| An apolipoprotein E4 fragment affects matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1 and cytokine levels in brain cell lines. | |
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MedLine Citation:
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PMID: 22445724 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Apolipoprotein (apo) E4 isoform, a major risk factor for Alzheimer disease (AD), is more susceptible to proteolysis than apoE2 and apoE3 isoforms. ApoE4 fragments have been found in AD patients' brain. In the present study, we examined the effect of full-length apoE4 and apoE4 fragments apoE4[Δ(186-299)] and apoE4[Δ(166-299)] on inflammation in human neuroblastoma SK-N-SH and human astrocytoma SW-1783 cells. Western blot and zymography analysis showed that treatment of SK-N-SH cells with apoE4[Δ(186-299)], but not full-length apoE4 or the shorter apoE4[Δ(166-299)] fragment, leads to increased extracellular levels of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1). Real-time PCR showed that interleukin (IL)-1β gene expression is also increased in SK-N-SH cells treated with apoE4[Δ(186-299)]. Treatment of SK-N-SH cells with IL-1β leads to increased MMP9 and TIMP1 extracellular levels, suggesting that the induction of IL-1β may be the mechanism by which apoE4[Δ(186-299)] regulates MMP9 and TIMP1 levels in these cells. In contrast to SK-N-SH cells, treatment of SW-1783 cells with apoE4[Δ(186-299)], and to a lesser extent with apoE4, leads to increased TIMP1 extracellular levels without affecting MMP9 levels. Additionally, apoE4[Δ(186-299)] leads to decreased IL-10 gene expression in SK-N-SH cells, whereas both apoE4 and apoE4[Δ(186-299)] lead to decreased TNFα gene expression without affecting IL-1β and IL-10 gene expression in SW-1783 cells. Overall, our findings indicate that a specific apoE4 fragment (apoE4[Δ(186-299)]), with molecular mass similar that of apoE4 fragments detected in AD patients' brain, can influence the level of inflammatory molecules in brain cell lines. It is possible that these phenomena contribute to AD pathogenesis. |
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Authors:
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I Dafnis; A K Tzinia; E C Tsilibary; V I Zannis; A Chroni |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-03-14 |
Journal Detail:
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Title: Neuroscience Volume: 210 ISSN: 1873-7544 ISO Abbreviation: Neuroscience Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-05-21 Completed Date: 2012-09-21 Revised Date: 2013-05-22 |
Medline Journal Info:
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Nlm Unique ID: 7605074 Medline TA: Neuroscience Country: United States |
Other Details:
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Languages: eng Pagination: 21-32 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved. |
Affiliation:
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National Center for Scientific Research Demokritos, Institute of Biology, Agia Paraskevi, Athens 15310, Greece. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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metabolism Apolipoprotein E4 / metabolism, pharmacology* Astrocytes / drug effects, metabolism Blotting, Western Brain / drug effects*, metabolism Cell Line, Tumor Cytokines / drug effects, metabolism* Humans Inflammation / metabolism Matrix Metalloproteinase 9 / drug effects, metabolism* Neurons / drug effects, metabolism Peptide Fragments / metabolism, pharmacology Real-Time Polymerase Chain Reaction Tissue Inhibitor of Metalloproteinase-1 / drug effects, metabolism* Transfection |
| Grant Support | |
ID/Acronym/Agency:
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HL68216/HL/NHLBI NIH HHS; R01 HL068216-09/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoprotein E4; 0/Cytokines; 0/Peptide Fragments; 0/Tissue Inhibitor of Metalloproteinase-1; EC 3.4.24.35/Matrix Metalloproteinase 9 |
| Comments/Corrections | |
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