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High density lipoprotein subpopulations from galactosamine-treated rats and their transformation by lecithin:cholesterol acyltransferase
Journal article   Open access   Peer reviewed

High density lipoprotein subpopulations from galactosamine-treated rats and their transformation by lecithin:cholesterol acyltransferase

J E Matsuura and J B Swaney
Journal of lipid research, v 32(4), pp 581-594
Apr 1991
DOI: https://doi.org/10.1016/S0022-2275(20)42045-0
PMID: 1906919
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/s0022-2275(20)42045-0View
Published, Version of Record (VoR) Open
url
https://doi.org/10.1016/S0022-2275(20)42045-0View
Published, Version of Record (VoR) Open

Abstract

Animals Apolipoprotein A-I Apolipoproteins A - metabolism Apolipoproteins E - blood Chemical Fractionation Cholesterol Esters - metabolism Cross-Linking Reagents Densitometry Galactosamine - pharmacology Humans Lipoproteins, HDL - blood Lipoproteins, HDL - classification Lipoproteins, HDL - isolation & purification Male Molecular Weight Particle Size Phosphatidylcholine-Sterol O-Acyltransferase - blood Phosphatidylcholine-Sterol O-Acyltransferase - physiology Phospholipids - metabolism Rats Rats, Inbred Strains
It is known that an acute hepatotoxicity is produced in rats by intraperitoneal administration of galactosamine; a consequence of this treatment is a marked deficiency of lecithin:cholesterol acyltransferase (LCAT) activity in the plasma compartment. In this study high density lipoprotein (HDL) from galactosamine-treated rats was isolated, resolved into subpopulations, and characterized. In contrast to HDL from control rats, which elutes from gel filtration columns as a single peak and has a diameter of 13.1 nm, HDL from the galactosamine-treated animals was found to elute in five major zones with diameters of 7.8-35 nm. Characterization of these subpopulations has revealed that the larger fractions are enriched in apolipoprotein E, phospholipid, and cholesterol, but contain little cholesteryl ester, while the smallest two fractions contain mainly apolipoprotein A-I, are enriched in phospholipid, and have 50-60% of their cholesterol in the ester form. Incubation of HDL from treated rats with a source of LCAT activity plus low and very low density lipoproteins caused transformation of these subpopulations into a species which, by size and composition, was essentially identical to control rat HDL. In addition, when the subpopulations were individually incubated with purified human lecithin:cholesterol acyltransferase and bovine serum albumin, there was a similar convergence toward a moderate particle size approximating control rat HDL. Cross-linking studies showed that incubation with LCAT activity reduced the heterogeneity of the treated rat HDL. We conclude that the galactosamine treatment induces a complex mixture of HDL that bears strong similarities to the small, apoA-I rich and large, apoE-rich particles seen in LCAT deficiency or secreted by hepatic cells in culture. Furthermore, these species appear to coalesce in the presence of the d greater than 1.21 g/ml fraction of control serum to yield a fairly homogeneous population that resembles control rat HDL in size, composition, and apoprotein content.

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Web of Science research areas
Biochemistry & Molecular Biology
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