氢醌对骨髓间充质干细胞PARP-1和DNA甲基转移酶基因和蛋白表达的影响

doi:10.13217/j.scjpm.2018.0201

华南预防医学 ›› 2018, Vol. 44 ›› Issue (3): 201-205.doi: 10.13217/j.scjpm.2018.0201

• 论著 • 下一篇

氢醌对骨髓间充质干细胞PARP-1和DNA甲基转移酶基因和蛋白表达的影响

高羽亭^1，2，杜进林^1，2，张轶³，孙铭薇^1，2，杨慧^1，2

1.广东医科大学公共卫生学院，广东东莞523808；2.东莞市环境医学重点实验室；3.广东医科大学第二临床学院

收稿日期:2018-02-12 修回日期:2018-02-12 出版日期:2018-07-03 发布日期:2018-07-20
作者简介:高羽亭(1982—)，女，博士研究生，讲师，主要从事毒理学研究工作
基金资助:
国家自然科学基金（81703266）；广东省自然科学基金（2015A030310532）；广东省医学科研基金（A2016246）；广东医科大学科研基金（2XB13012）

Effect of hydroquinone on the expression of poly (ADP-ribose) polymerase-1 and DNA methyltransferases and protein in bone mesenchymal stem cells

GAO Yu-ting^1,2, DU Jin-lin^1,2, ZHANG Yi³, SUN Ming-wei^1,2, YANG Hui^1,2

1. School of Public Health, Guangdong Medical University，Dongguan 523808,China; 2.Dongguan Key Laboratory of Environmental Medicine; 3. The Second School of Clinical Medicine, Guangdong Medical University

Received:2018-02-12 Revised:2018-02-12 Online:2018-07-03 Published:2018-07-20

摘要/Abstract

摘要： 目的探讨氢醌(HQ)诱导DNA甲基化改变的分子机制。方法用磷酸盐缓冲液(PBS)溶解HQ，以PBS处理组作为对照，采用实时荧光定量-聚合酶链反应和蛋白质免疫印记法检测2.5、5.0、10.0、20.0 μmol/L HQ染毒骨髓间充质干细胞(BMMSCs)聚腺苷酸二磷酸核糖转移酶-1（PARP-1）和DNA甲基转移酶DNMT1、DNMT3a和DNMT3b基因和蛋白的表达。结果PARP-1、DNMT1 基因和蛋白表达水平均随HQ染毒剂量的增加而升高，呈剂量-效应关系，基因表达的回归方程分别为y ?=0.030 x+1.283，y ?=0.075 x+1.088，蛋白表达的回归方程分别为y ?=0.025 x+1.234， y ?=0.043 x+1.097，DNMT3a基因和蛋白表达水平随剂量增加而降低，呈剂量-效应关系，基因和蛋白表达的回归方程分别为y ?=-0.040x+1.151；y ?=-0.012x+1.021。结论HQ暴露导致基因组DNA甲基化的改变可能与DNA甲基转移酶表达异常有关，且PARP-1可能参与了HQ暴露致DNA低甲基化的过程。

Abstract: ObjectiveTo explore the molecular mechanism of DNA methylation alteration induced by hydroquinone (HQ). MethodsHQ was prepared by PBS buffer and bone marrow mesenchymal stem cells (BMMSCs) were treated with PBS served as the control. The genes and protein expression of PARP-1 and DNA methyltransferase ( DNMTs) , DNMT1, DNMT3a and DNMT3b in BMMSCs exposed to 2.5, 5.0, 10.0, and 20.0 μmol?L-1 HQ were tested by real-time fluorescence quantitive PCR and Western blotting.ResultsThe genes and protein expression of PARP-1 and DNMT1 were increased in a dose-dependent manner. The regression equations of genes were y ?=0.030 x+1.283 and y ?=0.075 x+1.088. The regression equations of protein were y ?=0.025 x+1.234 and y ?=0.043 x+1.097. But the gene and protein expressions of DNMT3a were decreased in a dose-dependent manner. The regression equations of gene and protein were y ?=-0.040 x+1.151 and y ?=-0.012 x+1.021, respectively.ConclusionThe change of global DNA methylation induced by HQ may be associated with the deregulated expressions of DNMTs, and PARP-1 may participate in global DNA hypomethylation induced by HQ.

中图分类号:

R114

高羽亭，杜进林，张轶，孙铭薇，杨慧. 氢醌对骨髓间充质干细胞PARP-1和DNA甲基转移酶基因和蛋白表达的影响[J]. 华南预防医学, 2018, 44(3): 201-205.

GAO Yu-ting, DU Jin-lin, ZHANG Yi, SUN Ming-wei, YANG Hui. Effect of hydroquinone on the expression of poly (ADP-ribose) polymerase-1 and DNA methyltransferases and protein in bone mesenchymal stem cells[J]. S China J Prev Med, 2018, 44(3): 201-205.

