title: The flavone apigenin blocks nuclear translocation of sterol regulatory element-binding protein-2 in the hepatic cells WRL-68.
abstract: Sterol regulatory element-binding protein-2 (SREBP-2) is a pivotal transcriptional factor in cholesterol metabolism. Factors interfering with the proper functioning of SREBP-2 potentially alter plasma lipid concentrations. Consuming fruits and vegetables is associated with beneficial plasma lipid profile. The mechanism by which plant foods induce desirable lipid changes remains unclear. Apigenin, a common plant food flavonoid, was shown to modulate the nuclear translocation of SREBP-2 in the hepatic cells WRL-68 in the present study. The processing of SREBP-2 protein occurred after translation, and apigenin blocked this activation route. Further examination indicated that AMP-activated protein kinase (AMPK) was activated by the flavone, and co-administrating the AMPK-specific inhibitor compound C could release the blockage. Reporter gene assay revealed that the transactivation of sterol responsive element (SRE)-containing 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) promoter was suppressed by the flavone. Similarly, electromobility shift assay result also demonstrated a reduced DNA-binding activity on the SRE domain under the same treatment. The reduced transactivity and DNA-binding activity could be attributed to a decreased amount of SREBP-2 translocating from cytosol to nucleus as depicted by confocal microscopy. Quantitative RT-PCR assay demonstrated that the transcription of HMGCR followed the same pattern of SREBP-2 translocation. In summary, the present study showed that apigenin prevented SREBP-2 translocation and reduced the downstream gene HMGCR transcription. The minimum effective dosage should be achievable in the form of functional food consumption or dietary supplementation.
authors.affiliation: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong,Room 507C, MMW Building,Shatin,NT,Hong Kong.
authors.forename: Tsz Yan
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Department of Food Science,National Chiayi University,Chiayi City,Taiwan,ROC.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Lin
authors.affiliation: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong,Room 507C, MMW Building,Shatin,NT,Hong Kong.
authors.forename: Lai K
authors.initials: LK
authors.lastname: Leung
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D047310:Apigenin / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects*; D003600:Cytosol / Q000737:chemistry; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000235:genetics; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D050603:Squalene Monooxygenase / Q000235:genetics; D051782:Sterol Regulatory Element Binding Protein 2 / Q000032:analysis / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D051782:Sterol Regulatory Element Binding Protein 2; D047310:Apigenin; D006903:Hydroxymethylglutaryl CoA Reductases; D008156:Luciferases; D050603:Squalene Monooxygenase; D006904:Hydroxymethylglutaryl-CoA Synthase; D011494:Protein Kinases; D055372:AMP-Activated Protein Kinases
keywords: 3-Hydroxy-3-methylglutaryl-CoA reductase; Apigenin; Nuclear translocation; Sterol regulatory element-binding protein-2