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- Title
Expression and Developmental Regulation of the Cystine/Glutamate Exchanger (x <sub>c</sub><sup>â</sup> ) in the Rat.
- Authors
Vincenzo La Bella; Francesca Valentino; Tommaso Piccoli; Federico Piccoli
- Abstract
Abstract  The cystine/glutamate exchanger (antiporter xcâ) is a membrane transporter involved in the uptake of cystine, the rate-limiting amino acid in the synthesis of glutathione. Recent studies suggest that the antiporter plays a role in the slow oxidative excitotoxity and in the pathological effects of β-N-oxalylamino-l-alanine, the molecule responsible for neurolathyrism, a neurotoxic upper motor neuron disease. The mouse cystine/glutamate exchanger has been cloned and showed to be composed of two distinct proteins, one of which being a novel protein, named xCT, of 502 amino acids and 12 putative trans-membrane domains. We have generated and purified a polyclonal antibody to mouse xCT and studied its expression in rat brain and in different cultured cells (astrocytes, fibroblasts and neurons) using Western blot and immunocytochemical techniques. Expression of xCT was also studied in rat brain and muscle at different developmental stages. Parallel experiments were carried out with antibodies to the heavy chain of 4F2 surface antigen, the non-specific subunit of the antiporter xcâ. xCT antibody detected in all cell and tissue extracts a specific band of about 40 kDa. Subcellular fractionation demonstrated that xCT is concentrated mainly in the microsomal-mitochondrial fraction, in accord with its structure as transmembrane protein. Immunocytochemical analysis showed a strong staining in all cells examined, included neurons. Furthermore, both xCT and the heavy chain of 4F2 surface antigen increased in the brain during development, reaching the highest expression in adulthood. The study of the expression and developmental profile of xCT represents a first step towards a better characterization of its biochemical properties and function, which in turn may help to understand the relative contribution of the xcâ antiporter in the pathogenesis of certain neurodegenerative diseases.
- Subjects
NEURONS; AMINO acids; NERVOUS system; GLUTATHIONE
- Publication
Neurochemical Research, 2007, Vol 32, Issue 6, p1081
- ISSN
0364-3190
- Publication type
Article
- DOI
10.1007/s11064-006-9277-6