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Titolo:
Biochemical analysis of cell-derived apoE3 particles active in stimulatingneurite outgrowth
Autore:
DeMattos, RB; Rudel, LL; Williams, DL;
Indirizzi:
SUNY Stony Brook, Med Ctr, Dept Pharmacol Sci, Stony Brook, NY 11794 USA SUNY Stony Brook Stony Brook NY USA 11794 Sci, Stony Brook, NY 11794 USA Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol Comparat Med, Winston Salem, NC 27103 USA Wake Forest Univ Winston Salem NC USA 27103 , Winston Salem, NC 27103 USA
Titolo Testata:
JOURNAL OF LIPID RESEARCH
fascicolo: 6, volume: 42, anno: 2001,
pagine: 976 - 987
SICI:
0022-2275(200106)42:6<976:BAOCAP>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
DENSITY-LIPOPROTEIN RECEPTOR; HEPARAN-SULFATE PROTEOGLYCANS; HUMAN APOLIPOPROTEIN-E; E MESSENGER-RNA; CENTRAL NERVOUS-SYSTEM; AMYLOID-BETA-PEPTIDE; ALZHEIMERS-DISEASE; A-I; PERIPHERAL-TISSUES; CEREBROSPINAL-FLUID;
Keywords:
Alzheimer's disease; HDL; LDL receptor; LDL receptor-related protein; neurodegeneration; cholesterol;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
68
Recensione:
Indirizzi per estratti:
Indirizzo: Williams, DL Washington Univ, Sch Med, Ctr Study Nervous Syst Injury, 660 S Euclid Ave,Box 8111, St Louis, MO 63110 USA Washington Univ 660 S Euclid Ave,Box 8111 St Louis MO USA 63110
Citazione:
R.B. DeMattos et al., "Biochemical analysis of cell-derived apoE3 particles active in stimulatingneurite outgrowth", J LIPID RES, 42(6), 2001, pp. 976-987

Abstract

Susceptibility to the development of late-onset Alzheimer's disease is increased for individuals harboring one or more apolipoprotein E4 (apoE4) alleles. Although several isoform-specific effects of apoE have been identified, the relationship between biochemical function and risk factor assessment is unknown. Our previous studies showed that a physiologically relevant cell-derived apoE3 particle stimulates neurite outgrowth in an isoform-specific manner. In an attempt to delineate the biochemical mechanism responsible for the stimulatory effects of apoE3 on neurite outgrowth, we performed a detailed physical characterization of cell-derived apoE3 and apoE4 par tides. Immunoaffinity chromatography followed by SDS-PAGE illustrated homogeneity in protein content (apoE > 95%), The affinity-purified particles contained phospholipid and 1 mol of cholesterol per mole of apoE but no core lipids. Nondenaturing gradient gel electrophoresis identified two major particle populations with hydrated diameters of 8.0 and 9.2 nm. Neurite outgrowth assays performed with the affinity-purified particles resulted in similar isoform-specific differences as seen previously apoE3 stimulatory and apoE4 neutral. Interestingly, we did not observe a reduction in apoE medium concentrations over the duration of the neurite outgrowth assays, suggesting Little or no endocytic uptake. Ligand blot analysis demonstrated that the affinity-purified apoE particles bind to several Neuro-2a membrane proteins. Western blots of the Neuro-2a membrane proteins indicated that the LDL receptor, gp330, and LR8B might be involved in the apoE-binding event. These results discriminate against the lipid delivery hypothesis and suggest that the biological activity of the phospholipid apoE3 particles may be due to cell surface signaling. - DeMattos, R. B., L. L. Rudel, and D. L. Williams. Biochemical analysis of cell-derived apoE3 particles active in stimulating neurite outgrowth.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 16:00:37