Excitatory amino acid transporter 3 and the glutamate/cystine antiporter system Xc- cooperatively protect neuronal HT22 cells from oxidative glutamate toxicity

Oxidative stress plays a role in many neurological diseases such as Alzheimer's and Parkinson's disease, or stroke. Oxidative glutamate toxicity in the mouse hippocampal cell line HT22 serves as a model system for neuronal death in response to oxidative stress, in which excess extracellular glutamate inhibits the import of cystine via the glutamate/cystine antiporter system Xc-. Cystine is a crucial constituent for the synthesis of the antioxidant glutathione (GSH), and thus induces intracellular GSH depletion, followed by a rise in reactive oxygen species and programmed cell death. To characterize pathways of r…