参考文献

［1］North M,Shuga J,Fromowitz M,et al.Modulation of Ras signaling alters the toxicity of hydroquinone,a benzene metabolite and component of cigarette smoke［J］.BMC Cancer,2014,14（1）:6. 
［2］田薇,夏昭林.苯毒性作用表观遗传学研究进展［J］.工业卫生与职业病,2016,42(4):310-312. 
［3］Rhee I，Bachman KE,Park BH,et al.DNMT 1 and DNMT 3b cooperate to silence genes in human cancer cells［J］.Nature,2002,416(6880)：552-556. 
［4］沈双,路则明,金景姬,等.表观遗传学修饰的遗传模式及其研究进展［J］.科学通报,2016,61(36):3878-3886. 
［5］Liu Q,Yang L,Gong C,et al.Effects of long-term low-dose formaldehyde exposure on global genomic hypomethylation in 16HBE cells［J］.Toxicology Letters,2011,205(3): 235-240. 
［6］Ling XX,Liu JX,Yun L,et al.Poly(ADP-ribosyl)ation of apoptosis antagonizing transcription factor involved in hydroquinone-induced DNA damage response［J］.Biomedical & Environmental Sciences,2016,29(1):80-84. 
［7］Mendez-Ferrer S,Michurina TV,Ferraro F,et al.Mesenchymal and haematopoietic stem cells form a unique bone marrow niche［J］.Nature,2010,466(7308)：829-834. 
［8］高羽亭,刘林华,黄明元,等.低剂量氢醌对大鼠骨髓间充质干细胞生物学性状及PARP-1表达影响［J］.吉林大学学报(医学版)，2012,38(2):216-220. 
［9］高羽亭,杜进林,杨慧,等.沉默PARP-1对氢醌所致大鼠骨髓间充质干细胞凋亡影响［J］.中国职业医学,2017,44(1):36-41. 
［10］Liu L,Ling X,Liang H,et al.Hypomethylation mediated by decreased DNMTs involves in the activation of proto-oncogene MPL in TK6 cells treated with hydroquinone［J］.Toxicol Lett,2012,209(3):239-245. 
［11］Ji Z,Zhang L,Peng V,et al.A comparison of the cytogenetic alterations and global DNA hypomethylation induced by the benzene metabolite,hydroquinone，with those induced by melphalan and etoposide［J］.Leukemia,2010,24(5): 986-991. 
［12］王晶晶,马慧敏,李宝才,等.苯代谢物氢醌对人体肝细胞内DNA甲基转移酶基因和蛋白表达的影响［J］.昆明理工大学学报(自然科学版),2013,38(5):90-95. 
［13］徐龙妹,刘嘉贤,云林,等.氢醌致DNA甲基化改变及可能机制［J］.环境与职业医学,2016，33(7):717-722. 
［14］Ting AH,Jair KW,Schuebel K,et al.Differential requirement for DNA methyltransferase 1 in maintaining human cancer cell gene promoter hypermethylation［J］.Cancer Res,2006,66(2):729-735. 
［15］Robert ME,Morin S,Beaulieu N,et al.DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells［J］.Nat Genet,2003,33(1):61-65. 
［16］Rhee I,Jair KW,Yen RW,et al.CpG methylation is maintained in human cancer cells lacking DNMT1［J］.Nature,2000,404(6781):1003-1007. 
［17］Gao Q,Steine EJ,Barrasa MI,et al.Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression［J］.Proc Natl Acad Sci USA,2011,108(44):18061-18066. 
［18］高羽亭,杨慧.PARP-1沉默对骨髓间充质干细胞凋亡的影响［J］.中国老年学杂志,2017,37(1):575-577. 
［19］Wang Y,An R,Umanah GK,et al.A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1［J］.Science,2016,354(6308):82-96. 
［20］凌晓璇,温桥生,杜谕君,等.多聚聚合酶-1在氢醌诱导的DNA损伤应答中的作用及其机制［J］.职业与健康,2015,31 (14):1906-1909. 
［21］Sha Y,Yang Z,Zhou W,et al.Role of poly（ADP-ribose）polymerase 1 in DNA methylation changes induced by hydroquinone in human bronchial epithelial cell［J］.Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi,2014,32(3):181-185. 
［22］索美芳,沈佐军.肿瘤基因启动子区异常甲基化与肿瘤的发生［J］.分子诊断与治疗杂志,2013,5(4):274-278. 
［23］凌晓璇,梁海荣,黄明元,等.氢醌对DNA甲基转移酶表达的影响［J］.实用预防医学,2012,19(7):961-963.

[1]	蔡君华, 张波, 劳文艳, 任超, 范子轩. 复合营养素对PM_2.5所致大鼠急性肺部氧化应激和炎症损伤的影响[J]. 华南预防医学, 2022, 48(8): 907-911.
[2]	唐娇, 李文立, 胡帅尔, 杨美玲, 茅莉娜, 方苑, 张紫虹. 蒽醌暴露对秀丽隐杆线虫的毒性作用[J]. 华南预防医学, 2021, 47(11): 1375-1378.
[3]	马艳，李梦承，李文学，杨光宇，殷花，章霞，李军涛，吴锦银，朱伟，张波. 全氟辛烷磺酸诱导HepG2细胞凋亡的线粒体损伤机制研究[J]. 华南预防医学, 2016, 42(1): 6-10.
[4]	杨美玲，何云，李欣. 白杨素抗肿瘤作用及分子机制研究进展[J]. 华南预防医学, 2015, 41(6): 545-548.
[5]	唐娇，赵敏，谭剑斌，陈壁锋，黄俊明，杨杏芬. 三七的经口急性毒性及亚慢性毒性研究[J]. 华南预防医学, 2015, 41(6): 521-526.
[6]	张可欣, 黄鹭, 黄晓晖, 赵敏, 杨杏芬, 朱焕容, 张梦梦, 谭剑斌. 广东凉茶提取物对兔红细胞膜氧化损伤保护作用研究[J]. 华南预防医学, 2019, 45(1): 21-25.

氢醌对骨髓间充质干细胞PARP-1和DNA甲基转移酶基因和蛋白表达的影响

Effect of hydroquinone on the expression of poly (ADP-ribose) polymerase-1 and DNA methyltransferases and protein in bone mesenchymal stem cells

PDF (PC)

赞

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 6

Metrics

本文评价

推荐阅读 0