| Stable expression and secretion of apolipoproteins E3 and E4 in mouse neuroblastoma cells produces differential effects on neurite outgrowth. | |
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MedLine Citation:
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PMID: 7592957 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previously, we demonstrated in cultured dorsal root ganglion neurons that, in the presence of beta-migrating very low density lipoproteins (beta-VLDL), apolipoprotein (apo) E4, but not apoE3, suppresses neurite outgrowth. In the current studies, murine neuroblastoma cells (Neuro-2a) were stably transfected with human apoE3 or apoE4 cDNA, and the effect on neurite outgrowth was examined. The stably transfected cells secreted nanogram quantities of apoE (44-89 ng/mg of cell protein in 48 h). In the absence of lipoproteins, neurite outgrowth was similar in the apoE3- and apoE4-secreting cells. The apoE4-secreting cells, when incubated with beta-VLDL, VLDL, cerebrospinal fluid lipoproteins (d < 1.21 g/ml), or with triglyceride/phospholipid (2.7:1 (w/w)) emulsions, showed a reduction in the number of neurites/cell, a decrease in neurite branching, and an inhibition of neurite extension, whereas in the apoE3-secreting cells in the presence of a lipid source, neurite extension was increased. Uptake of beta-VLDL occurred to a similar extent in both the apoE3- and apoE4-secreting cells. With low density lipoproteins or with dimyristoylphosphatidylcholine emulsions, either alone or complexed with cholesterol, no differential effect on neurite outgrowth was observed. A slight differential effect was observed with apoE-containing high density lipoproteins. The differential effect of apoE3 and apoE4 in the presence of beta-VLDL was blocked by incubation of the cells with heparinase and chlorate, with lactoferrin, or with receptor-associated protein, all of which prevent the uptake of lipoproteins by the low density lipoprotein receptor-related protein (LRP). The data suggest that the secreted and/or cell surface-bound apoE interact with the lipoproteins and facilitate their internalization via the heparan sulfate proteoglycan-LRP pathway. The mechanism by which apoE3 and apoE4 exert differential effects on neurite outgrowth remains speculative. However, the data suggest that apoE4, which has been shown to be associated with late onset familial and sporadic Alzheimer's disease, may inhibit neuronal remodeling and contribute to the progression of the disease. |
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Authors:
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S Bellosta; B P Nathan; M Orth; L M Dong; R W Mahley; R E Pitas |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 270 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1995 Nov |
Date Detail:
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Created Date: 1995-12-26 Completed Date: 1995-12-26 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 27063-71 Citation Subset: IM |
Affiliation:
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Gladstone Institute of Cardiovascular Disease, University of California, San Francisco 94141-9100, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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etiology Animals Apolipoprotein E3 Apolipoprotein E4 Apolipoproteins E / genetics*, secretion* DNA, Complementary / genetics Gene Expression Humans Lipoproteins, VLDL / pharmacology Liposomes Mice Neurites / drug effects, physiology*, ultrastructure* Neuroblastoma / genetics, secretion, ultrastructure Rabbits Transfection Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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AG13619/AG/NIA NIH HHS; HL41633/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoprotein E3; 0/Apolipoprotein E4; 0/Apolipoproteins E; 0/DNA, Complementary; 0/Lipoproteins, VLDL; 0/Liposomes |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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