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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2011

Open Access 01-12-2011 | Research

Increased expression of cystine/glutamate antiporter in multiple sclerosis

Authors: Olatz Pampliega, María Domercq, Federico N Soria, Pablo Villoslada, Alfredo Rodríguez-Antigüedad, Carlos Matute

Published in: Journal of Neuroinflammation | Issue 1/2011

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Abstract

Background

Glutamate excitotoxicity contributes to oligodendrocyte and tissue damage in multiple sclerosis (MS). Intriguingly, glutamate level in plasma and cerebrospinal fluid of MS patients is elevated, a feature which may be related to the pathophysiology of this disease. In addition to glutamate transporters, levels of extracellular glutamate are controlled by cystine/glutamate antiporter xc -, an exchanger that provides intracellular cystine for production of glutathione, the major cellular antioxidant. The objective of this study was to analyze the role of the system xc - in glutamate homeostasis alterations in MS pathology.

Methods

Primary cultures of human monocytes and the cell line U-937 were used to investigate the mechanism of glutamate release. Expression of cystine glutamate exchanger (xCT) was quantified by quantitative PCR, Western blot, flow cytometry and immunohistochemistry in monocytes in vitro, in animals with experimental autoimmune encephalomyelitis (EAE), the animal model of MS, and in samples of MS patients.

Results and discussion

We show here that human activated monocytes release glutamate through cystine/glutamate antiporter xc - and that the expression of the catalytic subunit xCT is upregulated as a consequence of monocyte activation. In addition, xCT expression is also increased in EAE and in the disease proper. In the later, high expression of xCT occurs both in the central nervous system (CNS) and in peripheral blood cells. In particular, cells from monocyte-macrophage-microglia lineage have higher xCT expression in MS and in EAE, indicating that immune activation upregulates xCT levels, which may result in higher glutamate release and contribution to excitotoxic damage to oligodendrocytes.

Conclusions

Together, these results reveal that increased expression of the cystine/glutamate antiporter system xc - in MS provides a link between inflammation and excitotoxicity in demyelinating diseases.
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Metadata
Title
Increased expression of cystine/glutamate antiporter in multiple sclerosis
Authors
Olatz Pampliega
María Domercq
Federico N Soria
Pablo Villoslada
Alfredo Rodríguez-Antigüedad
Carlos Matute
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2011
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-8-63

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