Linked Life Data

11369806

Source:http://linkedlifedata.com/resource/pubmed/id/11369806

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-5-22
pubmed:abstractText
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 particles. 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2275
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
976-87
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11369806-Apolipoprotein E3, pubmed-meshheading:11369806-Apolipoprotein E4, pubmed-meshheading:11369806-Apolipoproteins E, pubmed-meshheading:11369806-Azo Compounds, pubmed-meshheading:11369806-Blotting, Western, pubmed-meshheading:11369806-Cell Division, pubmed-meshheading:11369806-Cell Line, pubmed-meshheading:11369806-Cell Membrane, pubmed-meshheading:11369806-Chromatography, Affinity, pubmed-meshheading:11369806-Coloring Agents, pubmed-meshheading:11369806-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:11369806-Endocytosis, pubmed-meshheading:11369806-Humans, pubmed-meshheading:11369806-Ligands, pubmed-meshheading:11369806-Lipid Metabolism, pubmed-meshheading:11369806-Neurons, pubmed-meshheading:11369806-Protein Isoforms, pubmed-meshheading:11369806-Signal Transduction
pubmed:year
2001
pubmed:articleTitle
Biochemical analysis of cell-derived apoE3 particles active in stimulating neurite outgrowth.
pubmed:affiliation
Department of Pharmacological Sciences, University Medical Center, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't