Only multimers of a synthetic peptide of human apolipoprotein E are biologically active.
Plasma apolipoprotein E (apoE) is a ligand for the cellular uptake of cholesterol-rich plasma lipoproteins. ApoE also inhibits mitogen-stimulated lymphocyte proliferation and gonadotropin-stimulated ovarian theca/interstitial cell androgen production. To address the mechanism(s) by which apoE is active and to understand its interaction with the target cells, we prepared and examined the inhibitory activity of a series of apoE synthetic peptides. ApoE peptides representing amino acid residues 93-112, 141-155, 161-171, 172-182, and 174-193 were not active in either bioassay. However, specific inhibition of both lymphocyte proliferation and ovarian androgen production was observed with a self-conjugate of peptide-(141-155). Furthermore, a synthesized dimeric peptide representing two repeats of sequence-(141-155) (i.e. (141-155)-(141-155] was active as well. In both bioassays, the inhibition observed was not a result of direct cell killing. Furthermore, these apoE peptides exhibited activities with characteristics that were shared with those of native apoE. The results indicate that amino acid residues 141-155 of apoE are responsible for the biological activity of apoE. Furthermore, the results suggest that dimers or multimers of native apoE may be a biologically important species.
Dyer
C A
CA
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Smith
R S
RS
Curtiss
L K
LK
D000595:Amino Acid Sequence; D000726:Androgen Antagonists; D000728:Androgens / Q000096:biosynthesis; D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008114:Liver Neoplasms, Experimental; D008213:Lymphocyte Activation / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology*; D008934:Mitogens; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis; D011817:Rabbits; D051381:Rats; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D000728:Androgens; D001057:Apolipoproteins E; D008934:Mitogens; D010455:Peptides