title: The Flavone Luteolin Suppresses SREBP-2 Expression and Post-Translational Activation in Hepatic Cells.
abstract: High blood cholesterol has been associated with cardiovascular diseases. The enzyme HMG CoA reductase (HMGCR) is responsible for cholesterol synthesis, and inhibitors of this enzyme (statins) have been used clinically to control blood cholesterol. Sterol regulatory element binding protein (SREBP) -2 is a key transcription factor in cholesterol metabolism, and HMGCR is a target gene of SREBP-2. Attenuating SREBP-2 activity could potentially minimize the expression of HMGCR. Luteolin is a flavone that is commonly detected in plant foods. In the present study, Luteolin suppressed the expression of SREBP-2 at concentrations as low as 1 μM in the hepatic cell lines WRL and HepG2. This flavone also prevented the nuclear translocation of SREBP-2. Post-translational processing of SREBP-2 protein was required for nuclear translocation. Luteolin partially blocked this activation route through increased AMP kinase (AMPK) activation. At the transcriptional level, the mRNA and protein expression of SREBP-2 were reduced through luteolin. A reporter gene assay also verified that the transcription of SREBF2 was weakened in response to this flavone. The reduced expression and protein processing of SREBP-2 resulted in decreased nuclear translocation. Thus, the transcription of HMGCR was also decreased after luteolin treatment. In summary, the results of the present study showed that luteolin modulates HMGCR transcription by decreasing the expression and nuclear translocation of SREBP-2.
authors: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., People's Republic of China.
authors: Tsz Yan
authors: TY
authors: Wong
authors: Dept. of Food Science, National Chiayi University, Chiayi City, Taiwan, (R.O.C.).
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 S.A.R., People's Republic of China; Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., People's Republic of China.
authors: Lai K
authors: LK
authors: Leung
mesh_terms: D000263:Adenylate Kinase / Q000235:genetics; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis* / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects; D047311:Luteolin / Q000008:administration & dosage*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051782:Sterol Regulatory Element Binding Protein 2 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; D006903:Hydroxymethylglutaryl CoA Reductases; D000263:Adenylate Kinase; D047311:Luteolin