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PMID:15878877

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Citation

Lookene, A, Beckstead, JA, Nilsson, S, Olivecrona, G and Ryan, RO (2005) Apolipoprotein A-V-heparin interactions: implications for plasma lipoprotein metabolism. J. Biol. Chem. 280:25383-7

Abstract

Transgenic and gene disruption experiments in mice have revealed that apolipoprotein (apo) A-V is a potent regulator of plasma triglyceride (TG) levels. To investigate the molecular basis of apoA-V function, the ability of isolated recombinant apoA-V to modulate lipoprotein lipase (LPL) activity was examined in vitro. With three distinct lipid substrate particles, including very low-density lipoprotein (VLDL), a TG/phospholipid emulsion, or dimyristoylphosphatidylcholine liposomes, apoA-V had little effect on LPL activity. In the absence or presence apolipoprotein C-II, apoA-V marginally inhibited LPL activity. On the other hand, apoA-V-dimyristoylphosphatidylcholine disc particles bound to heparin-Sepharose and were specifically eluted upon application of a linear gradient of NaCl. The interaction of apoA-V with sulfated glycosaminoglycans was further studied by surface plasmon resonance spectroscopy. ApoA-V showed strong binding to heparin-coated chips, and binding was competed by free heparin. ApoA-V enrichment enhanced binding of apoC-II-deficient chylomicrons and VLDL to heparin-coated chips. When LPL was first bound to the heparin-coated chip, apoA-V-enriched chylomicrons showed binding. Finally, human pre- and post-heparin plasma samples were subjected to immunoblot analysis with anti-apoA-V IgG. No differences in the amount of apoA-V present were detected. Taken together, the results show that apoA-V lipid complexes bind heparin and, when present on TG-rich lipoprotein particles, may promote their association with cell surface heparan sulfate proteoglycans. Through such interactions, apoA-V may indirectly affect LPL activity, possibly explaining its inverse correlation with plasma TG levels.

Links

PubMed Online version:10.1074/jbc.M501589200

Keywords

Animals; Apolipoprotein C-III; Apolipoproteins/metabolism; Apolipoproteins A; Apolipoproteins C/metabolism; Blood Proteins/metabolism; Cattle; Cholesterol, VLDL/metabolism; Chromatography, Affinity; Dimyristoylphosphatidylcholine/metabolism; Enzyme Activation; Heparin/metabolism; Humans; Lipoprotein Lipase/metabolism; Liposomes/metabolism; Sepharose; Surface Plasmon Resonance; Triglycerides/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:APOC2

involved_in

GO:0051006: positive regulation of lipoprotein lipase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:APOA5

enables

GO:0008201: heparin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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