NDLI: Rottlerin Inhibits (Na$^{+}$, K$^{+}$)-ATPase Activity in Brain Tissue and Alters d-Aspartate Dependent Redistribution of Glutamate Transporter GLAST in Cultured Astrocytes

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Rottlerin Inhibits (Na$^{+}$, K$^{+}$)-ATPase Activity in Brain Tissue and Alters d-Aspartate Dependent Redistribution of Glutamate Transporter GLAST in Cultured Astrocytes

Content Provider	Springer Nature Link
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.
Copyright Year	2009
Abstract	The naturally occurring toxin rottlerin has been used by other laboratories as a specific inhibitor of protein kinase C-delta (PKC-δ) to obtain evidence that the activity-dependent distribution of glutamate transporter GLAST is regulated by PKC-δ 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-δ-catalysed phosphorylation in the process.
Starting Page	1767
Ending Page	1774
Page Count	8
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	34
Issue Number	10
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2009-06-03
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	(Na$^{+}$, K$^{+}$)-dependent ATPase Protein kinase C (PKC) inhibitors GLAST (EAAT1) Uptake of Rb$^{+}$ Regulation of glutamate transport Neurology Biochemistry Neurosciences
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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