In vitro activation of the enzymic activity of hepatic lipase by apoA‐II

Jahn, Christine; Osborne, James C.; Schaefer, Ernst J.; Brewer, H. Bryan

doi:10.1016/0014-5793(81)80405-x

Cited by 71 publications

(20 citation statements)

References 23 publications

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“…On the one hand, it has been suggested that apoA-II inhibits (9, 10), while others have found that it enhances, HL-mediated hydrolysis of HDL triacylglycerol (7,8,38,39). Mowri et al (38) reported that hydrolysis of phospholipids and triacylglycerol in HDL is greater in (A-I/A-II)HDL 2 compared with (A-I)HDL 2 .…”

Section: Discussionmentioning

confidence: 99%

“…Unlike lipoprotein lipase (LPL), which requires apolipoprotein C-II (apoC-II) for maximal activity, there is no known protein cofactor for HL. However, there is some conflicting evidence to suggest that the apoA-II in HDL may influence the HL-mediated hydrolysis of triacylglycerol in HDL (7)(8)(9)(10). Some investigators have reported that apoA-II enhances (7,8), while others have concluded that it inhibits, the HL-mediated hydrolysis of triacylglycerol in HDL (9,10).…”

Section: Hepatic Lipase (Hl)mentioning

confidence: 99%

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The Influence of Apolipoproteins on the Hepatic Lipase-mediated Hydrolysis of High Density Lipoprotein Phospholipid and Triacylglycerol

Hime¹,

Barter²,

Rye³

1998

Journal of Biological Chemistry

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This study describes the influence of apolipoproteins on the hepatic lipase (HL)-mediated hydrolysis of phospholipids and triacylglycerol in high density lipoproteins (HDL). HL-mediated hydrolysis was assessed in well characterized, homogeneous preparations of spherical reconstituted high density lipoproteins (rHDL). Hepatic lipase (HL)1 is a 476-amino acid glycoprotein of molecular weight 64,000 -69,000 (1) that is bound to liver sinusoidal endothelial cells (2). HL hydrolyzes acyl ester bonds of triacylglycerol and the sn-1 acyl ester bond of phospholipids. The main plasma substrates for HL are very low density lipoproteins and high density lipoproteins (HDL). The role of HL in HDL metabolism is of considerable importance, as shown by strong negative associations between HL activity and plasma HDL 2 levels (3-5) and the dramatic reduction in the HDL levels of rabbits that have been made transgenic for human HL (6). Unlike lipoprotein lipase (LPL), which requires apolipoprotein C-II (apoC-II) for maximal activity, there is no known protein cofactor for HL. However, there is some conflicting evidence to suggest that the apoA-II in HDL may influence the HL-mediated hydrolysis of triacylglycerol in HDL (7-10). Some investigators have reported that apoA-II enhances (7, 8), while others have concluded that it inhibits, the HL-mediated hydrolysis of triacylglycerol in HDL (9, 10).The present study was carried out in order to determine whether there are significant differences in the HL-mediated hydrolysis of phospholipids and triacylglycerol in HDL that differ in their apolipoprotein composition. This has been achieved by using well defined, homogeneous preparations of spherical reconstituted HDL (rHDL) as substrates for HL. The rHDL were comparable in size and lipid composition and contained either apoA-I or apoA-II as their sole apolipoprotein constituent. The results show that apolipoproteins not only have a major influence on the HL-mediated hydrolysis of the triacylglycerol and phospholipids in rHDL but also regulate the affinity of HL for the rHDL surface. EXPERIMENTAL PROCEDURESPurification of ApoA-I and ApoA-II-ApoA-I and apoA-II were prepared from pooled human plasma donated by the Transfusion Service, Royal Adelaide Hospital. HDL were isolated from the plasma by sequential ultracentrifugation in the 1.07 Ͻ d Ͻ 1.21 g/ml density range (11). The isolated HDL were delipidated (12), and the resulting apoHDL was subjected to anion exchange chromatography on Q Sepharose Fast Flow (Amersham Pharmacia Biotech, Uppsala, Sweden) (13). The purified apoA-I and apoA-II appeared as single bands following electrophoresis on a homogeneous 20% SDS-polyacrylamide PhastGel (Amersham Pharmacia Biotech) and Coomassie staining.

