Compromised Glutamate Transport in Human Glioma Cells: Reduction–Mislocalization of Sodium-Dependent Glutamate Transporters and Enhanced Activity of Cystine–Glutamate Exchange

摘要: Elevated levels of extracellular glutamate ([Glu] o ) can induce seizures and cause excitotoxic neuronal cell death. This is normally prevented by astrocytic uptake. Neoplastic transformation human astrocytes causes malignant gliomas, which are often associated with necrosis. Here, we show that Na + -dependent uptake in glioma lines derived from tumors (STTG-1, D-54MG, D-65MG, U-373MG, U-251MG, U-138MG, CH-235MG) up to 100-fold lower than astrocytes. Immunohistochemistry subcellular fractionation very low expression the transporter GLT-1 but normal another glial transporter, GLAST. However, cells, essentially all GLAST protein was found nuclei rather plasma membrane. Similarly, brain tissues glioblastoma patients also display reduction mislocalization In lines, over 50% transport -independent mediated a cystine–glutamate exchanger (system x c − ). Extracellularl-cystine dose-dependently induced release cells. Glutamate enhanced glutamine inhibited ( S )-4-carboxyphenylglycine, blocked exchange. These data suggest unusual cells caused reduction–mislocalization transporters conjunction upregulation The resulting may contribute tumor-associated necrosis possibly peritumoral tissue.