RG108对HT22细胞系增殖和基因表达的影响

doi:10.3969/j.issn.1674-490X.2022.04.001

医学研究与教育 ›› 2022, Vol. 39 ›› Issue (4): 1-7.DOI: 10.3969/j.issn.1674-490X.2022.04.001

• 基础医学 • 下一篇

RG108对HT22细胞系增殖和基因表达的影响

姜乐,王晓兵,贺尔姝,郑晓烨,龚志婷

大理大学基础医学院人体解剖教研室, 云南大理 671000

收稿日期:2022-02-19 出版日期:2022-08-25 发布日期:2022-08-25
通讯作者: 龚志婷(1990—),女,云南保山人,实验师,博士,硕士生导师,主要从事神经生物学方向研究。E-mail: gzhting@foxmail.com
作者简介:姜乐(1990—),女,河北石家庄人,在读硕士。
基金资助:
国家自然科学基金-地区项目(81960255);云南省基础研究专项云南省基础研究项目-青年项目(202001AU070051)

Effect of RG108 on proliferation and gene expression of HT22 cell line

JIANG Le,WANG Xiaobing,HE Ershu,ZHENG Xiaoye,GONG Zhiting

Department of Human Anatomy, School of Basic Medicial Sciences, Dali University, Dali 671000, Yunnan

Received:2022-02-19 Online:2022-08-25 Published:2022-08-25

摘要/Abstract

摘要： 目的探讨DNA甲基转移酶抑制剂RG108对体外培养的小鼠海马神经元细胞系HT22细胞的影响。方法 DNA甲基转移酶抑制剂RG108浓度设置为0.5、5、50 μmol/L,对体外培养的HT22海马神经元细胞进行干预,CCK-8检测细胞活力;利用RT-qPCR检测细胞中下游基因的表达情况。结果 CCK-8实验表明,50 μmol/L RG108处理HT22细胞48、72 h后可以促进细胞增殖,差异有统计学意义(P<0.05)。RT-qPCR结果证明,50 μmol/L RG108处理HT22细胞后突触可塑性相关基因nr1、reln表达降低,差异有统计学意义(P<0.05)。结论 DNA甲基转移酶抑制剂RG108能促进小鼠海马神经元细胞系HT22细胞增殖并调控神经可塑性相关基因表达。且RG108可能会影响突触可塑性,对突触可塑性相关行为(如记忆)的形成造成影响。

关键词: 海马神经元, 表观遗传学, DNA甲基化, RG108

Abstract: Objective To investigate the effect of DNA methyltransferase inhibitor RG108,on HT22 cells,a mouse hippocampal neuronal cell line cultured in vitro.Methods HT22 hippocampal neuronal cells cultured in vitro were treated with DNA methyltransferase inhibitor RG108 at concentrations of 0.5,5,and 50 μmol/L,and the cell viability was detected with CCK-8,and the expression of middle and downstream genes in the cells was detected using RT-qPCR.Results CCK-8 assay showed that 50 μmol/L RG108 could promote the proliferation of HT22 cells after 48 and 72 hours and the difference was statistically significant(P<0.05).RT-qPCR results demonstrated that the expression of synaptic plasticity-related genes nr1 and reln decreased in HT22 cells treated with 50 μmol/L RG108,and the difference was statistically significant(P<0.05).Conclusion DNA methyl transferase inhibitor RG108 can promote the proliferation of mouse hippocampal cell line HT22 cells and regulate the expression of neuroplasticity-related genes.Moreover,RG108 may affect synaptic plasticity,which may influence synaptic plasticity-related behaviors such as memory formation.

Key words: hippocampal neurons, epigenetics, DNA methylation, RG108

中图分类号:

姜乐,王晓兵,贺尔姝,郑晓烨,龚志婷. RG108对HT22细胞系增殖和基因表达的影响[J]. 医学研究与教育, 2022, 39(4): 1-7.

JIANG Le,WANG Xiaobing,HE Ershu,ZHENG Xiaoye,GONG Zhiting. Effect of RG108 on proliferation and gene expression of HT22 cell line[J]. Journal of Hebei Medical College for Continuing Education, 2022, 39(4): 1-7.

