Carcinogenesis, Teratogenesis & Mutagenesis

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

HU Ming12,HAN Chun-guang1,CAO Dong3,YU Ji-Yao12,*, WANG Kai1,KANG Xiao-ling4,LIU Yong-xue1,*   

  1. (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

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