Aysenur Akkulak1, Düriye Nur Dağdelen1, Abdullah Yalçın1, Esin Oktay2, Gülden Diniz3, Dudu Solakoğlu Kahraman4, Mehmet Şenoğlu5, Gizem Donmez Yalcin6. 1. Faculty of Medicine, Department of Medical Biology, Aydin Adnan Menderes University, Merkez Kampus, Aydin, Turkey. 2. Faculty of Medicine, Department of Medical Oncology, Aydin Adnan Menderes University, Aydin, Turkey. 3. Department of Pathology, Izmir Democracy University, Izmir, Turkey. 4. Department of Pathology, Tepecik Training and Research Hospital, Izmir, Turkey. 5. Department of Brain Surgery, KTO Karatay University, Medicana International Hospital Izmir, Konya, Turkey. 6. Faculty of Medicine, Department of Medical Biology, Aydin Adnan Menderes University, Merkez Kampus, Aydin, Turkey. gizem.yalcin@adu.edu.tr.
Abstract
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.
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.