参考文献

[1] MAIO V D.Regulation of information passing by synaptic transmission:a short review[J].Brain Res,2008,1225:26-38.DOI: 10.1016/j.brainres.2008.06.016.
[2] CUI D,XU X R.DNA methyltransferases,DNA methylation,and age-associated cognitive function[J].Int J Mol Sci,2018,19(5):1315.DOI: 10.3390/ijms19051315.
[3] DAY J J,CHILDS D,GUZMAN-KARLSSON M C,et al.DNA methylation regulates associative reward learning[J].Nat Neurosci,2013,16(10):1445-1452.DOI: 10.1038/nn.3504.
[4] DAY J J,SWEATT J D.DNA methylation and memory formation[J].Nat Neurosci,2010,13(11):1319-1323.DOI: 10.1038/nn.2666.
[5] FENG J,FOUSE S,FAN G P.Epigenetic regulation of neural gene expression and neuronal function[J].Pediatr Res,2007,61(5 Pt 2):58R-63R.DOI: 10.1203/pdr.0b013e3180457635.
[6] SALES A J,MACIEL I S,SUAVINHA A C D R,et al.Modulation of DNA methylation and gene expression in rodent cortical neuroplasticity pathways exerts rapid antidepressant-like effects[J].Mol Neurobiol,2021,58(2):777-794.DOI: 10.1007/s12035-020-02145-4.
[7] MUN ~OZ P,ESTAY C,DÍAZ P,et al.Inhibition of DNA methylation impairs synaptic plasticity during an early time window in rats[J].Neural Plast,2016,2016:4783836.DOI: 10.1155/2016/4783836.
[8] LIU R,WU X M,HE X,et al.Contribution of DNA methyltransferases to spared nerve injury induced depression partially through epigenetically repressing Bdnf in Hippocampus:reversal by ketamine[J].Pharmacol Biochem Behav,2021,200:173079.DOI: 10.1016/j.pbb.2020.173079.
[9] MORRIS M J,NA E S,AUTRY A E,et al.Impact of DNMT1 and DNMT3a forebrain knockout on depressive- and anxiety like behavior in mice[J].Neurobiol Learn Mem,2016,135:139-145.DOI: 10.1016/j.nlm.2016.08.012.
[10] LYKO F,BROWN R.DNA methyltransferase inhibitors and the development of epigenetic cancer therapies[J].J Natl Cancer Inst,2005,97(20):1498-1506.DOI: 10.1093/jnci/dji311.
[11] RONDELET G,FLEURY L,FAUX C,et al.Inhibition studies of DNA methyltransferases by maleimide derivatives of RG108 as non-nucleoside inhibitors[J].Future Med Chem,2017,9(13):1465-1481.DOI: 10.4155/fmc-2017-0074.
[12] ZHENG Z W,ZENG S,LIU C,et al.The DNA methylation inhibitor RG108 protects against noise-induced hearing loss[J].Cell Biol Toxicol,2021,37(5):751-771.DOI: 10.1007/s10565-021-09596-y.
[13] FENG L F,LOU J L.DNA methylation analysis[J].Methods Mol Biol Clifton N J,2019,1894:181-227.DOI: 10.1007/978-1-4939-8916-4_12.
[14] CUNHA C,TODOROV G,ASHUROV D,et al.DNA methyltransferase inhibitor successfully treats obsessive-compulsive disorder in various mouse models[J].Neurol Neurobiol,2021:1-13.DOI: 10.31487/j.nnb.2021.01.02.
[15] MILLER C A,SWEATT J D.Covalent modification of DNA regulates memory formation[J].Neuron,2007,53(6):857-869.DOI: 10.1016/j.neuron.2007.02.022.
[16] FENG J,ZHOU Y,CAMPBELL S L,et al.Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons[J].Nat Neurosci,2010,13(4):423-430.DOI: 10.1038/nn.2514.
[17] OLIVEIRA A M M,HEMSTEDT T J,BADING H.Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities[J].Nat Neurosci,2012,15(8):1111-1113.DOI: 10.1038/nn.3151.
[18] HEMSTEDT T J,LATTAL K M,WOOD M A.Reconsolidation and extinction:using epigenetic signatures to challenge conventional wisdom[J].Neurobiol Learn Mem,2017,142(Pt A):55-65.DOI: 10.1016/j.nlm.2017.01.007.
[19] JI S J,DING X,JI J,et al.Cranial irradiation inhibits hippocampal neurogenesis via DNMT1 and DNMT3A[J].Oncol Lett,2018,15(3):2899-2904.DOI: 10.3892/ol.2017.7643.
[20] DONG E B,LOCCI V,GATTA E,et al.N-phthalyl-l-tryptophan(RG108),like clozapine(CLO),induces chromatin remodeling in brains of prenatally stressed mice[J].Mol Pharmacol,2019,95(1):62-69.DOI: 10.1124/mol.118.113415.
[21] ARGYROUSI E K,DE NIJS L,LAGATTA D C,et al.Effects of DNA methyltransferase inhibition on pattern separation performance in mice[J].Neurobiol Learn Mem,2019,159:6-15.DOI: 10.1016/j.nlm.2019.02.003.

RG108对HT22细胞系增殖和基因表达的影响

Effect of RG108 on proliferation and gene expression of HT22 cell line

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 2

编辑推荐

Metrics

本文评价

[1]	朱波,刘经纬,豆建,李日恒. 表观遗传药物在结直肠癌治疗中的研究进展[J]. 医学研究与教育, 2020, 37(4): 13-19.
[2]	赵鹏辉,赵峥辉,刘宣辰,田园,葛少钦. 高通量测序技术在生殖遗传学检测中的应用[J]. 医学研究与教育, 2018, 35(1): 46-50.