关键词: 表观遗传修饰, DNA双加氧酶TET2, 氧化应激, 神经保护

Abstract:

Objective To detect the expression of DNA dioxygenase Ten-Eleven Translocation 2 (TET2) in the brain tissue of Alzheimer's disease(AD) animal models,and to explore the protective effect of TET2 protein on the neurons under oxidative stress. Methods The C57BL/6 mice were divided into adult group,old age group and AD group,which were 8 weeks,8 months normal mice and 8 months Alzheimer's transgenic mice, respectively.The TET2 mRNA levels in the cerebral cortex,hippocampus and cerebellum tissue of the mice in three groups were examined using Real-time quantitative PCR.The hippocampal neuron cell lines HT22 of mice were randomly divided into normal group,control group,lentivirus control group (N.C.shRNA) and lentivirus-mediated TET2 interference groups (TET2 shRNA-1 and TET2 shRNA-2).After 72 h of lentivirus infection,the HT22 cells in control group,N.C.shRNA group and two TET2 shRNA groups were given 50 μmol·L^-1 hydrogen peroxide (H₂O₂) and 2.5 mmol·L^-1 L-homocysteic acid (L-HCA) for 4 h to establish the extracellular and intracellular oxidative stress models,then the viabilities of the cells in various groups were determined with MTT method. Results With the increase of age,the TET2 mRNA in the cortex,hippocampus and cerebellum were increased markedly. Compared with old age group,the TET2 mRNA expression levels in the cortex,hippocampus and cerebellum tissue of the mice in AD group were significantly decreased (P<0.05 or P<0.01). The survival rate of the neurons in TET2 shRNA-2 group was significantly lower than that in N.C shRNA group in H₂O₂ and L-HCA mediated oxidative stress models (P<0.01). Conclusion The expression level of TET2 in brain tissue of the AD mice is notably reduced,and the down-regulation of TET2 causes the neurons to be more susceptible to oxidative damage,which implicating that TET2 maybe protect the neurons against oxidative stress.

Key words: epigenetic modification, DNA dioxygenase TET2, oxidative stress, neuroprotection