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Acta Physiologica 2010; Volume 200, Supplement 678 Part II
Belgian Society for Fundamental and Clinical Physiology and Pharmacology, Autumn Meeting 2010
10/16/2010-10/16/2010
Université Libre de Bruxelles, Brussels, Belgium
DOPAMINERGIC NEURONS OF SYSTEM XC- DEFICIENT MICE ARE HIGHLY PROTECTED AGAINST 6-OHDA INDUCED TOXICITY
Abstract number: O-03
Massie1 A., Schallier1 A., Kim2 S-W., Fernando3 R., Kobayashi4 S., Beck5 H., De Bundel1 D., Vermoesen1 K., Bannai4 S., Smolders1 I., Conrad6 M., Plesnila2 N., Sato4 H., Michotte1 Y.
1Department of Pharmaceutical Chemistry and Drug Analysis, Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium;
2Royal College of Surgeons in Ireland (RCSI), 123 St. Stephens Green, Dublin 2, Ireland;
3Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden;
4Department of Food and Applied Life Sciences, Faculty of Agriculture, Yamagata University, Tsuruoka, Yamagata 997-8555, Japan.
5Walter Brendel Center of Experimental Medicine, Ludwig-Maximilians-University, Marchioninistr. 27, 81377 Munich, Germany;
6Helmholtz Center Munich, Institute of Clinical Molecular Biology and Tumor Genetics, Marchioninistr. 25, 81377 Munich, Germany.
Malfunctioning of system xc-, responsible for exchanging intracellular glutamate for extracellular cystine, can cause oxidative stress as well as excitotoxicity, both important phenomenons in the pathogenesis of Parkinson's disease. Although cystine that is imported via system xc-, is reduced to cysteine which is the rate-limiting substrate in the synthesis of glutathione, deletion of xCT (xCT-/-), the specific subunit of system xc-, did not result in decreased glutathione levels in striatum. Accordingly, no signs of increased oxidative stress could be observed in striatum or substantia nigra of xCT-/- mice. In sharp contrast to the expectations, xCT-/- mice were less susceptible to 6-OHDA-induced neurodegeneration in the substantia nigra pars compacta. This reduced sensitivity to a Parkinson's disease inducing toxin, might be related to the significantly reduced striatal extracellular glutamate levels that were observed in mice lacking xCT. The current data point towards system xc- as a possible target for the development of new pharmacotherapies for the treatment of Parkinson's disease and emphasizes the need to continue the search for specific ligands for system xc-.
To cite this abstract, please use the following information:
Acta Physiologica 2010; Volume 200, Supplement 678 Part II :O-03