Effects of lipopolysaccharide on glial phenotype and activity of glutamate transporters: Evidence for delayed up-regulation and redistribution of GLT-1

O'Shea, Ross D., Lau, Chew L., Farso, Mark C. and Pow, David V. (2006) Effects of lipopolysaccharide on glial phenotype and activity of glutamate transporters: Evidence for delayed up-regulation and redistribution of GLT-1. Neurochemistry International, 48 6-7: 604-610. doi:10.1016/j.neuint.2005.12.028


Author O'Shea, Ross D.
Lau, Chew L.
Farso, Mark C.
Pow, David V.
Title Effects of lipopolysaccharide on glial phenotype and activity of glutamate transporters: Evidence for delayed up-regulation and redistribution of GLT-1
Journal name Neurochemistry International   Check publisher's open access policy
ISSN 0197-0186
1872-9754
1359-5032
Publication date 2006-05
Sub-type Article (original research)
DOI 10.1016/j.neuint.2005.12.028
Volume 48
Issue 6-7
Start page 604
End page 610
Total pages 7
Editor E. Sylvester Vizi
Roger F. Butterworth
Place of publication U.K.
Publisher Elsevier
Language eng
Subject 1101 Medical Biochemistry and Metabolomics
1109 Neurosciences
Formatted abstract
Excitatory amino acid transporters (EAATs) are responsible for homeostasis of extracellular l-glutamate, and the glial transporters are functionally dominant. EAAT expression or function is altered in acute and chronic neurological conditions, but little is known about the regulation of EAATs in reactive astroglia found in such neuropathologies. These studies examined the effects of the bacterial endotoxin lipopolysaccharide (LPS) on glial EAATs in vitro. The effects of LPS (1 μg/ml, 24-72 h) on EAAT activity and expression were examined in primary cultures of mouse astrocytes. [3H]d-aspartate uptake increased to 129% of control by 72 h treatment with LPS. Saturation analysis revealed that apparent Km was unchanged whilst Vmax was significantly increased to 172% of control by 72 h LPS treatment. Biotinylation and Western blotting indicated that cell-surface expression of GLT-1 was significantly elevated (146% control) by LPS treatment whereas GLAST expression was unchanged. Confocal analyses revealed that LPS treatment resulted in cytoskeletal changes and stellation of astrocytes, with rearrangement of F-actin (as shown by phalloidin labelling). Immunocytochemistry revealed clustering of GLAST, and increased expression and redistribution of GLT-1 to the cell-surface following treatment with LPS. Similar experiments were conducted in microglia, where LPS (50 ng/ml) was found to up-regulate expression of GLT-1 at 24 and 72 h in concert with cytoskeletal changes accompanying activation. These findings suggest an association of cytoskeletal changes in glia with EAAT activity, with the predominant adaptation involving up-regulation and redistribution of GLT-1.
© 2006 Elsevier Ltd. All rights reserved.
Keyword Actins
Newborn animals
Aspartic acid
Astrocytes
Western blotting
Cultured cells
Cytoskeleton
Excitatory amino acid transporter 1
Excitatory amino acid transporter 2
Immunohistochemistry
Lipopolysaccharides
Mice
Mice, inbred C57BL
Microglia
Neuroglia
Q-Index Code C1
Additional Notes Issue May/Jun 2006

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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