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System xc- is an important source of extracellular glutamate and involved in the pathogenesis of several neurological disorders. / Massie, Ann; Van Liefferinge, Joeri; Bentea, Eduard-Mihai; Merckx, Ellen; Demuyser, Thomas; Albertini, Giulia; Sato, Hideyo; Smolders, Ilse Julia.

Conferences on amino-acidergic transmission: Glutamate/GABA and Neuro-Glia-Vascular Interplay in Norm and Pathology, 21-24 May 2014, Krakow, Poland. 2014.

Research output: Chapter in Book/Report/Conference proceedingMeeting abstract (Book)

Harvard

Massie, A, Van Liefferinge, J, Bentea, E-M, Merckx, E, Demuyser, T, Albertini, G, Sato, H & Smolders, IJ 2014, System xc- is an important source of extracellular glutamate and involved in the pathogenesis of several neurological disorders. in Conferences on amino-acidergic transmission: Glutamate/GABA and Neuro-Glia-Vascular Interplay in Norm and Pathology, 21-24 May 2014, Krakow, Poland. Unknown, 21/05/14.

APA

Massie, A., Van Liefferinge, J., Bentea, E-M., Merckx, E., Demuyser, T., Albertini, G., ... Smolders, I. J. (2014). System xc- is an important source of extracellular glutamate and involved in the pathogenesis of several neurological disorders. In Conferences on amino-acidergic transmission: Glutamate/GABA and Neuro-Glia-Vascular Interplay in Norm and Pathology, 21-24 May 2014, Krakow, Poland

Vancouver

Massie A, Van Liefferinge J, Bentea E-M, Merckx E, Demuyser T, Albertini G et al. System xc- is an important source of extracellular glutamate and involved in the pathogenesis of several neurological disorders. In Conferences on amino-acidergic transmission: Glutamate/GABA and Neuro-Glia-Vascular Interplay in Norm and Pathology, 21-24 May 2014, Krakow, Poland. 2014

Author

BibTeX

@inbook{dd65a21b30304f7da86ae25f07471002,
title = "System xc- is an important source of extracellular glutamate and involved in the pathogenesis of several neurological disorders",
abstract = "System xc- or the cystine/glutamate antiporter imports one cystine in exchange for one glutamate molecule. Cystine is intracellularly reduced to cysteine, the rate-limiting building block of glutathione. Malfunctioning of system xc- can thus cause oxidative stress as well as excitotoxicity, important phenomenons in the pathogenesis of Parkinson's disease, epilepsy, multiple sclerosis and many other neurological disorders. However, deletion of xCT (xCT-/- mice) did not affect striatal or hippocampal glutathione levels and no signs of increased oxidative stress were seen in xCT-/- mice. Interestingly, extracellular hippocampal and striatal glutamate levels were decreased by >60{\%} in xCT-/- mice compared to controls. In addition, intrahippocampal perfusion with system xc- inhibitors lowered extracellular glutamate whereas the system xc- activator N-acetylcysteine elevated extracellular glutamate in rat hippocampus, suggesting that system xc- might be an interesting target for pathologies associated with excessive extracellular glutamate release. Indeed, we observed increased expression levels of xCT, the specific subunit of system xc-, in brain samples of rodent models for several neurological disorders as well as patients. To investigate the relevance of this altered expression of xCT, we used xCT-/- mice to study in vivo the effect of system xc- deficiency on the behavioral and/or neurochemical outcome in models for Parkinson's disease, limbic seizures, epilepsy and multiple sclerosis. xCT deletion resulted in protection of the mice in models for Parkinson's disease, limbic seizures and epilepsy. Loss of xCT did not affect the susceptibility of mice in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis. The current data sustain that system xc- is an important source of hippocampal and striatal extracellular glutamate that might become activated in pathological conditions and as such cause accumulation of extracellular glutamate to toxic levels. Inhibition of system xc- might thus represent an innovative strategy for the future development of drugs for the treatment of neurological disorders that are characterized by dysregulated glutamatergic neurotransmission.",
keywords = "system xc-, xCT, glutamate",
author = "Ann Massie and {Van Liefferinge}, Joeri and Eduard-Mihai Bentea and Ellen Merckx and Thomas Demuyser and Giulia Albertini and Hideyo Sato and Smolders, {Ilse Julia}",
year = "2014",
month = "5",
day = "21",
language = "English",
booktitle = "Conferences on amino-acidergic transmission: Glutamate/GABA and Neuro-Glia-Vascular Interplay in Norm and Pathology, 21-24 May 2014, Krakow, Poland",

