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Toxicol In Vitro. 2017 Aug;42:299-307. doi: 10.1016/j.tiv.2017.05.012. Epub 2017 May 13.

Acot1 is a sensitive indicator for PPARα activation after perfluorooctanoic acid exposure in primary hepatocytes of Sprague-Dawley rats.

Author information

1
Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China; Department of Laboratory Medicine, Bengbu Medical College, Bengbu 233030, PR China.
2
Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
3
Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China. Electronic address: daijy@ioz.ac.cn.

Abstract

Perfluorooctanoic acid (PFOA) is one of the most commonly detected and persistent perfluoroalkyl substances (PFASs) found in the environment. We found that cell viability and intracellular oxidant stress increased in primary rat hepatocytes exposed to PFOA (100μM PFOA, 24h), and mitochondrial superoxide increased from 6.25μM PFOA treatment group. To screen for sensitive indicators in mRNA level, we investigated global transcriptome profile alteration after PFOA exposure using RNA-sequencing (RNA-seq) in primary rat hepatocytes, and identified 177 gene transcripts (158 upregulated, 19 downregulated) as significantly changed after exposure to 100μM of PFOA for 24h (fold change ≥2, FDR<0.05). Quantitative PCR (qPCR) and RNA-fluorescence in situ hybridization (RNA-FISH) assays were conducted after PFOA treatment at various doses (0, 0.4, 1.56, 6.25, 25, and 100μM) and times (6, 12, 18, 24, 48, and 96h). Acot1 transcripts increased significantly in the 100μM PFOA group (4500-fold) after 24h of exposure, and increased remarkably for all time points (24, 48, 72 and 96h) after exposure to 6.25μM. Acot1 also responded to lower PFOA doses, with a significant increase found after exposure to 0.4μM for 96h. These results imply Acot1 could serve as a sensitive indicator for PPARα activation after PFOA exposure in primary rat hepatocytes.

KEYWORDS:

Acot1; Hepatocyte; PPARα; Perfluorooctanoic acid

PMID:
28511854
DOI:
10.1016/j.tiv.2017.05.012
[Indexed for MEDLINE]

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