College of Life and Environmental Sciences, Hangzhou Normal University, Xuelin Road 16#, Xiasha Gaojiao Dongqu, Hangzhou, Zhejiang Province 310036, China; Guangzhou Key Laboratory of Environmental Exposure and Health, School of Environment, Jinan University, Guangzhou 510632, China; Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, Hangzhou Normal University, Hangzhou, Zhejiang Province 310036, China.
College of Life and Environmental Sciences, Hangzhou Normal University, Xuelin Road 16#, Xiasha Gaojiao Dongqu, Hangzhou, Zhejiang Province 310036, China.
Ecotoxicol Environ Saf. 2019 Jan 15;167:29-35. doi: 10.1016/j.ecoenv.2018.09.120. Epub 2018 Oct 4.
Perfluorooctanoic acid (PFOA) is a perfluorinated compound that is widely distributed, is persistent in the environment, and has a low-level chronic exposure effect on human health. The aim of this study was to investigate the peroxisome proliferator activated receptors γ (PPARγ) and the sterol regulatory element-binding protein 2 (SREBP2) signaling pathways in regulating the lipid damage response to PFOA in the livers of amphibians. Male and female frogs (Rana nigromaculata) were exposed to 0, 0.01, 0.1, 0.5 and 1 mg/L PFOA. After treatment, we evaluated the pathological changes in the liver by Oil Red O, staining and examined the total cholesterol (T-CHO) and triglyceride (TG) contents. The mRNA expression levels of PPARγ, Fatty acid synthase (FAS), Acetyl-CoA carboxylase (ACC), Glycerol-3-phosphate acyltransferase (GPAT), SREBP2 and 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The administration of PFOA caused marked lipid accumulation damage in the amphibian livers. The T-CHO contents were elevated significantly after PFOA treatment; these results show a dose-dependent manner in both sexes. The TG content showed a significant increase in male livers, while it was elevated significantly in female livers. The RT-PCR results showed that the mRNA expression levels of PPARγ, ACC, FAS, GPAT, SREBP2 and HMG-CoA were significantly dose-dependently increased in the PFOA-treated groups compared with those of the control group. Our results demonstrated that PFOA-induced lipid accumulation also affected the expression levels of genes FAS, ACC, GPAT and HMG-CoA in the PPARγ and SREBP2 signaling pathways in the liver. These finding will provide a scientific theoretical basis for the protection of Rana nigromaculata against PFOA effects.
全氟辛酸(PFOA)是一种全氟化合物,广泛分布,在环境中持久存在,对人类健康具有低水平的慢性暴露效应。本研究旨在探讨过氧化物酶体增殖物激活受体γ(PPARγ)和固醇调节元件结合蛋白 2(SREBP2)信号通路在调节两栖动物肝脏中 PFOA 诱导的脂质损伤反应中的作用。雄性和雌性青蛙(Rana nigromaculata)暴露于 0、0.01、0.1、0.5 和 1mg/L 的 PFOA 中。处理后,我们通过油红 O 染色评估肝脏的病理变化,并检测总胆固醇(T-CHO)和甘油三酯(TG)含量。通过定量实时聚合酶链反应(qRT-PCR)测量 PPARγ、脂肪酸合酶(FAS)、乙酰辅酶 A 羧化酶(ACC)、甘油-3-磷酸酰基转移酶(GPAT)、SREBP2 和 3-羟-3-甲基戊二酰辅酶 A(HMG-CoA)的 mRNA 表达水平。PFOA 处理导致两栖动物肝脏明显的脂质积累损伤。T-CHO 含量在 PFOA 处理后显著升高;这些结果在两性中均表现出剂量依赖性。TG 含量在雄性肝脏中显著增加,而在雌性肝脏中显著增加。RT-PCR 结果表明,与对照组相比,PFOA 处理组中 PPARγ、ACC、FAS、GPAT、SREBP2 和 HMG-CoA 的 mRNA 表达水平均显著剂量依赖性增加。我们的结果表明,PFOA 诱导的脂质积累也影响了 PPARγ 和 SREBP2 信号通路中 FAS、ACC、GPAT 和 HMG-CoA 基因的表达水平。这些发现将为保护黑斑蛙免受 PFOA 影响提供科学理论依据。