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Section: Discussionmentioning

confidence: 99%

Section: Hepatic Lipase (Hl)mentioning

confidence: 99%

The Influence of Apolipoproteins on the Hepatic Lipase-mediated Hydrolysis of High Density Lipoprotein Phospholipid and Triacylglycerol

Hime¹,

Barter²,

Rye³

1998

Journal of Biological Chemistry

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“…Similarly, apoA-II has been shown to inhibit the lipid transfer activities of cholesteryl ester transfer protein and phospholipid transfer protein (5,18,19), and as such, it is thought to directly affect their ability to control the remodeling and speciation of HDL. The effect of apoA-II on hepatic lipase (HL) is less clear, as there are reports that apoA-II can be both stimulatory (6,20,21) and inhibitory (7) to lipid hydrolysis. Although the studies appear to be in agreement that apoA-II increases the affinity with which HL binds HDL, the effects of apoA-II on overall hydrolytic rates and the rate of free fatty acid release appear to differ.…”

Section: Journal Of Lipid Research Volume 45 2004mentioning

confidence: 99%

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

Boucher

Ramsamy

Braschi

et al. 2004

Journal of Lipid Research

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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.

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“…It has also been reported that LCAT activity is reduced in HDL reconstituted with apoA-II relative to HDL reconstituted with apoA-I (7). Conflicting results have been reported regarding the effect of apoA-II on hepatic lipase, with evidence to support both stimulatory (8) and inhibitory (9,10) effects.…”

mentioning

confidence: 99%

Effects of cholesteryl ester transfer protein inhibition on apolipoprotein A-II-containing HDL subspecies and apolipoprotein A-II metabolism

Brousseau

Millar

Diffenderfer

et al. 2009

Journal of Lipid Research

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This study was designed to establish the mechanism responsible for the increased apolipoprotein (apo) A-II levels caused by the cholesteryl ester transfer protein inhibitor torcetrapib. Nineteen subjects with low HDL cholesterol (,40 mg/dl), nine of whom were also treated with 20 mg of atorvastatin daily, received placebo for 4 weeks, followed by 120 mg of torcetrapib daily for the next 4 weeks. Six subjects in the nonatorvastatin cohort participated in a third phase, in which they received 120 mg of torcetrapib twice daily for 4 weeks. At the end of each phase, subjects underwent a primed-constant infusion of [5,5, H 3 ]L-leucine to determine the kinetics of HDL apoA-II. Relative to placebo, torcetrapib significantly increased apoA-II concentrations by reducing HDL apoA-II catabolism in the atorvastatin (29.4%, P , 0.003) and nonatorvastatin once-(29.9%, P 5 0.02) and twice-(213.2%, P 5 0.02) daily cohorts. Torcetrapib significantly increased the amount of apoA-II in the a-2-migrating subpopulation of HDL when given as monotherapy (27%, P , 0.02; 57%, P , 0.003) or on a background of atorvastatin (28%, P , 0.01). In contrast, torcetrapib reduced concentrations of apoA-II in a-3-migrating HDL, with mean reductions of 214% (P 5 0.23), 218% (P , 0.02), and 218% (P , 0.01) noted during the atorvastatin and nonatorvastatin 120 mg onceand twice-daily phases, respectively. Our findings indicate that CETP inhibition increases plasma concentrations of apoA-II by delaying HDL apoA-II catabolism and significantly alters the remodeling of apoA-II-containing HDL subpopulations.-Brousseau, M. E., J. S. Millar, M. R. Diffenderfer, C. Nartsupha, B. F. Asztalos, M. L. Wolfe, J. P. Mancuso, A. G. Digenio, D. J. Rader, and E. J. Schaefer. Effects of cholesteryl ester transfer protein inhibition on apolipoprotein A-II-containing HDL subspecies and apolipoprotein A-II metabolism.

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In vitro activation of the enzymic activity of hepatic lipase by apoA‐II

Cited by 71 publications

References 23 publications

The Influence of Apolipoproteins on the Hepatic Lipase-mediated Hydrolysis of High Density Lipoprotein Phospholipid and Triacylglycerol

The Influence of Apolipoproteins on the Hepatic Lipase-mediated Hydrolysis of High Density Lipoprotein Phospholipid and Triacylglycerol

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

Effects of cholesteryl ester transfer protein inhibition on apolipoprotein A-II-containing HDL subspecies and apolipoprotein A-II metabolism

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