The metabolic enhancer piracetam attenuates the mitochondrion-specific endonuclease-G translocation and oxidative DNA fragmentation

Abstract

The present study was performed to investigate the involvement of mitochondrion – specific endonuclease G in piracetam (P) induced protective mechanisms. Studies have showed the antiapoptotic effect of piracetam but still there are some unfold enigma for the mechanism of action of piracetam. To assess the involvement of endonuclease G in piracetam induced protective effects, the astrocyte glial cells were treated with Lipopolysaccharide (LPS) / LPS+P. LPS treatment caused significantly decreased viability, mitochondrial activity, oxidative stress, chromatin condensation and DNA fragmentation which were attenuated with piracetam co-treatment. Piracetam co-treated astrocytes showed its significant time dependent absorption as observed with high performance liquid chromatography data. Piracetam per se treated astrocytes showed the enhanced mitochondrial membrane potential (MMP) in comparison to control astrocytes. However, in LPS treated cells no significant alteration in MMP was observed in comparison to control cells. Protein and mRNA levels of terminal executor of caspase mediated pathway, caspase-3 did not alter significantly in LPS or LPS+P treated astrocytes whereas endonuclease G was significantly translocated to nucleus in LPS treated astrocytes. Piracetam co-treatment attenuated the LPS induced endonuclease G translocation. In conclusion study indicates that LPS treatment to astrocytes caused decreased viability, oxidative stress, mitochondrial dysfunction, chromatin condensation, DNA damage and translocation of endonuclease G to nucleus which was inhibited with piracetam co-treatment and confirming the mitochondrion-specific endonuclease G as one of the factor involved in piracetam induced protective mechanisms.