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Recognition of solubilized apoproteins from delipidated, oxidized low density lipoprotein (LDL) by the acetyl-LDL receptor

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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Macrophages express a specific receptor that recognizes acetylated low density lipoprotein (LDL) and certain other chemically modified forms of LDL but not native LDL. LDL oxidatively modified either by incubation with endothelial cells in Ham's F-10 medium or by incubation with 5 ..mu..M copper(II) ion in the absence of cells is recognized by this same receptor. This oxidative modification, whether cell-induced or copper-catalyzed, is accompanied by many changes in the physical and chemical properties of LDL, including an increase in density, conversion of phosphatidylcholine to lysophosphatidylcholine, generation of lipid peroxides, and degradation of apolipoprotein B-100. Which changes are essential for eliciting the recognition by the receptor is not known. In the present paper it is shown that fragments of the degraded apolipoprotein from delipidated, oxidized LDL can be almost quantitatively resolubilized using n-octyl ..beta..-D-glucopyranoside. These /sup 125/I-labeled, solubilized apoproteins were degraded rapidly by mouse peritoneal macrophages, and that degradation was competitively inhibited by unlabeled acetyl-LDL and endothelial cell-modified LDL but not by native LDL. These results show that the acetyl-LDL receptor recognizes an epitope on the apoprotein moiety, either newly generated or exposed as a result of oxidative modification, rather than some oxidized lipid moiety. Further, the results suggest that the lipids of oxidatively modified LDL do not play an obligatory role in determining the conformation of that epitope.

Research Organization:
Univ. of California, San Diego, La Jolla
OSTI ID:
6276796
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:2; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETYLATION
ACYLATION
ALKALI METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
APOLIPOPROTEINS
BIODEGRADATION
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
DECOMPOSITION
HALIDES
HALOGEN COMPOUNDS
INORGANIC PHOSPHORS
IODIDES
IODINE COMPOUNDS
LABELLED COMPOUNDS
LIPIDS
LIPOPROTEINS
MACROPHAGES
MAMMALS
MEMBRANE PROTEINS
MICE
ORGANIC COMPOUNDS
OXIDATION
PHAGOCYTES
PHOSPHORS
PROTEINS
RABBITS
RECEPTORS
RODENTS
SODIUM COMPOUNDS
SODIUM IODIDES
SOMATIC CELLS
VERTEBRATES