title: Lipid efflux mediated by alkylphospholipids in HepG2 cells.
abstract: Antitumoural alkylphospholipid (APL) analogues alter cholesterol homoeostasis in HepG2 cells by interfering with cholesterol transport from the plasma membrane to the endoplasmic reticulum (ER) and at the same time stimulating the release of considerable quantities of membrane cholesterol. The capacity of APLs to stimulate cholesterol efflux is suppressed when cells are incubated simultaneously with APLs and serum whilst the inhibition of cholesterol transport to the ER (measured in terms of the synthesis of esterified cholesterol) persists, indicating that both effects are independent of each other. Interestingly, our results suggest that both raft and non-raft membrane domains contribute to the cholesterol released to APLs. In addition, a marked efflux of choline-bearing phospholipids (phosphatidylcholine (PC) and sphingomyelins (SM)) was found to be related to this release of cholesterol. Finally, we observed that APL micelles composed of cholesterol might act as donor/acceptor cholesterol systems. Thus, the findings of this study clearly demonstrate that antitumoural APLs act as extracellular acceptors, stimulating cholesterol and phospholipid efflux, although they may also play a role as cholesterol donors.
authors: Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Granada, Spain.
authors: Pablo
authors: P
authors: Ríos-Marco
authors: Josefa L
authors: JL
authors: Segovia
authors: José M
authors: JM
authors: Jiménez-López
authors: Carmen
authors: C
authors: Marco
authors: María P
authors: MP
authors: Carrasco
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007700:Kinetics; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010743:Phospholipids; D010767:Phosphorylcholine; C039128:miltefosine; D002784:Cholesterol; D013108:Sphingomyelin Phosphodiesterase