Journal of Lipid Research, Vol 32, 581-594, Copyright © 1991 by Lipid Research, Inc.
High density lipoprotein subpopulations from galactosamine-treated rats and their transformation by lecithin:cholesterol acyltransferase
JE Matsuura and JB Swaney
Department of Biological Chemistry, Hahnemann University, Philadelphia, PA 19102.
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.