TAILIEUCHUNG - Báo cáo khoa học: Hexadecylphosphocholine interferes with the intracellular transport of cholesterol in HepG2 cells

We have shown, in a previous publication, that nontoxic concentrations of hexadecylphosphocholine exert an antiproliferative effect on HepG2 cells. Hexadecylphosphocholine also interferes with the biosynthesis of choles-terol and phosphatidylcholine. | ỊFEBS Journal Hexadecylphosphocholine interferes with the intracellular transport of cholesterol in HepG2 cells Maria P. Carrasco Jose M. Jimenez-Lopez Josefa L. Segovia and Carmen Marco Department of Biochemistry and Molecular Biology I Faculty of Sciences University of Granada Spain Keywords cholesterolhomeostasis HepG2 cells hexadecylphosphocholine HMG-CoA reductase LDLr Correspondence C. Marco or M. P. Carrasco Department of Biochemistry and Molecular Biology I Faculty of Sciences University of Granada Av. Fuentenueva s n Granada 18001 Spain Fax 34 958 249945 Tel 34 958 243087 E-mail cmarco@ or mpazcj@ Website http bbm1 Received 23 November 2007 revised 31 January 2008 accepted 5 February 2008 doi We have shown in a previous publication that nontoxic concentrations of hexadecylphosphocholine exert an antiproliferative effect on HepG2 cells. Hexadecylphosphocholine also interferes with the biosynthesis of cholesterol and phosphatidylcholine. We have now extended our studies to try to establish the molecular mechanism by which hexadecylphosphocholine disrupts cholesterol homeostasis. Using radiolabelled substrates we determined the effect of hexadecylphosphocholine on cholesterol synthesis the destiny of cholesterol from low-density lipoprotein and the transport of cholesterol between the plasma membrane and the endoplasmic reticulum. Protein levels and gene expression of the main proteins involved in cholesterol homeostasis were analysed by western blotting and RT-PCR respectively. HepG2 cells exposed to hexadecylphosphocholine showed an increase in cholesterol biosynthesis when acetate but not mevalonate was used as a substrate. The activity of 3-hydroxy-3-methylglutaryl-CoA reductase EC and low-density lipoprotein receptor as well as the corresponding mRNA expression increased after 24 h of treatment with hexadecylphosphocholine. Cholesteryl linoleate in low-density lipoprotein uptake and further

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