Publications (2)2.13 Total impact
Article: Interaction of CETP inhibitory peptide and lipoprotein substrates in cholesteryl ester transfer assay: relationship between association properties and inhibitory activities.[show abstract] [hide abstract]
ABSTRACT: In a previous study, CETP inhibitory peptide (3 kDa) was isolated from hog plasma. The peptide, synthesized chemically according to the amino acid sequence of the 3-kDa peptide (designated P28), showed CETP inhibitory activity both in vitro and in vivo ICho et al. (1998) Biochim. Biophys. Acta 1391, 133-144]. We report herein further unique features of P28 when it was associated with the cholesteryl ester (CE)-donor and -acceptor lipoproteins. Lipoprotein substrates with P28 present in both HDL (as a CE-donor) and LDL (as a CE-acceptor) served as poor substrates, with CE-transfer activity decreased up to 60% compared to normal substrates without P28. P28 was found to be located in HDL fractions of hog plasma and showed the same electromobility as that visualized by PAGE on 7% polyacrylamide gel under nondenaturing conditions. Addition of apolipoprotein A-1 (apoA-1) or apoB antibody to a normal CE-transfer mixture did not alter CE-transfer activity. However, addition of apoA-1 or -B antibody to a CETP-inhibition mixture decreased the inhibitory activity of P28 by ca. 20%. Western blot analysis revealed that P28 was associated only with human and hog HDL among several lipoproteins purified from human, hog, and rabbit. CETP-inhibition assays with various lipoprotein substrates revealed that P28 exhibited substrate-specific inhibitory activity. The inhibitory activity of P28 was highly dependent on the type of lipoprotein substrate (whether CE-donor or -acceptor); P28 inhibited CE transfer from HDL to LDL, but it did not inhibit CE transfer from HDL to HDL.Lipids 08/2002; 37(7):641-6. · 2.13 Impact Factor
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ABSTRACT: A peptide that inhibits the human cholesteryl ester transfer protein (CETP) was isolated from hog plasma by ultracentrifugation, two sequential column chromatographies and electroelution from gels. Molecular weight of the peptide was determined to be approximately 3 kDa on the SDS–PAGE. The peptide contained 28 amino acids with an identical sequence to the amino terminus of hog apolipoprotein-CIII except two amino acid residues: –Pro–Glu– at the fifth and sixth amino acids from the amino terminus in the isolated peptide, in contrast to –Leu–Leu– in hog apo-CIII. A peptide synthesized chemically according to the amino acid sequence of the peptide (designated P28) showed approximately the same degree of CETP inhibitory activity as the isolated peptide. Synthetic peptides with different number of amino acids were also tested for CETP inhibition. Among the peptides, the one with 20 amino acid residues (P20) from the amino terminus showed the highest inhibitory activity against the CETP. The peptide appeared to be associated with the hog high-density lipoproteins (HDL), as determined by immunoblot analysis using antibody against P28. The CETP-inhibitory activity of the peptide was examined in vivo using diet-induced hypercholesterolemic rabbits. When the peptide was injected into the rabbits (7–9 mg/kg body weight), approximately 75% CETP activity disappeared from the plasma in 1 h after the injection and the effect lasted up to 30 h. The inhibition of CETP in vivo led to a concomitant decrease in total plasma cholesterol level up to 30% and an increase in the level of HDL-cholesterol up to 32%. The cholesterol concentrations in the rabbit plasma gradually recovered to the initial level after 48 h.Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism.