The cystine/glutamate antiporter: when too much of a good thing goes bad
Kathryn J. Reissner
Kathryn J. Reissner
Published July 18, 2014
Citation Information: J Clin Invest. 2014;124(8):3279-3281. https://doi.org/10.1172/JCI76627.
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Commentary

The cystine/glutamate antiporter: when too much of a good thing goes bad

Abstract

Glutamate excitotoxicity represents a major cellular component of ischemic brain injury. In this issue of the JCI, Soria and colleagues reveal that the cystine/glutamate exchanger is an important source of excitotoxic glutamate in response to ischemia induced by oxygen and glucose deprivation. As the exchanger is a primary determinant of both extracellular glutamate and intracellular glutathione, the findings from this study not only provide important insight into the mechanisms of brain ischemia but also demonstrate the complexity of the yin and yang of glutamate homeostasis and cellular redox balance.

Authors

Kathryn J. Reissner

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Figure 1

Systematic analysis of the source of excitotoxic glutamate during ischemic brain injury.

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Systematic analysis of the source of excitotoxic glutamate during ischem...
Excitotoxic glutamate (brown circles) released during oxygen and glucose deprivation in culture could potentially derive from reverse transport from high-affinity glutamate transporters (i, yellow), vesicular glutamate release (ii), or the cystine/glutamate exchanger (iii, green). Exchange of glutamate release for cystine uptake by the exchanger is indicated with bidirectional arrows. Soria and colleagues have demonstrated that glutamate released from the cystine/glutamate exchanger activates extrasynaptic NR2B–containing receptors (iii, purple), as opposed to synaptic NR2A–containing receptors (blue).