Remnant high density lipoprotein2 particles produced by hepatic lipase display high-affinity binding and increased endocytosis into a human hepatoma cell line (HEPG2).
We had previously shown that hepatic lipase plays a prominent role in promoting the generation of pre-beta HDL particles from triglyceride rich HDL2, leaving an alpha-HDL particle of decreased size that was named "remnant HDL2" [Barrans, A., et al. (1994) J. Biol. Chem. 269, 11572-11577]. Interestingly, this remnant HDL2 was rapidly cleared by the liver, suggesting a particularly high affinity of those remnant HDL2 for liver cells. In the present study, we attempted to characterize the interaction of remnant HDL2 with HepG2 cells, as compared to those of native triglyceride rich HDL2. Two main observations were made. First, while triglyceride rich HDL2 particles were able to bind only the low-affinity binding sites, the remaining particle generated after hepatic lipase lipolysis the remnant HDL2 was further able to bind to the high-affinity binding sites. Competition experiments indicate that these two remnant HDL2 binding sites were the same as the two HDL3 binding sites previously described [Barbaras, R., et al. (1994) Biochemistry 33, 2335-2340]. This is the first observation on the remodeling dependence of HDL binding onto hepatocytes. Second, following binding on those two binding sites, the remnant HDL2 were faster internalized and in higher amounts than the native triglyceride rich HDL2. All together, these observations suggest that the continuous remodeling of HDL induces different binding and internalization characteristics of the HDL particles and that the high-affinity HDL binding sites might trigger the internalization of apo HDL through the low-affinity binding sites.
Institut National de la santé et de la Recherche Médicale (INSERM) - Unité 326, Hopital Purpan, Toulouse, France.
K
K
Guendouzi
X
X
Collet
B
B
Perret
H
H
Chap
R
R
Barbaras
D001667:Binding, Competitive; D004705:Endocytosis; D018197:Hepatoblastoma / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008049:Lipase / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D053439:Lipoproteins, HDL2; D008099:Liver / Q000201:enzymology*; D011485:Protein Binding; D014280:Triglycerides / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008075:Lipoproteins, HDL; D053439:Lipoproteins, HDL2; D014280:Triglycerides; D008049:Lipase