Rottlerin inhibits (Na+, K+)-ATPase Activity in brain tissue and alters d-Aspartate dependent redistribution of glutamate transporter GLAST in cultured astrocytes

Nguyen, Khoa T. D., Shin, Jae-Won, Rae, Caroline, Nanitsos, Ellas K., Acosta, Gabriela B., Pow, David V., Buljan, Vlado, Bennett, Maxwell R., Else, Paul L. and Balcar, Vladimir J. (2009) Rottlerin inhibits (Na+, K+)-ATPase Activity in brain tissue and alters d-Aspartate dependent redistribution of glutamate transporter GLAST in cultured astrocytes. Neurochemical Research, 34 10: 1767-1774. doi:10.1007/s11064-009-9996-6


Author Nguyen, Khoa T. D.
Shin, Jae-Won
Rae, Caroline
Nanitsos, Ellas K.
Acosta, Gabriela B.
Pow, David V.
Buljan, Vlado
Bennett, Maxwell R.
Else, Paul L.
Balcar, Vladimir J.
Title Rottlerin inhibits (Na+, K+)-ATPase Activity in brain tissue and alters d-Aspartate dependent redistribution of glutamate transporter GLAST in cultured astrocytes
Journal name Neurochemical Research   Check publisher's open access policy
ISSN 0364-3190
Publication date 2009-10
Year available 2009
Sub-type Article (original research)
DOI 10.1007/s11064-009-9996-6
Volume 34
Issue 10
Start page 1767
End page 1774
Total pages 8
Editor Abel Lajtha
Place of publication New York, N.Y., U. S. A.
Publisher Springer New York LLC
Collection year 2010
Language eng
Subject 110902 Cellular Nervous System
C1
Abstract The naturally occurring toxin rottlerin has been used by other laboratories as a specific inhibitor of protein kinase C-delta (PKC-delta) to obtain evidence that the activity-dependent distribution of glutamate transporter GLAST is regulated by PKC-delta mediated phosphorylation. Using immunofluorescence labelling for GLAST and deconvolution microscopy we have observed that D-aspartate-induced redistribution of GLAST towards the plasma membranes of cultured astrocytes was abolished by rottlerin. In brain tissue in vitro, rottlerin reduced apparent activity of (Na+, K+)-dependent ATPase (Na+, K+-ATPase) and increased oxygen consumption in accordance with its known activity as an uncoupler of oxidative phosphorylation ("metabolic poison"). Rottlerin also inhibited Na+, K+-ATPase in cultured astrocytes. As the glutamate transport critically depends on energy metabolism and on the activity of Na+, K+-ATPase in particular, we suggest that the metabolic toxicity of rottlerin and/or the decreased activity of the Na+, K+-ATPase could explain both the glutamate transport inhibition and altered GLAST distribution caused by rottlerin even without any involvement of PKC-delta-catalysed phosphorylation in the process.
Keyword (Na+, K+)-dependent ATPase
Protein kinase C (PKC) inhibitors
GLAST (EAAT1)
Uptake of Rb+
Regulation of glutamate transport
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
2010 Higher Education Research Data Collection
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 03 Sep 2009, 07:41:32 EST by Mr Andrew Martlew on behalf of UQ Centre for Clinical Research