Faculty Collaboration Database

Apolipoprotein A-II regulates HDL stability and affects hepatic lipase association and activity. J Lipid Res 2004 May;45(5):849-58

Date

02/18/2004

Pubmed ID

14967812

DOI

10.1194/jlr.M300431-JLR200

Scopus ID

2-s2.0-2142718234 (requires institutional sign-in at Scopus site)   50 Citations

Abstract

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 alpha-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 alpha-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.

Author List

Boucher J, Ramsamy TA, Braschi S, Sahoo D, Neville TA, Sparks DL

Author

Daisy Sahoo PhD Dean, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Apolipoprotein A-II
Electrophoresis, Agar Gel
Esterification
Humans
Lipase
Lipoproteins, HDL
Liver
Molecular Conformation
Particle Size
Phosphatidylcholine-Sterol O-Acyltransferase
Static Electricity