scholarly journals Effects of charged lipids on the interaction of cholesteryl ester transfer protein with lipid microemulsions

1997 ◽  
Vol 322 (1) ◽  
pp. 159-165 ◽  
Author(s):  
Otthakal V. RAJARAM ◽  
William H. SAWYER
Keyword(s):  
Cholesteryl Ester ◽  
Surface Charge ◽  
Rate Constant ◽  
Cholesteryl Ester Transfer Protein ◽  
Egg Yolk ◽  
Order Rate Constant ◽  
Cholesteryl Oleate ◽  
Dissociation Rate ◽  
Excimer Fluorescence ◽  
Transfer Protein

This study reports the effects of charged lipids on the transfer of cholesteryl-1-pyrene decanoate (Py-CE) between apolipoprotein-free microemulsion particles mediated by cholesteryl ester transfer protein (CETP). The surface charge characteristics of microemulsion particles composed of cholesteryl oleate and egg yolk phosphatidylcholine were altered by incorporating phosphatidylserine, oleate or stearylamine into the phosphatidylcholine that forms the surface monolayer of the particle. The transfer of Py-CE was measured continuously by following the decrease in excimer fluorescence that accompanies the transfer of the probe from donor to acceptor particles [Rajaram, Chan and Sawyer (1994) Biochem. J. 304, 423Ő430]. The inclusion of 20 mol% phosphatidylserine relative to the phospholipid in the surface monolayer of the emulsion caused a 64% decrease in the first-order rate constant describing the transfer. An increase in ionic strength caused a partial reversal of this effect, indicating that electrostatic factors are only partially responsible for the interaction with lipid. Complete inhibition of transfer was observed when 10 mol% sodium oleate was incorporated into the surface monolayer. The incorporation of stearylamine into the emulsion caused a 32% increase in the transfer rate. The binding of CETP to the different emulsion surfaces was also examined using a surface plasmon resonance biosensor. The presence of negatively charged lipid (phosphatidylserine or oleic acid) decreased the rate of association of CETP with the emulsion without a significant change in the dissociation rate constant. The presence of the positively charged lipid stearylamine increased the rate of association of CETP with the lipid surface. It is concluded that a negative surface charge on the monolayer decreases the rate of transfer by decreasing the affinity of CETP for these particles.

Cholesteryl ester transfer protein (CETP) increases postprandial triglyceridaemia and delays triacylglycerol plasma clearance in transgenic mice

2009 ◽  
Vol 419 (3) ◽  
pp. 629-634 ◽  
Author(s):  
Alessandro G. Salerno ◽  
Patrícia R. Patrício ◽  
Jairo A. Berti ◽  
Helena C. F. Oliveira
Keyword(s):  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Plasma Clearance ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Kinetic Studies ◽  
Cholesteryl Oleate ◽  
Liver Uptake ◽  
Transfer Protein

The CETP (cholesteryl ester transfer protein) is a plasma protein synthesized in several tissues, mainly in the liver; CETP reduces plasma HDL (high-density lipoprotein) cholesterol and increases the risk of atherosclerosis. The effect of CETP levels on postprandial intravascular metabolism of TAGs (triacylglycerols) is an often-overlooked aspect of the relationship between CETP and lipoprotein metabolism. Here, we tested the hypothesis that CETP delays the plasma clearance of TAG-rich lipoprotein by comparing human CETP expressing Tg (transgenic) and non-Tg mice. After an oral fat load, the postprandial triglyceridaemia curve was markedly increased in CETP-Tg compared with non-Tg mice (280±30 versus 190±20 mg/dl per 6 h respectively, P<0.02). No differences in intestinal fat absorption and VLDL (very-low-density lipoprotein) secretion rates were observed. Kinetic studies of double-labelled chylomicron-like EMs (emulsions) showed that both [3H]triolein and [14C]cholesteryl oleate FCRs (fractional clearance rates) were significantly reduced (∼20%) in CETP-Tg mice. Furthermore, TAG from lipid EM pre-incubated with CETP-Tg plasma had plasma clearance and liver uptake significantly lower than the non-Tg plasma-treated lipid EM. In addition, reductions in post-heparin plasma LPL (lipoprotein lipase) activity (50%) and adipose tissue mRNA abundance (39%) were verified in CETP-Tg mice. Therefore we conclude that CETP expression in Tg mice delays plasma clearance and liver uptake of TAG-rich lipoproteins by two mechanisms: (i) transferring TAG to HDLs and increasing CE content of the remnant particles and (ii) by diminishing LPL expression. These findings show that the level of CETP expression can influence the responsiveness to dietary fat and may lead to fat intolerance.

scholarly journals Effect of unesterified cholesterol on the activity of cholesteryl ester transfer protein

1994 ◽  
Vol 304 (2) ◽  
pp. 423-430 ◽  
Author(s):  
O V Rajaram ◽  
R Y S Chan ◽  
W H Sawyer
Keyword(s):  
High Density Lipoprotein ◽  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Density Lipoprotein ◽  
High Density ◽  
Reverse Direction ◽  
Unesterified Cholesterol ◽  
Excimer Fluorescence ◽  
Transfer Protein ◽  
Donor And Acceptor

Cholesteryl ester transfer protein (CETP) catalyses the transfer of cholesteryl ester from high-density lipoprotein to triacylglycerol-rich lipoproteins and the transfer of triacylglycerols in the reverse direction. The activity of CETP has been studied using a continuous fluorescence assay which measures the excimer fluorescence of cholesteryl 1-pyrene decanoate in a synthetic donor microemulsion as the indicator of cholesteryl ester transfer. Emulsions were composed of cholesteryl oleate and egg phosphatidylcholine and had an average particle size of 14 +/- 1 nm as calculated from the molar volume of the components. The effect of changing the physical state of the emulsion surface was examined by including unesterified cholesterol in the donor and acceptor particles. The rate of CETP-induced transfer of the fluorescent cholesteryl ester between microemulsion particles increased when unesterified cholesterol was present at concentrations up to 17 mol% relative to phospholipid. The presence of cholesterol also changed the exchange kinetics from an apparent single-exponential to a double-exponential phenomenon. Binding of CETP to the emulsion surface was accompanied by an enhancement of fluorescence which was used to measure the binding equilibria. The enhancement of exchange due to the presence of cholesterol did not correlate with any increased binding of CETP to the emulsion surface. The presence of unesterified cholesterol in the donor did not affect the rate of transfer of the fluorescent cholesteryl ester when unlabelled emulsion was replaced by high-density lipoprotein as the acceptor. The studies demonstrate the use of microemulsions of defined size and composition for the study of the mechanism of action of CETP.

Prevalence and phenotypic spectrum of cholesteryl ester transfer protein gene mutations in Japanese hyperalphalipoproteinemia

2003 ◽  
Vol 166 (1) ◽  
pp. 177-185 ◽  
Author(s):  
Takao Maruyama ◽  
Naohiko Sakai ◽  
Masato Ishigami ◽  
Ken-ichi Hirano ◽  
Takeshi Arai ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Protein Gene ◽  
Gene Mutations ◽  
Transfer Protein ◽  
Phenotypic Spectrum
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