Lithium effect on glutamate induced damage in glioblastoma cells

Jakopec, Sanjica and Karlović, Dalibor and Dubravčić, Klara and Batinić, Drago and Sorić, Jasna and Brozović, Anamaria and Buljan, Danijel and Osmak, Maja (2008) Lithium effect on glutamate induced damage in glioblastoma cells. Collegium Antropologicum, 32 (S. 1). pp. 87-91. ISSN 0350-6134

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Abstract

Lithium, besides mood stabilization, might be involved in neuroprotection. Previously we have found that the treatment with lithium increased the levels of p21(WAF/Cip1 and survivin in human glioblastoma A1235 cells. The aim of the present study was to examine the cytotoxic effect of glutamate on these cells, and to determine whether lithium can protect A1235 cells against toxic effects of glutamate. Cytotoxicity of glutamate was examined by spectrophotometric MTT assay, while the expression of apoptosis related genes was examined by Western blot method. Glutamate was excessively cytotoxic for A1235 cells only in concentrations higher than 100 mM. It did not induce apoptosis, but rather suppressed survivin expression and increased the level of p21(WAf/Cip1). Pretreatment with lithium (2 mM) partially reverted change in survivin expression induced by glutamate, suggesting that lithium may have beneficial effect on glutamate induced cell damage in glioblastoma cells.

Abstract in Croatian

Osim stabilizacije raspoloženja, litij može imati i neuroprotektivni učinak. Prije smo pokazali da tretiranje ljudskih stanica glioblastoma A1235 litijem povećava ekspresiju proteina p21WAF/Cip1 i survivina. Cilj ovog istraživanja bio je ispitati citotoksični učinak glutamata na istim stanicama, i odrediti da li litij može zaštititi A1235 stanice od toksičnog učinka glutamata. Citotoksičnost glutamata određivana je spektrofotometrijskom MTT metodom, a ekspresija apoptotskih gena Western blot metodom. Glutamat je bio izrazito toksičan za A1235 stanice samo u koncentracijama višim od 100 mM. Nije izazivao apoptozu, već smanjivao ekspresiju survivina i povećavao ekspresiju p21WAF/Cip1. Predtretman sa litijem djelomično je dokinuo promjene u ekspresiji survivina inducirane glutamatom. U zaključku, visoke koncentracije glutamata toksične su za stanice glioblastoma. Kod tih koncentracija predtretman stanica sa litijem (2 mM) dokida supresiju survivina izazvanu glutamatom, što upućuje na zaključak da bi litij mogao imati pozitivan učinak na glutamatom izazvana oštećenja u stanicama glioblastoma.

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