J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M400251-JLR200 on August 1, 2004

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Journal of Lipid Research, Vol. 45, 1919-1928, October 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Model class A and class L peptides increase the production of apoA-I-containing lipoproteins in HepG2 cells

Nassrin Dashti1, Geeta Datta, Medha Manchekar, Manjula Chaddha and G. M. Anantharamaiah1,2

Department of Medicine, Biochemistry, and Molecular Genetics, and Atherosclerosis Research Unit, University of Alabama at Birmingham, Birmingham, AL 35294

1 To whom correspondence should be addressed. e-mail: ndashti{at}uab.edu (N.D.); ananth{at}uab.edu (G.M.A.)

Class A peptides inhibit atherosclerosis and protect cells from class L peptide-mediated lysis. Because the cytolytic process is concentration dependent, we hypothesized that at certain concentrations both classes of peptides exert similar effect(s) on cells. To test this hypothesis, we studied the effects of a class L peptide (18L = GIKKFLGSIWKFIKAFVG) and a class A peptide, 18A-Pro-18A (18A = DWLKAFYDKVAEKLKEAF) (37pA), on apolipoprotein and lipoprotein production in HepG2 cells. Secretion of 35S-labeled apolipoprotein A-I (apoA-I) was stimulated by both 18L (110%) and 37pA (135%) at 10 and 20 nM of peptides, respectively. Both peptides enhanced the secretion of 3H-labeled phospholipids by 140% and 14C-labeled HDL-cholesterol (HDL-C) by 35% but had no significant effect on the total cholesterol mass or secretion.

These results indicate that class L and class A peptides cause redistribution of cholesterol among lipoproteins in favor of HDL-C. Both peptides remodeled apoA-I-containing particles forming preß- as well as {alpha}-HDL. This study suggests that increased secretion of phospholipids and apoA-I and the formation of preß-HDL particles might contribute to the antiatherogenic properties of these peptides.

Abbreviations: apoA-I, apolipoprotein A-I; HDL-C, high density lipoprotein-cholesterol; LDH, lactic dehydrogenase; PL/C, phospholipid-to-cholesterol ratio; Rf, relative mobility

Supplementary key words apolipoprotein A-I • apolipoprotein B • high density lipoprotein metabolism • low density lipoprotein metabolism • triglyceride secretion • cholesterol secretion • phospholipid secretion • apolipoprotein synthesis • apolipoprotein secretion • hepatocytes • atherosclerosis


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