Lactoferrin binding to heparan sulfate proteoglycans and the LDL receptor-related protein. Further evidence supporting the importance of direct binding of remnant lipoproteins to HSPG.
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Discussion
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Implication
In vitro study reveals dual binding of lactoferrin to HSPG and LRP in cultured mammalian cells, indicating direct proteoglycan involvement in remnant lipoprotein clearance.
Key Points
- To determine whether lactoferrin inhibits the clearance of remnant lipoproteins by directly interacting with cell-surface heparan sulfate proteoglycans and the LDL receptor-related protein.
- Measured binding and degradation of radiolabeled 125I-lactoferrin and 125I-39-kd protein in cultured HepG2 hepatocytes, wild-type Chinese hamster ovary (CHO) cells, and HSPG-deficient mutant CHO cells (pgsD-677).
- Treated cells with heparinase to enzymatically cleave cell-surface HSPG and used the 39-kd receptor-associated protein to competitively block LRP ligand interactions.
- Heparinase treatment inhibited 125I-lactoferrin binding by 45% to 60% in HepG2 and wild-type CHO cells, and mutant CHO cells lacking HSPG demonstrated approximately 50% of wild-type binding levels.
- The 39-kd protein inhibited 125I-lactoferrin degradation by 60% to 65% in wild-type CHO cells, and combining 39-kd protein with heparinase reduced total binding by 85% to 90%.
- Heparinase digestion decreased 125I-39-kd protein binding by approximately 40% in wild-type cells, and HSPG-lacking mutant cells bound 50% less 39-kd protein than wild-type cells.
Cite This Study
Ji et al. (1994) studied this question.