Quercetin prevents protein nitration and glycolytic block of proliferation in hydrogen peroxide insulted cultured neuronal precursor cells (NPCs): Implications on CNS regeneration.

摘要: Survival along with optimal proliferation of neuronal precursors determines the outcomes endogenous cellular repair in CNS. Cellular-oxidation based cell death has been described several neurodegenerative disorders. Therefore, this study was aimed at identification potent targets oxidative damage to and its effective prevention by a natural flavonoid, Quercetin. Neuronal precursor cells (NPCs), Nestin+ GFAP (Glial fibrillary acidic protein)+ were isolated cultured from adult rat SVZ (subventricular zone). These challenged single dose H2O2 (50μM) and/or pre-treated different concentrations severely limited viability expansion neurospheres. studies revealed reduction glutathione dependent redox buffering depletion enzymatic antioxidants that might potentiate nitrite (NO2(-)) superoxide anion (O2(-)) mediated peroxynitrite (ONOO(-)) formation irreversible protein nitration. We identified depleted PK-M2 (M2 isoform pyruvate kinase) activity apoptosis NPCs genomic DNA fragmentation elevated PARP (poly ADP ribose polymerase) increased Caspase initiated depolarised mitochondrial membranes. However, pre-treatment Quercetin dose-response manner prevented these changes restored neurospheres preferably neutralizing conditions thereby reducing formation, nitration depletion. Our results unravel potential interactions environment respiration survival activation offer promise shown flavonoid protective strategy for brain.