Distribution of the Cystine/Glutamate Antiporter System x^-_c in the Brain, Kidney, and Duodenum

Joseph Burdo ¹, Richard Dargusch ¹ and David Schubert ^1*

¹ The Salk Institute for Biological Studies Cellular Neurobiology Laboratory, La Jolla, California

^* To whom correspondence should be addressed. E-mail: Schubert{at}salk.edu.

Submitted on September 16, 2005
Accepted on 2 December 2005

	Abstract

System x^-_c, one of the main transporters responsible for CNS cystine transport, is comprised of two subunits, xCT and 4F2hc. The transport of cystine into cells is rate limiting for glutathione synthesis, the major antioxidant and redox cofactor in the brain. Alterations in glutathione status are prevalent in numerous neurodegenerative diseases, emphasizing the importance of proper cystine homeostasis. However, the distribution of xCT and 4F2hc within the brain and other areas has not been described. Using specific antibodies, both xCT and 4F2hc were found to localize predominantly to neurons in the mouse and human brain, but some glial cells were labeled as well. Border areas between the brain proper and periphery including the vascular endothelial cells, ependymal cells, choroid plexus and leptomeninges were also highly positive for the system x^-_c components. xCT and 4F2hc are also present at the brush border membranes in the kidney and duodenum. These results indicate that system x^-_c is likely to play a role in cellular health throughout many areas of the brain as well as other organs by maintaining intracellular cystine levels, thereby resulting in low levels of oxidative stress.

Key Words: xCT, system x^-_c, 4F2hc, glutathione, cystine, brain, duodenum, kidney, cystinuria

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