Rottlerin Inhibits (Na(+), K (+))-ATPase Activity in Brain Tissue and Alters D: -Aspartate Dependent Redistribution of Glutamate Transporter GLAST in Cultured Astrocytes.

NGUYEN KT; SHIN JW; RAE C; NANITSOS EK; ACOSTA GB; POW DV; BULJAN V; BENNETT MR,; ELSE PL; BALCAR VJ.

Neurochemical research

Kluwer Academic/Plenum Publishers

Lugar: United States; Año: 2009 vol. 34 p. 1767 - 1774

0364-3190

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