Functional Modulation of Mitochondria by Eicosapentaenoic Acid Provides Protection against Ceramide Toxicity to C6 Glioma Cells

Mitochondrial dysfunction and associated apoptosis have been reported in the pathogenesis of neuron degeneration. The effects of eicosapentaenoic acid (EPA) and arachidonic acid (AA) on the mitochondrial membrane potential, mitochondrial biogenesis, and mitochondrial function of rat C6 glioma cells were determined in this study. Increased cytochrome c release and activated caspase-3 expression were determined in cells treated with >20 μM C2 ceramide. There were significant repressive effects on ceramide-induced cell death with 25−100 μM EPA and 25 μM AA pretreatment. However, significantly increased membrane potentials were detected in cells pretreated with 25 and 50 μM EPA compared to ceramide-treated cells, but not in AA pretreatment groups. In cells pretreated with EPA, ATP production loss was prevented from ceramide-induced mitochondrial dysfunction. In mitochondrial biogenesis related assay, both EPA and AA enhanced peroxisome proliferator-activated receptor γ-coactivator-1α (PGC-1α) and mitochondria...