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Titolo:
PHENOTYPE-DEPENDENT DIFFERENCES IN APOLIPOPROTEIN-E METABOLISM AND INCHOLESTEROL HOMEOSTASIS IN HUMAN MONOCYTE-DERIVED MACROPHAGES
Autore:
CULLEN P; CIGNARELLA A; BRENNHAUSEN B; MOHR S; ASSMANN G; VONECKARDSTEIN A;
Indirizzi:
UNIV MUNSTER,INST ARTERIOSKLEROSEFORSCH,DOMAGKSTR 3 D-48149 MUNSTER GERMANY UNIV MUNSTER,INST KLIN CHEM & LAB MED D-48149 MUNSTER GERMANY
Titolo Testata:
The Journal of clinical investigation
fascicolo: 8, volume: 101, anno: 1998,
pagine: 1670 - 1677
SICI:
0021-9738(1998)101:8<1670:PDIAMA>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
BONE-MARROW TRANSPLANTATION; E-DEFICIENT MICE; E POLYMORPHISM; DENSITY-LIPOPROTEINS; APOPROTEIN-E; EXPRESSION; SECRETION; PLASMA; EFFLUX; ATHEROSCLEROSIS;
Keywords:
APOE POLYMORPHISM; CHOLESTEROL EFFLUX; ATHEROSCLEROSIS; HUMAN MONOCYTE-DERIVED MACROPHAGES; ALZHEIMERS DISEASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
45
Recensione:
Indirizzi per estratti:
Citazione:
P. Cullen et al., "PHENOTYPE-DEPENDENT DIFFERENCES IN APOLIPOPROTEIN-E METABOLISM AND INCHOLESTEROL HOMEOSTASIS IN HUMAN MONOCYTE-DERIVED MACROPHAGES", The Journal of clinical investigation, 101(8), 1998, pp. 1670-1677

Abstract

In this study, we investigated the impact of the common apoE polymorphism on apoE metabolism and cholesterol homeostasis in monocyte-derived macrophages isolated from E2/2, E3/3, and E4/4 subjects. Unloaded cells of all genotypes contained similar amounts of free cholesterol, cholesteryl ester, and apoE mRNA. E3/3 cells secreted 77 and 30% more apoE than E2/2 or E4/4 cells, respectively. Pulse-chase studies confirmed that the apoE secretion rate was greatest in E3/3 and least in E2/2 cells and showed that a portion of apoE2, but not apoE3 or apoE4, was degraded intracellulary. Surface binding of apoE was greatest in E4/4 cells, as revealed by heparinase treatment. On cholesterol loading with acetylated LDL, apoE mRNA levels and protein secretion rose most in E4/4 and least in E2/2 cells. Cholesterol and cholesteryl ester content, however, rose most in E2/2 and least in E3/3 cells. Incubations with H-3-cholesterol-labeled acetylated LDL revealed that E2/2 cells weremost efficient at secreting cholesterol. The greatest reuptake of H-3-cholesterol-rich particles was from E4/4 macrophage-conditioned media. Thus, E2/2 macrophages, despite a low apoE secretion rate, are protected from cholesterol storage by apoE-mediated cholesterol efflux. In E3/3 macrophages, cholesterol accumulation is lessened by a high basalapoE secretion rate. E4/4 macrophages secrete the most apoE but lack effective net cholesterol efflux due to enhanced surface binding and reuptake of cholesterol-rich particles.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/02/20 alle ore 14:18:17