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Fgf-2 Induces Neuronal Death Through Upregulation Of System Xc-, Xiaoqian Liu, Rebecca Albano, Doug Lobner
Fgf-2 Induces Neuronal Death Through Upregulation Of System Xc-, Xiaoqian Liu, Rebecca Albano, Doug Lobner
Biomedical Sciences Faculty Research and Publications
The cystine/glutamate antiporter (system xc-) transports cystine into cell in exchange for glutamate. Fibroblast growth factor-2 (FGF-2) upregulates system xc- selectively on astrocytes, which leads to increased cystine uptake, the substrate for glutathione production, and increased glutamate release. While increased intracellular glutathione can limit oxidative stress, the increased glutamate release can potentially lead to excitotoxicity to neurons. To test this hypothesis, mixed neuronal and glial cortical cultures were treated with FGF-2. Treatment with FGF-2 for 48 h caused a significant neuronal death in these cultures. Cell death was not observed in neuronal-enriched cultures, or astrocyte-enriched …