Enzymatically induced alterations in the structure of rat serum lipoproteins.
Incubation of freshly isolated rat serum induces a large number of changes in the properties of the serum lipoproteins, especially the high density lipoproteins (HDL). The particle diameter of the HDL increases from about 10.4 nm to 12.3 nm and the protein content appears to increase by about 60,000 Daltons. Reactions catalyzed by lecithin:cholesterol acyltransferase (LCAT) lead to a marked decrease in cholesterol and phospholipid content, and an even greater increase in cholesteryl ester content. Especially noteworthy are the marked increases in apoE and apoA-IV which are found associated with HDL as a result of this process. Data indicate that the affinity of apoE and apoA-IV for the HDL particles may be influenced by the proportion of surface to core lipid and by the presence of products of the LCAT reaction. Changes in the apoprotein content of very low density lipoproteins are also observed, with A-I and A-IV appearing in this density interval. All of the above changes can be prevented by the inclusion of 5,5'dithiobis(2-nitrobenzoate) or p-chloromercuriphenylsulfonate during the incubation, or by heat treatment of serum at 56 degrees C for 30 min; these treatments are known to inhibit LCAT activity. It is concluded that LCAT action is the major cause of the various changes in HDL structure that are observed and that alterations in apoprotein content occur to correct the resultant imbalance between core lipid and coverage of this core by amphiphilic components. Increased apoE association with cholesteryl ester-rich HDL may provide an efficient means for receptor-mediated removal of cholesterol from the circulation.
Swaney
J B
JB
Department of Biological Chemistry, Hahnemann University, Philadelphia, PA 19102.
Orishimo
M W
MW
Girard
A
A
D000818:Animals; D002499:Centrifugation, Density Gradient; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D010741:Phospholipases A / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D002785:Sterol O-Acyltransferase / Q000494:pharmacology*
D008075:Lipoproteins, HDL; D002785:Sterol O-Acyltransferase; D010741:Phospholipases A