Endocytosis of Hepatic Lipase and Lipoprotein Lipase into Rat Liver Hepatocytes in Vivo Is Mediated by the Low Density Lipoprotein Receptor-related Protein

Marcel Vergés, Andre Bensadoun, Joachim Herz, John D Belcher, Richard J. Havel

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18 Citations (Scopus)

Abstract

In isolated cell studies, the internalization and degradation of hepatic lipase (HL) has been linked to its binding to the low density lipoprotein receptor-related protein (LRP). We have utilized the receptor-associated protein (RAP), a universal inhibitor of high affinity ligand binding to LRP, to evaluate the participation of LRP in the endocytosis of HL and lipoprotein lipase (LPL). We isolated a total endosome fraction from rat livers after a 30-min infusion of recombinant RAP, administered as a glutathione S-transferase conjugate (GST-RAP). GST-RAP infusion had no effect on the concentration of HL in liver homogenates, but its concentration in blood plasma increased progressively by 20%, and enrichment over homogenate of HL in endosomes was reduced by 50% as compared with infusion of GST alone. The concentrations of LPL in liver and plasma were 1.4 and 0.5%, respectively, those of HL, but endosomal enrichment of the two enzymes was similar (∼10-fold). GST-RAP infusion had no effect on the concentration of LPL in liver but increased its concentration in blood plasma by 250% and reduced its endosomal enrichment by 95% or greater. GST-RAP infusion also reduced endosomal enrichment of LRP by 40%, but enrichment of several other endocytic receptors was unaffected. Endosomal enrichment of several membrane trafficking proteins associated with the endocytic pathway in hepatocytes was unaffected by GST-RAP with the exception of early endosome endosome antigen 1, which was reduced by 85% We conclude that HL is partially and LPL almost exclusively taken up into rat hepatocytes after binding to the endocytic receptor LRP.

Original languageEnglish (US)
Pages (from-to)9030-9036
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number10
DOIs
StatePublished - Mar 5 2004

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LDL-Receptor Related Proteins
Lipoprotein Lipase
LDL Receptors
Lipases
Endocytosis
Lipase
Liver
Rats
Hepatocytes
Lipoprotein Receptors
Endosomes
Proteins
Plasmas
Blood
Glutathione Transferase
Membrane Proteins

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Endocytosis of Hepatic Lipase and Lipoprotein Lipase into Rat Liver Hepatocytes in Vivo Is Mediated by the Low Density Lipoprotein Receptor-related Protein. / Vergés, Marcel; Bensadoun, Andre; Herz, Joachim; Belcher, John D; Havel, Richard J.

In: Journal of Biological Chemistry, Vol. 279, No. 10, 05.03.2004, p. 9030-9036.

Research output: Contribution to journalArticle

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abstract = "In isolated cell studies, the internalization and degradation of hepatic lipase (HL) has been linked to its binding to the low density lipoprotein receptor-related protein (LRP). We have utilized the receptor-associated protein (RAP), a universal inhibitor of high affinity ligand binding to LRP, to evaluate the participation of LRP in the endocytosis of HL and lipoprotein lipase (LPL). We isolated a total endosome fraction from rat livers after a 30-min infusion of recombinant RAP, administered as a glutathione S-transferase conjugate (GST-RAP). GST-RAP infusion had no effect on the concentration of HL in liver homogenates, but its concentration in blood plasma increased progressively by 20{\%}, and enrichment over homogenate of HL in endosomes was reduced by 50{\%} as compared with infusion of GST alone. The concentrations of LPL in liver and plasma were 1.4 and 0.5{\%}, respectively, those of HL, but endosomal enrichment of the two enzymes was similar (∼10-fold). GST-RAP infusion had no effect on the concentration of LPL in liver but increased its concentration in blood plasma by 250{\%} and reduced its endosomal enrichment by 95{\%} or greater. GST-RAP infusion also reduced endosomal enrichment of LRP by 40{\%}, but enrichment of several other endocytic receptors was unaffected. Endosomal enrichment of several membrane trafficking proteins associated with the endocytic pathway in hepatocytes was unaffected by GST-RAP with the exception of early endosome endosome antigen 1, which was reduced by 85{\%} We conclude that HL is partially and LPL almost exclusively taken up into rat hepatocytes after binding to the endocytic receptor LRP.",
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