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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

Journal Article


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.

UOW Authors


  •   Nguyen, Khoa T D. (external author)
  •   Shin, Jae-Won (external author)
  •   Rae, Caroline (external author)
  •   Nanitsos, Ellas K. (external author)
  •   Acosta, Grabriela B. (external author)
  •   Pow, David V. (external author)
  •   Buljan, Vlado (external author)
  •   Bennett, Maxwell R. (external author)
  •   Else, Paul
  •   Balcar, Vladimir J. (external author)

Publication Date


  • 2009

Citation


  • 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.

Scopus Eid


  • 2-s2.0-69049118012

Ro Metadata Url


  • http://ro.uow.edu.au/hbspapers/2307

Number Of Pages


  • 7

Start Page


  • 1767

End Page


  • 1774

Volume


  • 34

Issue


  • 10

Place Of Publication


  • http://springerlink.metapress.com/content/010275g2x48uh500/fulltext.pdf

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.

UOW Authors


  •   Nguyen, Khoa T D. (external author)
  •   Shin, Jae-Won (external author)
  •   Rae, Caroline (external author)
  •   Nanitsos, Ellas K. (external author)
  •   Acosta, Grabriela B. (external author)
  •   Pow, David V. (external author)
  •   Buljan, Vlado (external author)
  •   Bennett, Maxwell R. (external author)
  •   Else, Paul
  •   Balcar, Vladimir J. (external author)

Publication Date


  • 2009

Citation


  • 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.

Scopus Eid


  • 2-s2.0-69049118012

Ro Metadata Url


  • http://ro.uow.edu.au/hbspapers/2307

Number Of Pages


  • 7

Start Page


  • 1767

End Page


  • 1774

Volume


  • 34

Issue


  • 10

Place Of Publication


  • http://springerlink.metapress.com/content/010275g2x48uh500/fulltext.pdf