Document Detail

An apolipoprotein E4 fragment affects matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1 and cytokine levels in brain cell lines.
MedLine Citation:
PMID:  22445724     Owner:  NLM     Status:  MEDLINE    
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.
I Dafnis; A K Tzinia; E C Tsilibary; V I Zannis; A Chroni
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-14
Journal Detail:
Title:  Neuroscience     Volume:  210     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-21     Completed Date:  2012-09-21     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  21-32     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Alzheimer Disease / metabolism
Apolipoprotein E4 / metabolism,  pharmacology*
Astrocytes / drug effects,  metabolism
Blotting, Western
Brain / drug effects*,  metabolism
Cell Line, Tumor
Cytokines / drug effects,  metabolism*
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*
Grant Support
Reg. No./Substance:
0/Apolipoprotein E4; 0/Cytokines; 0/Peptide Fragments; 0/Tissue Inhibitor of Metalloproteinase-1; EC Metalloproteinase 9

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