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Journal of Lipid Research, Vol. 45, 849-858, May 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Apolipoprotein A-II regulates HDL stability and affects hepatic lipase association and activity

Jonathan Boucher^*, Tanya A. Ramsamy^*, Sylvie Braschi^*,, Daisy Sahoo, Tracey A-M. Neville^* and Daniel L. Sparks^1,*

^* Lipoproteins and Atherosclerosis Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada K1Y 4W7
Division of Endocrinology and Metabolism, Ottawa Hospital, and University of Ottawa, Civic Campus, Ottawa, Ontario, Canada K1Y 4E9
Department of Pharmacology, State University of New York at Stony Brook, Stony Brook, NY 11794

¹ To whom correspondence should be addressed. e-mail: dsparks{at}ottawaheart.ca

The effect of apolipoprotein A-II (apoA-II) on the structure and stability of HDL has been investigated in reconstituted HDL particles. Purified human apoA-II was incorporated into sonicated, spherical LpA-I particles containing apoA-I, phospholipids, and various amounts of triacylglycerol (TG), diacylglycerol (DG), and/or free cholesterol. Although the addition of PC to apoA-I reduces the thermodynamic stability (free energy of denaturation) of its -helices, PC has the opposite effect on apoA-II and significantly increases its helical stability. Similarly, substitution of apoA-I with various amounts of apoA-II significantly increases the thermodynamic stability of the particle -helical structure. ApoA-II also increases the size and net negative charge of the lipoprotein particles. ApoA-II directly affects apoA-I conformation and increases the immunoreactivity of epitopes in the N and C termini of apoA-I but decreases the exposure of central domains in the molecule (residues 98–186). ApoA-II appears to increase HL association with HDL and inhibits lipid hydrolysis. ApoA-II mildly inhibits PC hydrolysis in TG-enriched particles but significantly inhibits DG hydrolysis in DG-rich LpA-I. In addition, apoA-II enhances the ability of reconstituted LpA-I particles to inhibit VLDL-TG hydrolysis by HL.

Therefore, apoA-II affects both the structure and the dynamic behavior of HDL particles and selectively modifies lipid metabolism.

Abbreviations: apoA-I, apolipoprotein A-I; CE, cholesteryl ester; D_1/2, midpoint of the guanidine hydrochloride denaturation curve; DG, diacylglycerol; G_D^o, free energy of denaturation; ED₅₀, concentration required to inhibit 50% of the maximal binding of the antibodies to the apoHDL-coated plate; FC, free cholesterol; GdnHCl, guanidine hydrochloride; HL, hepatic lipase; LpA-I, reconstituted HDL complexes containing apoA-I; LpA-I/A-II, reconstituted HDL complexes containing apoA-I and apoA-II; LpA-II, reconstituted HDL complexes containing apoA-II; mAb, monoclonal antibody; POPC, 1-palmitoyl-2-oleoyl phosphatidylcholine; TG, triacylglycerol

Supplementary key words lecithin:cholesterol acyltransferase • very low density lipoprotein • high density lipoprotein • thermodynamic stability • free energy of denaturation • apolipoprotein A-I • denaturation • lipolysis

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