|
|
Protective effects of 5-Aza-2’-deoxycytidine on neurotoxicity of hippocampal neurons induced by benzo[a]pyrene |
WEI Zhichao1 FENG Jingyu2 NIE Jisheng1 WEI Jianhong2#br# |
1.School of Public Health, Shanxi Medical University, Shanxi Province, Taiyuan 030000, China;
2.Fenyang College of Shanxi Medical University, Shanxi Province, Fenyang 032200, China
|
|
|
Abstract Objective To probe the protective effects of 5-Aza-2’-deoxycytidine (5-Aza-cdR) on the neurotoxicity of benzo[a] pyrene(B[a]P) to hippocampal neurons. Methods The hippocampal neurons were cultured until the 5th day. The cells were observed and identified. The experiment was divided into control group, B[a]P group(20 μmol/L, B[a]P), and B[a]P+5-Aza-cdR group (20 μmol/L B[a]P+10 μmol/L 5-Aza-cdR). Cell morphology was observed. Cell viability, DNA methyltransferase protein, and gene expression were detected. Total methylation level and apoptosis were measured. Results Compared with the control group, the B[a]P group decreased the viability of hippocampal neurons(P<0.05). The apoptosis rate increased (P<0.05). The expression level of DNMT3A, DNMT3B gene and DNMT1、DNMT3A protein increased (P<0.05). The total methylation level increased (P<0.05). Compared with the B[a]P group, the B[a]P+5-Aza-cdR group increased hippocampal neuronal viability (P<0.05), and the apoptosis rate decreased (P<0.01) and visibly decreased DNMTs gene and protein expression levels (P<0.05). The methylation level was obviously decreased (P<0.01). Conclusion 5-Aza-cdR has a protective effect on B[a] P-induced hippocampal neuron injury.
|
|
|
|
|
[1] 王冲.表观遗传修饰对突触可塑性的调控作用研究进展[J].动物医学进展,2018,39(9):83-86.
[2] Zhang L,Lu Q,Chang C. Epigenetics in Health and Disease [J]. Adv Exp Med Biol,2020,1253:3-55.
[3] 于明懂,于泳浩,李佩,等.DNA甲基化在神经发育及中枢神经系统相关疾病中的作用研究进展[J].山东医药,2021,61(16):92-96.
[4] 钟焱,徐慧,彭凤兰.DNA甲基化在基因表达调控中的意义及研究进展[J].中国医药导报,2019,16(14):33-36.
[5] Nugent BM,Wright CL,Shetty AC,et al. Brain feminization requires active repression of masculinization via DNA methylation [J]. Nat Neurosci,2015,18(5):690-697.
[6] 刘丽.苯并芘对环境的影响及其检测方法研究进展[J].清洗世界,2020,36(3):31-32.
[7] 张楠,张英英,王鹤霏,等.氯化锂对苯并[a]芘暴露致大鼠胚胎海马神经元损伤的改善作用[J].环境与职业医学,2021,38(5):482-488.
[8] 阎智伟,段蕾,聂继盛.苯并[a]芘亚慢性染毒致大鼠学习记忆功能损伤及Tau蛋白磷酸化改变[J].中国职业医学,2014,41(2):132-136.
[9] Liu D,Zhao Y,Qi Y,et al. Benzo(a)pyrene exposure induced neuronal loss,plaque deposition,and cognitive decline in APP/PS1 mice [J]. J Neuroinflammation,2020,17(1):258.
[10] Fish TJ,Benninghoff AD. DNA methylation in lung tissues of mouse offspring exposed in utero to polycyclic aromatic hydrocarbons [J]. Food Chem Toxicol,2017,109(Pt 1):703-713.
[11] Zhang CM,Sun ZX,Wang ZL,et al. Abnormal methylation of spermatozoa induced by benzo(a)pyrene in rats [J]. Hum Exp Toxicol,2019,38(7):846-856.
[12] Zhao L,Zhang S,An X,et al. Toxicological effects of benzo[a]pyrene on DNA methylation of whole genome in ICR mice [J]. Cell Mol Biol (Noisy-le-grand),2015,61(5):115-119.
[13] 姜树原,王强,张晓璐,等.5-Aza-CdR对HT22小鼠海马神经元细胞中NR2B磷酸化的影响[J].包头医学院学报,2020,36(5):40-42.
[14] Kong M,Ba M,Liang H,et al. 5’-Aza-dC sensitizes paraquat toxic effects on PC12 cell [J]. Neurosci Lett,2012,524(1):35-39.
[15] Aktay G,Emre MH,Polat A. Influence of dihydropyridine calcium antagonist nitrendipine on benzo(a)pyrene-induced oxidative stress [J]. Arch Pharm Res,2011,34(7):1171-1175.
[16] 冀晓莹,高美丽.苯并(a)芘神经毒性研究进展[J].生态毒理学报,2016,11(3):47-52.
[17] 韩隽韬,张宇,聂继盛.孕期苯并[a]芘暴露对子代大鼠大脑皮质芳香烃受体表达及其与芳香烃受体核转运蛋白2相互作用的影响[J].环境与职业医学,2021,38(4):332-335.
[18] Bukowska B,Sicinska P. Influence of Benzo(a)pyrene on Different Epigenetic Processes [J]. Int J Mol Sci,2021,22(24):13453.
[19] He CC,Wang ZY,Tian K,et al. DNA methylation mechanism of intracellular zinc deficiency-induced injury in primary hippocampal neurons in the rat brain [J]. Nutr Neurosci,2018,21(7):478-486.
[20] 曹晶晶,郝忠锁,刘爱香,等.DNA甲基转移酶在苯并[a]芘致小鼠空间学习记忆功能障碍中的改变[J].环境卫生学杂志,2018,8(1):1-6.
[21] Zhang Z,Yang J,Liu X,et al. Effects of 5-Aza-2’-deoxycytidine on expression of PP1γamma in learning and memory [J]. Biomed Pharmacother,2016,84:277-283.
[22] 张柱霞,孙明英,杨洁,等.5-Aza-CdR和低氧对小鼠海马中蛋白磷酸酶-1γ表达及对学习记忆的影响[J].动物医学进展,2015,36(9):59-63.
[23] 田小莉,杨洁,杨静,等.5-氮杂-2’-脱氧胞苷对小鼠海马神经元细胞系HT22细胞DNA甲基转移酶表达和细胞周期的影响[J].解剖学杂志,2018,41(4):404-408.
[24] 张世纪,付翁,贾小娥,等.5-Aza-cdR通过DNA甲基化调节BDNF参与学习记忆的机制[J].包头医学院学报,2022,38(1):21-25.
[25] Fan X Y,Shi G,Zhao P. Neonatal Sevoflurane Exposure Impairs Learning and Memory by the Hypermethylation of Hippocampal Synaptic Genes [J]. Mol Neurobiol,2021,58(3):895-904. |
|
|
|