TY - JOUR
T1 - A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium
AU - Di Angelantonio, S.
AU - Murana, E.
AU - Cocco, S.
AU - Scala, F.
AU - Bertollini, C.
AU - Molinari, M. G.
AU - Lauro, C.
AU - Bregestovski, P.
AU - Limatola, C.
AU - Ragozzino, D.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of ?-aminobutyric acid (GABA)-evoked currents (EGABA). EGABA depolarizing shift is due to zinc-dependent reduction of neuronal KCC2 activity and requires glutamate release from glioma cells. Consistently, intracellular zinc loading rapidly depolarizes EGABA in mouse hippocampal neurons, through the Src/Trk pathway and this effect is promptly reverted upon zinc chelation. This study provides a possible molecular mechanism linking glioma invasion to excitation/inhibition imbalance and epileptic seizures, through the zinc-mediated disruption of neuronal chloride homeostasis.
AB - Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of ?-aminobutyric acid (GABA)-evoked currents (EGABA). EGABA depolarizing shift is due to zinc-dependent reduction of neuronal KCC2 activity and requires glutamate release from glioma cells. Consistently, intracellular zinc loading rapidly depolarizes EGABA in mouse hippocampal neurons, through the Src/Trk pathway and this effect is promptly reverted upon zinc chelation. This study provides a possible molecular mechanism linking glioma invasion to excitation/inhibition imbalance and epileptic seizures, through the zinc-mediated disruption of neuronal chloride homeostasis.
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U2 - 10.1038/cddis.2014.437
DO - 10.1038/cddis.2014.437
M3 - Article
C2 - 25356870
AN - SCOPUS:84928010701
VL - 5
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 10
M1 - e1501
ER -