Mitochondrial activity in human glioma cells and your relationship with the Warburg effect

• Grant number: 13/17837-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2013
• Effective date (End): December 31, 2014
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Roger Frigério Castilho
• Grantee: Erika Rodrigues da Silva
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 11/50400-0 - Mitochondrial energy metabolism, redox state and functionality in cell death and cardiometabolic and neurodegenerative disorders, AP.TEM

Abstract

The object of the present project is to evaluate the mitochondrial bioenergetics in human glioma cells (T98G and U87MG), the results will be correlated with the predominant glycolytic metabolism of these cells, even when incubated in the presence of molecular oxygen (Warburg effect). The objectives are I) To evaluate the occurrence of the Warburg effect under our experimental conditions; II) To determine the coupling between the oxygen consumption and ATP synthesis in mitochondria from the glioma cells; III) To correlate the capacity for oxidative phosphorylation and respiratory chain activity in the glioma cells; IV) To evaluate the availability of Krebs cycle substrates during glioma cell growth; v) To determine the p50 for O2 for the glioma cells T98G and U87MG; vi) To evaluate the impact of the oxidative phosphorylation inhibition on the cytotoxicity of the chemotherapeutic agent temozolomide for T98G and U87MG cells, and VII) To verify if fresh tissue obtained from human gliomas (grade IV) display similar characteristics regarding the oxidative metabolism when compared with the cell lines. The present Project may help to elucidate the relationship between the mitochondrial activity in tumor cells and the occurrence of the Warburg effect. The treatment of glioblastoma multiforme (grade IV) is still ineffective in most cases and this tumor presents rapid progress. Understand the mitochondrial bioenergetics of these cells and their relationship with the Warburg effect may contribute to the proposition of more effective therapeutic approaches. (AU)