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Titolo:
HIGH-AFFINITY SATURABLE UPTAKE OF OXIDIZED LOW-DENSITY-LIPOPROTEIN BYMACROPHAGES FROM MICE LACKING THE SCAVENGER RECEPTOR CLASS-A TYPE I II/
Autore:
LOUGHEED M; LUM CM; LING WH; SUZUKI H; KODAMA T; STEINBRECHER U;
Indirizzi:
UNIV BRITISH COLUMBIA,DEPT MED,3300-950 W 10TH AVE VANCOUVER BC V5Z 4E3 CANADA UNIV BRITISH COLUMBIA,DEPT MED VANCOUVER BC V5Z 4E3 CANADA UNIV TOKYO,ADV SCI & TECHNOL RES CTR,DEPT MOL BIOL & MED TOKYO 153 JAPAN
Titolo Testata:
The Journal of biological chemistry
fascicolo: 20, volume: 272, anno: 1997,
pagine: 12938 - 12944
SICI:
0021-9258(1997)272:20<12938:HSUOOL>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
MOUSE PERITONEAL-MACROPHAGES; NONENZYMATICALLY GLYCOSYLATED PROTEINS; HERITABLE HYPERLIPIDEMIC RABBIT; HUMAN MONOCYTE MACROPHAGES; ALDEHYDE-MODIFIED PROTEINS; OXIDATIVELY MODIFIED LDL; CORONARY HEART-DISEASE; VITAMIN-E CONSUMPTION; HAMSTER OVARY CELLS; ENDOTHELIAL-CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
84
Recensione:
Indirizzi per estratti:
Citazione:
M. Lougheed et al., "HIGH-AFFINITY SATURABLE UPTAKE OF OXIDIZED LOW-DENSITY-LIPOPROTEIN BYMACROPHAGES FROM MICE LACKING THE SCAVENGER RECEPTOR CLASS-A TYPE I II/", The Journal of biological chemistry, 272(20), 1997, pp. 12938-12944

Abstract

Oxidation of low density lipoproteins (LDL) has been implicated as a causal factor in the pathogenesis of atherosclerosis. Oxidized LDL hasbeen found to exhibit numerous potentially atherogenic properties in vitro, including receptor mediated uptake by macrophages. Oxidized LDLis a ligand for the class A scavenger receptor type I/II (SR-AI/II), but cross-competition studies with cultured macrophages suggested thatthere is an additional receptor(s) that is specific for oxidized LDL and that does not interact with acetyl LDL or other chemically modified LDL. A number of macrophage membrane proteins, including CD36, Fc gamma RII-B2, scavenger receptor BI, and macrosialin/CD68, have been found to bind to oxidized LDL in vitro and have been proposed as candidate oxidized LDL receptors, However, because of overlapping ligand specificity with the SR-AI/II, it has been difficult to evaluate the relative importance of these proteins in the uptake of oxidized LDL by macrophages, In the present report, we have studied the uptake and degradation of oxidized LDL by macrophages from mice in which the SR-AI/II gene had been disrupted, The uptake of acetyl LDL was reduced by more than 80% in macrophages from scavenger receptor knockout mice, confirmingthat most of the uptake of acetyl LDL by macrophages can be attributed to this receptor, In contrast, the uptake of extensively oxidized LDL was reduced by only 30% and showed high affinity, saturable uptake with apparent K-m of about 5 mu g/ml, similar to that of the SR-AI/II, This indicates that about 70% of the uptake of oxidized LDL in macrophages is attributable to an alternate oxidized LDL receptor(s), In contrast to findings reported with CD36, mildly oxidized LDL was internalized much more slowly than extensively oxidized LDL, Unlabeled oxidizedLDL, polyinosinic acid, phosphatidylserine-rich liposomes, and LDL orbovine albumin modified by fatty acid oxidation products were effective competitors for the uptake of radioiodinated oxidized LDL by macrophages from knockout mice, whereas acetyl LDL and malondialdehyde-modified LDL were relatively poor competitors, This ligand specificity differs from that of CD36-related (class B) scavenger receptors but is similar to the reported specificity of macrosialin/CD68 in ligand blots, However, the rate of uptake of oxidized LDL by knockout macrophages was not increased by phorbol ester or in thioglycollate-elicited macrophages, both of which are expected to increase the amount of macrosialinon the cell surface, In macrophages from SR-AI/II knockout mice, ligand blots of membrane proteins with iodinated, oxidized, or acetylated LDL revealed several bands, with apparent molecular size on SDS-polyacrylamide gel electrophoresis of 60, 94, 124, and 210 kDa, but none of the bands were specific for oxidized LDL, These results provide directevidence that a receptor other than SR-AI/II is responsible for most of the uptake of oxidized LDL in murine macrophages, but further studies are needed to identify the receptor(s) involved.

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Documento generato il 18/02/20 alle ore 05:00:18