scholarly journals Lupin Peptides Modulate the Protein-Protein Interaction of PCSK9 with the Low Density Lipoprotein Receptor in HepG2 Cells

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Carmen Lammi ◽  
Chiara Zanoni ◽  
Gilda Aiello ◽  
Anna Arnoldi ◽  
Giovanni Grazioso
Keyword(s):  
Protein Interaction ◽  
Hepg2 Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Protein Protein Interaction ◽  
Density Lipoprotein Receptor

scholarly journals Antagonism of Secreted PCSK9 Increases Low Density Lipoprotein Receptor Expression in HepG2 Cells

2009 ◽  
Vol 284 (16) ◽  
pp. 10561-10570 ◽  
Author(s):  
Markey C. McNutt ◽  
Hyock Joo Kwon ◽  
Chiyuan Chen ◽  
Justin R. Chen ◽  
Jay D. Horton ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Receptor Expression ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

scholarly journals Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor

2009 ◽  
Vol 419 (3) ◽  
pp. 577-584 ◽  
Author(s):  
Christopher J. Duff ◽  
Martin J. Scott ◽  
Ian T. Kirby ◽  
Sue E. Hutchinson ◽  
Steve L. Martin ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Catalytic Domain ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Peptide Epitopes ◽  
Density Lipoprotein Receptor ◽  
Ldl Uptake

PCSK9 (proprotein convertase subtilisin/kexin type 9) promotes degradation of the LDLR [LDL (low-density lipoprotein) receptor] through an as-yet-undefined mechanism, leading to a reduction in cellular LDLc (LDL-cholesterol) and a concomitant increase in serum LDLc. Central to the function of PCSK9 is a direct protein–protein interaction formed with the LDLR. In the present study, we investigated a strategy to modulate LDL uptake by blocking this interaction using specific antibodies directed against PCSK9. Studies using surface plasmon resonance demonstrated that direct binding of PCSK9 to the LDLR could be abolished with three different anti-PCSK9 antibodies. Two of these antibodies were raised against peptide epitopes in a region of the catalytic domain of PCSK9 that is involved in the interaction with the LDLR. Such antibodies restored LDL uptake in HepG2 cells treated with exogenous PCSK9 and in HepG2 cells engineered to overexpress recombinant PCSK9. This latter observation indicates that antibodies blocking the PCSK9–LDLR interaction can inhibit the action of PCSK9 produced endogenously in a cell-based system. These antibodies also disrupted the higher-affinity interaction between the natural gain-of-function mutant of PCSK9, D374Y, and the LDLR in both the cell-free and cell-based assays. These data indicate that antibodies targeting PCSK9 can reverse the PCSK9-mediated modulation of cell-surface LDLRs.

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