王若楠,
牛小影,
王睿珺,
秦畅,
李亚晨,
刘晓晖,
邵静
大连医科大学公共卫生学院, 大连市血液病重点实验室, 辽宁省造血干细胞移植医学中心, 辽宁省造血干细胞移植临床转化医学研究重点实验室, 大连 116044

作者简介: 王若楠(1993-),女,硕士,研究方向为环境污染与出生缺陷,E-mail:daisywrn@126.com.

基金项目: 国家自然科学基金(81302400)；中国博士后科学基金(2016M591438)；大连市科技之星项目(2016RQ044)；大连医科大学本科教学改革研究立项项目(DYLX16053)


中图分类号: X171.5

Role of Epigenetic Modification in the PFOS Neurotoxicity—A Study in the Rat Primary Astrocytes

Wang Ruonan,
Niu Xiaoying,
Wang Ruijun,
Qin Chang,
Li Yachen,
Liu Xiaohui,
Shao Jing
School of Public Health, Dalian Medical University, Dalian Key Laboratory of Hematology, Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, Dalian 116044, China

CLC number: X171.5

-->

摘要
HTML全文
图(0)表(0)
参考文献(0)
相关文章
施引文献
资源附件(0)
访问统计

摘要:脑源性神经营养因子(BDNF)甲基化在全氟辛烷磺酸(PFOS)神经毒性中的作用已证实，但表观遗传修饰中其他调控因子在PFOS对星形胶质细胞毒性中的影响仍有待探索。本文以大鼠原代星形胶质细胞为体外生物体系，建立24 h PFOS(0、25、50和100 μmol·L^-1)暴露模型，通过观察PFOS暴露对星形胶质细胞表观遗传调控主要分子DNA甲基化酶(DNMTs)、组蛋白去乙酰化酶(HDACs)和小泛素化修饰物(SUMOs)的影响，初步明确表观遗传调控机制参与PFOS神经毒性作用。采用Hoechst 33258检测细胞凋亡，利用ELISA试剂盒检测HDACs含量，以实时荧光定量PCR考察DNMTs、HDACs和SUMOs基因表达。结果显示，星形胶质细胞暴露于一定浓度PFOS(≥25 μmol·L^-1)时产生凋亡现象(P<0.05)，HDACs含量升高(P>0.05)，且DNMT1、HDAC1/2/4与SUMO-1的基因表达显著升高(P<0.05)；而当PFOS浓度高于50 μmol·L^-1时，可显著诱导DNMT3A、SUMO-2的基因表达(P<0.05)；DNMT3B在PFOS≥25 μmol·L^-1时，其基因表达具有升高趋势，但不具统计学显著性(P>0.05)。结果表明，PFOS可以影响星形胶质细胞的表观遗传修饰；表观遗传修饰可能是PFOS神经毒性作用机制之一。
关键词: PFOS/
星形胶质细胞/
表观遗传/
神经毒性

Abstract:Though the role of DNA methylation for brain-derived neurotrophic factor (BDNF) in PFOS-induced neurotoxicity has been confirmed, the other related molecular of epigenetics in PFOS-induced neurotoxicity in astrocytes is needed to be explored. In the present study, the model of PFOS exposure with 0, 25, 50, 100 μmol·L^-1 for 24 h was built through primary cultured astrocyte from Wistar rats. And the main molecular in epigenetics, such as DNA methyltransferase (DNMTs), histone deacetylase (HDACs), small ubiquitination (SUMOs) was evaluated. Then the cell apoptosis was detected by Hoechst 33258, the content of HDACs was evaluated by ELISA kit, and the gene expressions of DNMTs, HDACs and SUMOs were detected by real time quantitative PCR. The results showed that PFOS (≥25 μmol·L^-1) could induce apoptosis in the primary cultured astrocytes (P<0.05), increase the content of HDACs (P>0.05). Further analysis showed that PFOS (≥25 μmol·L^-1) significantly increased the expressions of DNMT1, HDAC1/2/4 and SUMO-1 mRNA (P<0.05). The expressions of DNMT3A and SUMO-2 mRNA were also increased in PFOS (≥50 μmol·L^-1) exposure group (P<0.05). And there was an increase trend for DNMT3B gene expression (P>0.05). Generally, the results showed that PFOS could influence the epigenetic modification in astrocytes. The present study might give a clue for the mechanism of neurotoxicity induced by PFOS.
Key words:PFOS/
astrocytes/
epigenetics/
neurotoxicity.