title: Induction of hepatic apolipoprotein A-I gene expression by the isoflavones quercetin and isoquercetrin.
abstract: OBJECTIVE
  Phytochemicals such as flavonoids, vitamins, and polyphenols have been shown to have beneficial effects in metabolic disease. To determine if select flavonoids regulate hepatic apolipoprotein A-I (apo A-I) and high-density lipoprotein (HDL) synthesis, we examined the effects of quercetin, isoquercetin, and myrescetin on apo A-I gene expression in HepG2 (hepatocytes) and Caco-2 (intestinal) cells.
  
  
  METHODS
  Apo A-I gene expression was measured by Western blotting, quantitative reverse-transcription polymerase chain reaction, and transient transfection. Estrogen receptor α (ESR1) and estrogen receptor β expression were measured by Western blotting, and ESR1 expression was inhibited using ESR1-specific short inhibitory RNA (siRNA).
  
  
  RESULTS
  Quercetin and isoquercetin, but not myrecetin, induced apo A-I protein and mRNA synthesis, and induced apo A-I promoter activity. Induction by quercetin required an estrogen-responsive region of the apo A-I promoter. Addition of estrogen receptor blocker ICI-182780 to quercetin-treated cells inhibited the effects of quercetin on apo A-I gene expression. Down-regulation of ESR1 with ESR1 siRNA had no effect on basal apo A-I gene expression; however it prevented quercetin-mediated induction of apo A-I gene expression.
  
  
  CONCLUSIONS
  We conclude that quercetin induces apo A-I gene expression at least in part through induction of ESR1 and may be useful in treating hypoalphalipoproteinemia.
authors: Division of Endocrinology, Department of Medicine, University of Florida Jacksonville, Jacksonville, FL, USA.
authors: Michael J
authors: MJ
authors: Haas
authors: Biotechnology Laboratory Technology, Florida State College of Jacksonville, Jacksonville, FL, USA.
authors: Luisa M
authors: LM
authors: Onstead-Haas
authors: Division of Endocrinology, Department of Medicine, University of Florida Jacksonville, Jacksonville, FL, USA.
authors: Anna
authors: A
authors: Szafran-Swietlik
authors: Division of Endocrinology, Department of Medicine, University of Florida Jacksonville, Jacksonville, FL, USA.
authors: Hagop
authors: H
authors: Kojanian
authors: Biotechnology Laboratory Technology, Florida State College of Jacksonville, Jacksonville, FL, USA.
authors: Tim
authors: T
authors: Davis
authors: Biotechnology Laboratory Technology, Florida State College of Jacksonville, Jacksonville, FL, USA.
authors: Paul
authors: P
authors: Armstrong
authors: Departments of Medicine and Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada.
authors: Norman C W
authors: NC
authors: Wong
authors: Division of Endocrinology, Department of Medicine, University of Florida Jacksonville, Jacksonville, FL, USA.
authors: Arshag D
authors: AD
authors: Mooradian
mesh_terms: D016632:Apolipoprotein A-I / Q000235:genetics*; D018938:Caco-2 Cells; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology*; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects*; D056945:Hep G2 Cells / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D052456:Hypoalphalipoproteinemias / Q000188:drug therapy; D007529:Isoflavones / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016632:Apolipoprotein A-I; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005419:Flavonoids; D007529:Isoflavones; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; C016527:isoquercitrin; D000077267:Fulvestrant; D004958:Estradiol; C040015:myricetin; D011794:Quercetin
keywords: Coronary artery disease; Estrogen; Hepatocyte; High-density lipoprotein; Phytosterol