α-Tocopherol (αTocH) is transported in association with lipoproteins in the aqueous milieu of the plasma. Although up to 50% of circulating αTocH is transported by high-density lipoproteins (HDLs), little is known about the mechanisms of uptake of HDL-associated αTocH. During the current study, human apolipoprotein (apo)E-free HDL subclass 3 (HDL3) labelled with [14C]αTocH was used to investigate uptake mechanisms of HDL3-associated αTocH by a permanent hepatoblastoma cell line (HepG2). HDL3-associated αTocH was taken up independently of HDL3 holoparticles in excess of apoA-I comparable with the non-endocytotic delivery of cholesteryl esters to cells termed the ‘selective ’ cholesteryl ester uptake pathway. Experiments with unlabelled HDL3 demonstrated net mass transfer of αTocH to HepG2 cells. Time-dependent studies with [14C]αTocH-labelled HDL3 revealed tracer uptake in 80-fold excess of apoA-I and in 4-fold excess of cholesteryl linoleate. In addition to HLDs, low-density lipoprotein (LDL)-associated αTocH was also taken up in excess of holoparticles, although to a lesser extent. These findings were confirmed with unlabelled lipoprotein preparations, in which HDL3 displayed a 2- to 3-fold higher αTocH donor efficiency than LDLs (lipoproteins adjusted for equal amounts of αTocH). An important factor affecting particle-independent uptake of αTocH was the cellular cholesterol content (a 2-fold increase in cellular cholesterol levels resulted in a 2.3-fold decrease in uptake). Pulse–chase studies demonstrated that some of the HDL3-associated αTocH taken up independently of holoparticle uptake was resecreted along with a newly synthesized apoB-containing lipoprotein fraction.
High-density lipoprotein (HDL3)-associated α-tocopherol is taken up by HepG2 cells via the selective uptake pathway and resecreted with endogenously synthesized apo-lipoprotein B-rich lipoprotein particles
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Daniel GOTI, Helga REICHER, Ernst MALLE, Gerhard M. KOSTNER, Ute PANZENBOECK, Wolfgang SATTLER; High-density lipoprotein (HDL3)-associated α-tocopherol is taken up by HepG2 cells via the selective uptake pathway and resecreted with endogenously synthesized apo-lipoprotein B-rich lipoprotein particles. Biochem J 15 May 1998; 332 (1): 57–65. doi: https://doi.org/10.1042/bj3320057
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