Title

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

RIS ID

31332

Publication Details

Nguyen, K. T.D., Shin, J., Rae, C., Nanitsos, E. K., Acosta, G. B., Pow, D. V., Buljan, V., Bennett, M. R., Else, P. L. & Balcar, V. 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.

Abstract

The naturally occurring toxin rottlerin has been used by other laboratories as a specific inhibitor of protein kinase C-delta (PKC-d) to obtain evidence that the activitydependent distribution of glutamate transporter GLAST is regulated by PKC-d mediated phosphorylation. Using immunofluorescence labelling for GLAST and deconvolution microscopy we have observed that D-aspartateinduced 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-d-catalysed phosphorylation in the process.

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Link to publisher version (DOI)

http://dx.doi.org/10.1007/s11064-009-9996-6