论文部分内容阅读
Objective Silent information regulator 1 (SIRT1), an NAD+-dependent deacetylase, is involved in the regulation of gene transcription, energy metabolism, and cell aging.Recent studies have showed that SIRT1 possesses neuroprotective effects, however, it is unknown whether it protects neurons from NMDA-mediated neurotoxicity.Here we observed the role of SIRT1 in the cellular model of NMDA-mediated neurotoxicity (100 μmol/L, 2 h) using resveratrol as SIRT1 activator.Methods Cell viability was measured by WST-8 assay, LDH levels assay and Calcein-AM staining.The levels of SIRT1 protein, P53 protein, and acetylation of P53 were identified by Western-blot.SIRT1 mRNA levels was detected by RT-PCR.Results (1) Treatment of cultured cortical cell with resveratrol elicited dose-dependent inhibitory effects on NMDA-induced excitotoxicity.Resveratrol (25 tmol/L) pre-ineubated for 12 h inhibited NMDA-induced decrease of cell viability by 26.07% (P < 0.05), attenuated NMDA-induced leakage of LDH by 29.90% (P < 0.05) and suppressed NMDA-induced decrease of living cells by 25.19% (P < 0.05).(2) Both Western-blot and RT-PCR analysis showed that resvertrol could not inhibit NMDA-induced decrease of SIRT1 protein and mRNA levels, however, resvertrol could suppress NMDA-induced increase of the acetylation of P53, a downstream target of SIRT1 activation, which means under excitotoxic conditions, resvertrol increased activity of SIRT1 to protect neurons, in part by hindering the acetylation of P53.Conclusion The present study demonstrated the neuroprotective roles of SIRT1 in NMDA-induced excitotoxicity in cortical neurons, therefore, SIRT1 could be a novel target for preventing and treating neurodegeneration.