title: Endocytic pathway and resistance to cholesterol depletion of cholesterol derived cationic lipids for gene delivery.
abstract: Cholesterol-based cationic lipids have been widely used because of biocompatibility and serum resistance. However, the reason for the effectiveness of cholesterol-based cationic lipids remains unclear. We compared the transfection route of CHOL-E, a cholesterol-based cationic lipid having an amine head and an ether linker, with that of DOTAP. The luciferase assay with chemical inhibitors and microscopic observation of pathway markers revealed that clathrin mediated endocytosis is the main pathway for CHOL-E and DOTAP. However, CHOL-E showed resistance to cholesterol depletion by methyl-β-cyclodextrin. Furthermore, CHOL-E recovered the transfection efficiency of DOTAP from cholesterol depletion. These results suggested that superior transfection of CHOL-E might be partly derived from effects on the cell membrane.
authors.affiliation: Department of Physiology and §Department of Internal Medicine College of Medicine, Yeungnam University , Daegu 705-717, Korea.
authors.forename: Yun-Ui
authors.initials: YU
authors.lastname: Bae
authors.forename: Bieong-Kil
authors.initials: BK
authors.lastname: Kim
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Seu
authors.forename: Kyung-Oh
authors.initials: KO
authors.lastname: Doh
mesh_terms: D000818:Animals; D019556:COS Cells; D002412:Cations / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism*; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000502:physiology*; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D008563:Membrane Lipids / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000378:metabolism*; D047392:beta-Cyclodextrins / Q000378:metabolism*
chemical_list: D002412:Cations; D005229:Fatty Acids, Monounsaturated; D008563:Membrane Lipids; D000644:Quaternary Ammonium Compounds; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane