全氟辛酸对HK-2 细胞的毒性及对α-酮戊二酸盐受体1 表达的影响

doi:10.3969/j.issn.1004-616x.2013.06.001

癌变·畸变·突变

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全氟辛酸对HK-2 细胞的毒性及对α-酮戊二酸盐受体1 表达的影响

胡明¹，²,韩春光¹,曹冬³,虞积耀¹，²，*,王恺¹,康筱玲⁴,刘永学¹，*

( 1. 军事医学科学院放射与辐射医学研究所，北京 100850； 2. 海军总医院，海战伤救治研究中心，北京 100048； 3. 中国科学院生态环境研究中心，环境化学与生态毒理学国家重点实验室，北京 100085； 4. 海军总医院病理科，北京 100048 )

收稿日期:2013-09-12 修回日期:2013-09-25 出版日期:2013-11-30 发布日期:2013-11-30
通讯作者: 刘永学， E-mail： liuyx@ bmi.ac.cn；虞积耀，Tel：010-66932252
作者简介:胡明(1970- )，男，辽宁省朝阳市人，博士研究生，主治医师，研究方向：病理学与病理生理学。Tel： 010-66958552；E-mail： humingminghu@163.com
基金资助:
国家自然科学基金项目(30973575)

Toxicity of perfluorooctanoic acid to HK-2 cells and its effect on the expression of oxogluatarate receptor 1

HU Ming¹，²，HAN Chun-guang¹，CAO Dong³，YU Ji-Yao¹，²，*， WANG Kai¹，KANG Xiao-ling⁴，LIU Yong-xue¹，*

(1. Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850; 2. Naval Battle Wound Care and Treatment Research Center, Navy General Hospital，Beijing 100048; 3. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, Beijing 100085; 4. Department of Pathology, Navy General Hospital, Beijing 100048, China)

Received:2013-09-12 Revised:2013-09-25 Online:2013-11-30 Published:2013-11-30
Contact: LIU Yong-xue， E-mail： liuyx@ bmi.ac.cn；YU Ji-yao，Tel：010-66932252

摘要/Abstract

摘要：

目的： 研究全氟辛酸(perfluorooctanoic acid， PFOA)对HK-2细胞的毒性，及其对α-酮戊二酸盐受体1(oxoglutarate receptor 1，OXGR1)表达的影响。方法：采用MTT法检测不同浓度(0、0.1、1、10、100、1 000 μmol/L)PFOA对HK-2细胞增殖的影响。RT-PCR法检测0、100、300 μmol/L PFOA对HK-2细胞中OXGR1、琥珀酸盐受体1(succinate receptor 1，SUCNR1)、缺氧诱导因子1α(hypoxia-inducible factor 1α，HIF-1α)mRNA表达的影响。当PFOA为300或0 μmol/L时，采用MTT法检测不同浓度(0、1、10、100、1 000、10 000 μmol/L) OXGR1配基α-酮戊二酸钠(α-ketoglutarate sodium， AKG)对HK-2细胞增殖的影响。流式细胞术检测300 μmol/L PFOA和100 μmol/L AKG共同作用HK-2细胞48 h后细胞的凋亡情况。结果：在培养24 h条件下，PFOA达1 000 μmol/L时可表现出毒性作用(P<0.01)。在培养48或72 h条件下，PFOA≥100 μmol/L时表现出毒性作用(P<0.01)。RT-PCR结果显示，PFOA可上调HK-2细胞中OXGR1 mRNA表达(P<0.01)，但对SUCNR1及HIF-1α mRNA表达无明显影响(P>0.05)。MTT及流式细胞术检测结果显示，AKG与PFOA可协同作用抑制HK-2细胞增殖(P<0.01)并诱导细胞凋亡(P<0.05)。 结论：PFOA对HK-2细胞具有增殖抑制作用，并可上调细胞OXGR1 mRNA表达；PFOA可诱发HK-2细胞凋亡；AKG可与PFOA产生协同作用，该协同作用可能与OXGR1有关。

关键词: 全氟辛酸, α-酮戊二酸盐受体1, α-酮戊二酸, HK-2细胞

Abstract:

OBJECTIVE：To explore the toxicity of perfluorooctanoic acid (PFOA) to HK-2 cells，and its effect on the expression of oxoglutarate receptor 1 (OXGR1) in HK-2 cells. METHODS：The effect of different concentrations of PFOA on HK-2 cells proliferation was examined by MTT assay. The effect of PFOA (0，100，300 μmol/L) on mRNA expression of OXGR1，succinate receptor 1 (SUCNR1) and hypoxia-inducible factor 1α (HIF-1α) in HK-2 cells were evaluated by RT-PCR. The effect of different concentrations (0，1，10，100，1 000，10 000 μmol/L) of α-ketoglutarate sodium (AKG) on HK-2 cell proliferation with or without PFOA (300 μmol/L) was assayed by MTT method. Apoptoses of HK-2 cells after 48 h of culture in medium with PFOA (300 μmol/L) and AKG (100 μmol/L) were examined by flow cytometry. RESULTS：1 000 μmol/L of PFOA exhibited toxicity after 24 h of culture (P<0.01). PFOA(≥100 μmol/L) exhibited toxicity after 48 h or 72 h of culture (P<0.01). RT-PCR showed that PFOA upregulated OXGR1 mRNA expression in HK-2 cells，but it had no effects on the expressions of SUCNR1 and HIF-1α mRNA. Interaction of AKG and PFOA inhibited proliferation of HK-2 cells (P<0.001) and induced apoptosis (P<0.05)， which were measured by MTT and flow cytometry. CONCLUSION： PFOA could inhibit the proliferation of HK-2 cells，and upregulate mRNA expression of OXGR1. PFOA could induce apoptosis of HK-2 cells；interaction of AKG and PFOA could also induce apoptosis，and whether this interaction is OXGR1 dependant remains to be further verified.

Key words: perfluorooctanoic acid, oxogluatarate receptor 1, α-ketoglutarate, HK-2 cells

胡明,韩春光,曹冬,虞积耀,王恺,康筱玲,刘永学. 全氟辛酸对HK-2 细胞的毒性及对α-酮戊二酸盐受体1 表达的影响[J]. 癌变·畸变·突变, doi: 10.3969/j.issn.1004-616x.2013.06.001.

HU Ming，HAN Chun-guang，CAO Dong，YU Ji-Yao， WANG Kai，KANG Xiao-ling，LIU Yong-xue. Toxicity of perfluorooctanoic acid to HK-2 cells and its effect on the expression of oxogluatarate receptor 1[J]. Carcinogenesis, Teratogenesis & Mutagenesis, doi: 10.3969/j.issn.1004-616x.2013.06.001.

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全氟辛酸对HK-2 细胞的毒性及对α-酮戊二酸盐受体1 表达的影响

Toxicity of perfluorooctanoic acid to HK-2 cells and its effect on the expression of oxogluatarate receptor 1

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