Model class A and class L peptides increase the production of apoA-I-containing lipoproteins in HepG2 cells.
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 (35)S-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 (3)H-labeled phospholipids by 140% and (14)C-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 prebeta- as well as alpha-HDL. This study suggests that increased secretion of phospholipids and apoA-I and the formation of prebeta-HDL particles might contribute to the antiatherogenic properties of these peptides.
Department of Medicine, Biochemistry, and Molecular Genetics, and Atherosclerosis Research Unit, University of Alabama at Birmingham, Birmingham, AL 35294, USA. ndashti@uab.edu
Nassrin
N
Dashti
Geeta
G
Datta
Medha
M
Manchekar
Manjula
M
Chaddha
G M
GM
Anantharamaiah
D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000378:metabolism; D001161:Arteriosclerosis / Q000188:drug therapy; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000096:biosynthesis*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D017433:Protein Structure, Secondary; D015854:Up-Regulation / Q000187:drug effects
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008074:Lipoproteins; D010455:Peptides; D010743:Phospholipids; D002784:Cholesterol