An alternate pathway for low density lipoprotein uptake: synthetic peptide models of a conserved anionic domain of apolipoprotein

E. Samuel, R. Dominguez, Timothy S. Burkoth, Tamnfie L.S. Benzinger, Tlelene Auer, Paul A. Monach, Stephen C. Meredith

Research output: Contribution to journalArticlepeer-review

Abstract

We have shown that two lactam-crosslinked synthetic peptide models of a con served, anionic domain (amino acids 40-60) of human apolipoprotein E (apot';) are able to increase the binding and internalization of LDI, to LI)L receptor (LDL-R) and LDL-R related protein (LRP) deficient cells. The increase is as much as 60-fold, and occurs in a conformationally specific manner. In sit crosslinking studies suggest that binding is mediated by a celt surface molecule of Mc=500,000. Preliminary data suggest that preincubation of cells with hap arinase or chlorate does not abrogate this binding, indicating that the binding is not dependent on cell surface glycans. The binding is inhibitable only by LDL, and not by high density lipoproteins, very low density lipoproteins, ox idized LDL, or acetyla.ted LDL. Receptor number, as indicated by maximal LDL binding, is increased 5-fold by preincubation with tumor necrosis factor alpha (TNF-a). The binding is not increased by preincubating cells with lipoprotein deficient serum, and in contrast to traditional lipoprotein receptors such as the LDL-R and LRP, the binding is not calcium dependent. Our data suggest the existence of an alternate pathway for LI)L binding and uptake. independent of the LDL-R, LRP or known scavenger receptors, which is in ducible by proinflammatory cytokines such as TNI-' (. (Supported by Nt/SA #1I:'31 HL09729-01 and CNRU P30-DK 26678-17).

Original languageEnglish
Pages (from-to)A1264
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997

Fingerprint

Dive into the research topics of 'An alternate pathway for low density lipoprotein uptake: synthetic peptide models of a conserved anionic domain of apolipoprotein'. Together they form a unique fingerprint.

Cite this