title: Dietary flavones counteract phorbol 12-myristate 13-acetate-induced SREBP-2 processing in hepatic cells.
abstract: Consumption of fruits and vegetables is generally regarded as beneficial to plasma lipid profile. The mechanism by which the plant foods induce desirable lipid changes remains unclear. SREBP-2 is crucial in cholesterol metabolism, and it is a major regulator of the cholesterol biosynthesis enzyme HMGCR. Our lab has previously illustrated that apigenin and luteolin could attenuate the nuclear translocation of SREBP-2 through an AMPK-dependent pathway. In the present study, these two flavones were studied for their ability to deter the same in an AMPK-independent signaling route. The processing of SREBP-2 protein was promoted by phorbol 12-myristate 13-acetate (PMA) in the hepatic cells WRL and HepG2, and the increased processing was reversed by apigenin or luteolin co-administration. EMSA results demonstrated that the PMA-induced DNA-binding activity was weakened by the flavones. The increased amount of nuclear SREBP-2 in cells was attenuated by the flavonoid as shown by immunocytochemical imaging. Quantitative reverse transcriptase-polymerase chain reaction assay demonstrated that the transcription of HMGCR under both flavone treatments was reduced. However, apigenin appeared to be stronger than luteolin in restraining PMA-induced HMGCR mRNA expression. Since PMA is a diacylglycerol analog, these findings might have some physiological implications.
authors: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors: Yan Qin
authors: YQ
authors: Tan
authors: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors: Tsz Yan
authors: TY
authors: Wong
authors: Department of Food Science, National Chiayi University, Chiayi City, Taiwan, ROC.
authors: Shu-Mei
authors: SM
authors: Lin
authors: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong. laikleung@cuhk.edu.hk.|Biochemistry Programmes, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong. laikleung@cuhk.edu.hk.|Food and Nutritional Sciences/Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Rm.507C MMW Bldg, Shatin, N.T., Hong Kong. laikleung@cuhk.edu.hk.
authors: Lai K
authors: http://orcid.org/0000-0002-7781-3099
authors: LK
authors: Leung
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D047310:Apigenin / Q000494:pharmacology*; D019587:Dietary Supplements; D056945:Hep G2 Cells; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D047311:Luteolin / Q000494:pharmacology*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
chemical_list: C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; D047310:Apigenin; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases; D055372:AMP-Activated Protein Kinases; D047311:Luteolin; D013755:Tetradecanoylphorbol Acetate
keywords: Apigenin; HMGCR; Luteolin; Nuclear translocation; PKC-dependent pathway; SREBP-2