The expression of glutamate metabolism modulators in the intracranial tumors and glioblastoma cell line

Background The accumulation of excess glutamate in the synapse leads to excitotoxicity, which is the underlying reason of neuronal death in intracranial tumors. Methods and results We identified the expression levels of glutamate dehydrogenase, glutamine synthetase and sirtuin 4 in U87 cell line and various intracranial tumors. mRNA expressions of glutamate dehydrogenase (GDH), glutamine synthetase (GS) and sirtuin 4 (SIRT4) were analyzed in various intracranial tumors using qPCR. GDH, GS and SIRT4 protein expressions were analyzed in glioblastoma (U87) and glial (IHA-immortalized human astrocytes) cell lines via western blotting. The protein expressions of SIRT4 and GS were shown to be elevated and GDH protein expression was reduced in U87 cells in comparison to IHA cells. All types of intracranial tumors displayed lower GS mRNA expressions compared to controls. SIRT4 mRNA expressions were also shown to be lower in all the tumors and grades, although not significantly. GDH mRNA expression was found to be similar in all groups. Conclusion The molecular mechanisms of glutamate metabolism and excitotoxicity should be discovered to develop therapies against intracranial tumors.

Automated summary

The study found that intracranial tumors exhibit excitotoxicity caused by glutamate metabolism disorders, analyzed the expression levels of glutamate dehydrogenase, glutamine synthetase and sirtuin 4 in intracranial tumor cells, and found that SIRT4 and GS are expressed at higher levels in U87 cells while GDH is expressed at lower levels, suggesting that understanding the mechanisms of glutamate metabolism and excitotoxicity in intracranial tumors may help in the development of therapies.