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Policosanol fails to lower HMG‐CoA reductase activity in HepG2 cells
Author(s) -
Guderian David M.,
Lee JiYoung,
Carr Timothy P.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.700.36
Subject(s) - reductase , hmg coa reductase , gene expression , cholesterol , incubation , chemistry , enzyme , micelle , gene , hydroxymethylglutaryl coa reductase , pharmacology , biology , biochemistry , aqueous solution
The cholesterol‐lowering properties of policosanol are controversial. One research group in Cuba have reported that policosanol intake of 5–10 mg/day in humans can lower plasma LDL cholesterol up to 25%, although other laboratories have failed to repeat these findings. Moreover, the cellular/molecular effects of policosanol are uncertain. Using HepG2 cells, we assessed the regulation of HMG‐CoA reductase (HMGR) activity and gene expression by incubating cells for 1.5, 3.0 or 4.5 hrs with bile salt micelles (taurocholate, lecithin) with and without policosanol. Policosanol uptake into HepG2 cells was confirmed by gas chromatography, demonstrating the efficacy of our micelle delivery system. Our results indicated no significant differences at any time point between control and policosanol treated cells; however, after 4.5 hrs of incubation, HMGR activity was significantly increased in both control and policosanol treated cells, suggesting that prolonged exposure to micelles may promote cholesterol depletion in HepG2 cells. We also quantified mRNA gene expression of HMGR and its transcription factor SREBP2. HMGR mRNA abundance was determined by real‐time PCR and indicated no difference in gene expression after 3 hrs. We conclude that policosanol has little or no effect on HMGR activity or gene expression in HepG2 cells. [Supported by USDA‐NRI Competitive Grant No. 2004‐35503‐14824]