine, methylxanthines, or the diterpenes cafestol and kahweol. 
      Mutagenesis and short interfering RNA knockdown studies showed that UGT1A is 
      regulated by the aryl hydrocarbon receptor (AhR) and the nuclear factor 
      erythroid-related factor 2 (Nrf2) by cis-acting antioxidant and xenobiotic 
      response elements (ARE/XRE). In transgenic UGT1A mice, administration of coffee 
      resulted in a 10- and 14-fold induction of UGT1A transcription in liver and 
      stomach, respectively. CONCLUSIONS: UGT1A genes are induced in vitro and in vivo 
      by coffee, independent of caffeine content, cafestol, or kahweol. Coffee 
      up-regulates glucuronidation by AhR signaling and Nrf2 binding to the ARE/XRE. 
      Glucuronidation could mediate the protective and antioxidant effects of coffee.
CI  - Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
FAU - Kalthoff, Sandra
AU  - Kalthoff S
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Hannover, Germany.
FAU - Ehmer, Ursula
AU  - Ehmer U
FAU - Freiberg, Nicole
AU  - Freiberg N
FAU - Manns, Michael P
AU  - Manns MP
FAU - Strassburg, Christian P
AU  - Strassburg CP
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100620
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Coffee)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
SB  - IM
CIN - Gastroenterology. 2010 Nov;139(5):1453-7. PMID: 20875784
MH  - Animals
MH  - Blotting, Western
MH  - Chronic Disease
MH  - *Coffee
MH  - Disease Models, Animal
MH  - Female
MH  - Gastric Mucosa/*metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Glucuronosyltransferase/biosynthesis/*genetics
MH  - Humans
MH  - Liver/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Neoplasms/metabolism/pathology/prevention & control
MH  - RNA, Neoplasm/genetics
MH  - Receptors, Aryl Hydrocarbon/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stomach/pathology
MH  - Tumor Cells, Cultured
EDAT- 2010/07/06 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/07/06 06:00
PHST- 2009/12/30 00:00 [received]
PHST- 2010/05/12 00:00 [revised]
PHST- 2010/06/10 00:00 [accepted]
PHST- 2010/07/06 06:00 [entrez]
PHST- 2010/07/06 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - S0016-5085(10)00957-1 [pii]
AID - 10.1053/j.gastro.2010.06.048 [doi]
PST - ppublish
SO  - Gastroenterology. 2010 Nov;139(5):1699-710, 1710.e1-2. doi: 
      10.1053/j.gastro.2010.06.048. Epub 2010 Jun 20.