What question did this study set out to answer?

To determine whether lipoprotein lipase-enhanced binding of LDL and VLDL to heparan sulfate proteoglycans leads to cellular internalization via the LDL receptor.

May 1, 1993Journal of Biological ChemistryOpen Access

Low density lipoprotein receptor internalizes low density and very low density lipoproteins that are bound to heparan sulfate proteoglycans via lipoprotein lipase

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Population

HepG2 cells and fibroblasts (including LDL receptor-negative fibroblasts)

Comparison

Lipoprotein lipase addition vs Absence of LPL or LDL receptor-negative…

Design

Preclinical

Authors

MMMonique MulderErasmus MC PLPietro LombardiFederico II University Hospital HJHans JansenJikei University School of Medicine

Discussion

Member takes

Implication

LPL may enhance lipoprotein retention on proteoglycans in animal models; leaves open relevance to human atherosclerosis.

Key Points

To determine whether lipoprotein lipase-enhanced binding of LDL and VLDL to heparan sulfate proteoglycans leads to cellular internalization via the LDL receptor.
Measured binding, uptake, and lysosomal degradation of radiolabeled LDL and VLDL in HepG2 cells and fibroblasts treated with 3.4 µg/ml lipoprotein lipase.
Performed Scatchard analyses and monitored internalization kinetics at 4 °C and 37 °C across normal fibroblasts, LDL receptor-negative fibroblasts, and cells with down-regulated LDL receptor activity.
Lipoprotein lipase increased lipoprotein binding sites and affinity 20- to 30-fold and stimulated uptake and lysosomal degradation up to 25-fold after 5 hours at 37 °C.
Enhanced lipoprotein uptake failed to occur in LDL receptor-negative fibroblasts and was proportionally reduced following receptor down-regulation, despite unaltered surface binding.
Initial internalization rate of heparan sulfate proteoglycan-bound LDL was 0.58 ng/min/mg cell protein, demonstrating uptake rates similar to standard LDL receptor-mediated internalization (0.44 ng/min/mg cell protein).

Structured PICO

Population

HepG2 cells and fibroblasts (including LDL receptor-negative fibroblasts)

Intervention

Lipoprotein lipase (LPL) addition (e.g., 3.4 micrograms/ml)

Comparator

Absence of LPL or LDL receptor-negative fibroblasts

Outcome

Binding, uptake, and lysosomal degradation of LDL and VLDLsurrogate

LPL enhances the binding of LDL and VLDL to cell surface proteoglycans, which are subsequently internalized primarily through the LDL receptor pathway.

Cite This Study

Mulder et al. (1993) studied this question.

synapsesocial.com/papers/6a702e4e5d37378ac1dd400b https://doi.org/10.1016/s0021-9258(18)98359-6

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Low density lipoprotein receptor internalizes low density and very low density lipoproteins that are bound to heparan sulfate proteoglycans via lipoprotein lipase

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Low density lipoprotein receptor internalizes low density and very low density lipoproteins that are bound to heparan sulfate proteoglycans via lipoprotein lipase

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider