Document Detail


L-serine-mediated release of apolipoprotein E and lipids from microglial cells.
MedLine Citation:
PMID:  14736503     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apolipoprotein E (ApoE), one of the genetic risk factors for Alzheimer's disease, is considered to have a critical role in transporting lipids in the brain. In the present study, we investigated ApoE release in primary rat microglial cultures. Microglial cells released ApoE in response to L-Ser in culture medium, and ApoE-immunoreactivity was detected in granules in the cell periphery and in perinuclear structures. Immunocytochemical studies, immunoblotting, and reverse transcription-polymerase chain reaction (RT-PCR) results all supported the notion that microglial cells are the potential source of ApoE in the brain. L-Ser enhanced ApoE release in a concentration-dependent manner without upregulating ApoE mRNA expression. Astrocytes presumably enhanced production and release of ApoE by microglial cells through secretion of L-Ser. As revealed by gel chromatography, ApoE was secreted as a component of lipoproteins, and L-Ser enhanced release of cholesterol and triglycerides together with ApoE. Activation of microglial cells by lipopolysaccharides and serum resulted in an overall decrease of the ApoE release. These findings suggest that microglial cells are a significant source of lipoproteins containing ApoE in the brain under physiological conditions, and that L-Ser is an important mediator of the neuron-astrocyte-microglia network in the brain.
Authors:
Kohji Mori; Akiko Yokoyama; Lihua Yang; Limin Yang; Nobuji Maeda; Noriaki Mitsuda; Junya Tanaka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental neurology     Volume:  185     ISSN:  0014-4886     ISO Abbreviation:  Exp. Neurol.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-22     Completed Date:  2004-03-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  220-31     Citation Subset:  IM    
Affiliation:
Department of Physiology, School of Medicine, Ehime University, Ehime 791-0295, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apolipoproteins E / biosynthesis,  secretion*
Astrocytes / drug effects,  metabolism,  secretion
Cells, Cultured
Cholesterol / biosynthesis,  secretion
Coculture Techniques
Dose-Response Relationship, Drug
Lipids / biosynthesis,  secretion
Lipoproteins / biosynthesis,  secretion*
Microglia / drug effects*,  metabolism,  secretion*
Prosencephalon / drug effects,  metabolism,  secretion
Rats
Rats, Wistar
Serine / pharmacology*
Triglycerides / biosynthesis,  secretion
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 0/Lipids; 0/Lipoproteins; 0/Triglycerides; 56-45-1/Serine; 57-88-5/Cholesterol

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