2011 YÜksek lisans tez özetleri

The Role of Nerve Growth Factor and Histone Deacetylase Inhibitors in C6 Glioma Cells

Removal of acetyl moieties from histones and other proteins is used widely as a therapeutic aim in cancer and neurodegenerative diseases. Histone deacetylase inhibitors stimulate the hyperacetylation in chromatin, which causes activation of some genes and it also stimulates the terminal cell differentiation and/or apoptosis. Valproic acid (VPA) is an agent whose powerful antiepileptic, antineoplastic and neuroprotective features are known and it can change the expression of several targets including neurotrophines in central nervous system. Trichostatin A (TSA) inhibites cellular cycle in the beginning of growth period in eucaryotic cells and it can change gene expression by inhibiting removal of acetyl groups from histones. These histone deacetylase inhibitors have antitumour activity and antiinflammatory properties. It is known that rat C6 glioma cells express nerve growth factor (NGF) receptors both in vitro and in vivo, and they also cause differentiation of these cells, leading to inhibition of their proliferation.

This study is designed to determine the effects of two histone deacetylase inhibitors in combined manner on especially apoptosis and cellular proliferation mechanism in C6 glioma cells and relationship to the administration of NGF. Therefore, it was aimed to investigate the inexplicable cell death mechanism of C6 glioma cells at molecular level.

By considering all these findings, VPA and TSA administered different doses and periods (individually and in combined manner) and apoptotic cellular index and cellular proliferation index calculated. In addition, the effect of these histone deacetylase inhibitors in vitro on especially apotosis and cellular proliferation mechanisms in C6 glioma cells, the relationship to the administration of NGF are determined. In this study, caspase-3 activity, P75^NTR and TrkA determined with immunocytochemical manner whereas the NGF levels, cell proliferation and cell death determined with colorimetric (ELISA) manner.

As a result, we report that VPA, TSA and NGF individually and combined manner inhibit the cell proliferation of C6 glioma cells and trigger apoptosis. By considering these findings, we suggest that VPA, TSA and NGF combination may be new therapeutic agents in the therapy of neurodegenerative diseases and glial derivative brain cancer.

  

ÇETİN İdil

Danışman : Y.Doç.Dr. Mehmet TOPÇUL

Anabilim Dalı : Biyoloji

Programı : Genel Biyoloji

Mezuniyet Yılı : 2011

Tez Savunma Jürisi : Y.Doç.Dr. Mehmet TOPÇUL

Prof. Dr.Tulay ENGİZEK

Prof.Dr. Tuncay ORTA

Doç. Dr. Gül ÖZCAN ARICAN

Doç.Dr. Ali KARAGÖZ