Hyppää sisältöön
    • FI
    • ENG
  • FI
  • /
  • EN
OuluREPO – Oulun yliopiston julkaisuarkisto / University of Oulu repository
Näytä viite 
  •   OuluREPO etusivu
  • Oulun yliopisto
  • Avoin saatavuus
  • Näytä viite
  •   OuluREPO etusivu
  • Oulun yliopisto
  • Avoin saatavuus
  • Näytä viite
JavaScript is disabled for your browser. Some features of this site may not work without it.

FoxO1 and HNF-4 are involved in regulation of hepatic glucokinase gene expression by resveratrol

Kumar Ganjam, Goutham; Dimova, Elitsa Y.; Unterman, Terry G.; Kietzmann, Thomas (2009-09-09)

 
Avaa tiedosto
nbnfi-fe201703152205.pdf (2.078Mt)
nbnfi-fe201703152205_meta.xml (34.21Kt)
nbnfi-fe201703152205_solr.xml (38.43Kt)
Lataukset: 

URL:
https://doi.org/10.1074/jbc.M109.045260

Kumar Ganjam, Goutham
Dimova, Elitsa Y.
Unterman, Terry G.
Kietzmann, Thomas
American Society for Biochemistry and Molecular Biology
09.09.2009

Goutham Kumar Ganjam, Elitsa Y. Dimova, Terry G. Unterman, Thomas Kietzmann (2009) FoxO1 and HNF-4 Are Involved in Regulation of Hepatic Glucokinase Gene Expression by Resveratrol. J. Biol. Chem. 2009 284: 30783-30797. doi:10.1074/jbc.M109.045260

https://rightsstatements.org/vocab/InC/1.0/
© 2009 by The American Society for Biochemistry and Molecular Biology, Inc. Published in this repository with the kind permission of the publisher.
https://rightsstatements.org/vocab/InC/1.0/
doi:https://doi.org/10.1074/jbc.M109.045260
Näytä kaikki kuvailutiedot
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi-fe201703152205
Tiivistelmä

Abstract

Resveratrol, a polyphenol derived from grapes, exerts important effects on glucose and lipid metabolism, yet detailed mechanisms mediating these effects remain unknown. The liver plays a central role in energy homeostasis, and glucokinase (GK) is a key enzyme involved in glucose utilization. Resveratrol activates SIRT1 (sirtuin 1), which promotes deacetylation of the forkhead transcription factor FoxO1. Previously, we reported that FoxO1 can suppress and that HNF-4 can stimulate GK expression in the liver. Here, we examined the role of FoxO1 and HNF-4 in mediating resveratrol effects on liver GK expression. Resveratrol suppressed hepatic GK expression in vivo and in isolated hepatocytes, and knocking down FoxO1 with shRNAs disrupted this effect. Reporter gene, gel shift, supershift assay, and chromatin immunoprecipitation studies show that FoxO1 binds to the GK promoter and that the interplay between FoxO1 and HNF-4 within the GK promoter is essential for mediating the effects of resveratrol. Resveratrol promotes deacetylation of FoxO1 and enhances its recruitment to the FoxO-binding element. Conversely, resveratrol suppresses recruitment of HNF-4 to its binding site, and knockdown of FoxO1 blocks this effect of resveratrol. Coprecipitation and chromatin immunoprecipitation studies show that resveratrol enhances interaction between FoxO1 and HNF-4, reduces binding of HNF-4 to its own site, and promotes its recruitment to the FoxO site in a FoxO1-dependent manner. These results provide the first evidence that resveratrol represses GK expression via FoxO1 and that the interaction between FoxO1 and HNF-4 contributes to these effects of resveratrol.

Kokoelmat
  • Avoin saatavuus [37606]
oulurepo@oulu.fiOulun yliopiston kirjastoOuluCRISLaturiMuuntaja
SaavutettavuusselosteTietosuojailmoitusYlläpidon kirjautuminen
 

Selaa kokoelmaa

NimekkeetTekijätJulkaisuajatAsiasanatUusimmatSivukartta

Omat tiedot

Kirjaudu sisäänRekisteröidy
oulurepo@oulu.fiOulun yliopiston kirjastoOuluCRISLaturiMuuntaja
SaavutettavuusselosteTietosuojailmoitusYlläpidon kirjautuminen