}

RIS

TY - CHAP

T1 - System xc- is an important source of extracellular glutamate and involved in the pathogenesis of several neurological disorders

AU - Massie, Ann

AU - Van Liefferinge, Joeri

AU - Bentea, Eduard-Mihai

AU - Merckx, Ellen

AU - Demuyser, Thomas

AU - Albertini, Giulia

AU - Sato, Hideyo

AU - Smolders, Ilse Julia

PY - 2014/5/21

Y1 - 2014/5/21

N2 - System xc- or the cystine/glutamate antiporter imports one cystine in exchange for one glutamate molecule. Cystine is intracellularly reduced to cysteine, the rate-limiting building block of glutathione. Malfunctioning of system xc- can thus cause oxidative stress as well as excitotoxicity, important phenomenons in the pathogenesis of Parkinson's disease, epilepsy, multiple sclerosis and many other neurological disorders. However, deletion of xCT (xCT-/- mice) did not affect striatal or hippocampal glutathione levels and no signs of increased oxidative stress were seen in xCT-/- mice. Interestingly, extracellular hippocampal and striatal glutamate levels were decreased by >60% in xCT-/- mice compared to controls. In addition, intrahippocampal perfusion with system xc- inhibitors lowered extracellular glutamate whereas the system xc- activator N-acetylcysteine elevated extracellular glutamate in rat hippocampus, suggesting that system xc- might be an interesting target for pathologies associated with excessive extracellular glutamate release. Indeed, we observed increased expression levels of xCT, the specific subunit of system xc-, in brain samples of rodent models for several neurological disorders as well as patients. To investigate the relevance of this altered expression of xCT, we used xCT-/- mice to study in vivo the effect of system xc- deficiency on the behavioral and/or neurochemical outcome in models for Parkinson's disease, limbic seizures, epilepsy and multiple sclerosis. xCT deletion resulted in protection of the mice in models for Parkinson's disease, limbic seizures and epilepsy. Loss of xCT did not affect the susceptibility of mice in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis. The current data sustain that system xc- is an important source of hippocampal and striatal extracellular glutamate that might become activated in pathological conditions and as such cause accumulation of extracellular glutamate to toxic levels. Inhibition of system xc- might thus represent an innovative strategy for the future development of drugs for the treatment of neurological disorders that are characterized by dysregulated glutamatergic neurotransmission.

AB - System xc- or the cystine/glutamate antiporter imports one cystine in exchange for one glutamate molecule. Cystine is intracellularly reduced to cysteine, the rate-limiting building block of glutathione. Malfunctioning of system xc- can thus cause oxidative stress as well as excitotoxicity, important phenomenons in the pathogenesis of Parkinson's disease, epilepsy, multiple sclerosis and many other neurological disorders. However, deletion of xCT (xCT-/- mice) did not affect striatal or hippocampal glutathione levels and no signs of increased oxidative stress were seen in xCT-/- mice. Interestingly, extracellular hippocampal and striatal glutamate levels were decreased by >60% in xCT-/- mice compared to controls. In addition, intrahippocampal perfusion with system xc- inhibitors lowered extracellular glutamate whereas the system xc- activator N-acetylcysteine elevated extracellular glutamate in rat hippocampus, suggesting that system xc- might be an interesting target for pathologies associated with excessive extracellular glutamate release. Indeed, we observed increased expression levels of xCT, the specific subunit of system xc-, in brain samples of rodent models for several neurological disorders as well as patients. To investigate the relevance of this altered expression of xCT, we used xCT-/- mice to study in vivo the effect of system xc- deficiency on the behavioral and/or neurochemical outcome in models for Parkinson's disease, limbic seizures, epilepsy and multiple sclerosis. xCT deletion resulted in protection of the mice in models for Parkinson's disease, limbic seizures and epilepsy. Loss of xCT did not affect the susceptibility of mice in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis. The current data sustain that system xc- is an important source of hippocampal and striatal extracellular glutamate that might become activated in pathological conditions and as such cause accumulation of extracellular glutamate to toxic levels. Inhibition of system xc- might thus represent an innovative strategy for the future development of drugs for the treatment of neurological disorders that are characterized by dysregulated glutamatergic neurotransmission.

KW - system xc-

KW - xCT

KW - glutamate

M3 - Meeting abstract (Book)

BT - Conferences on amino-acidergic transmission: Glutamate/GABA and Neuro-Glia-Vascular Interplay in Norm and Pathology, 21-24 May 2014, Krakow, Poland

ER -

ID: 2510143