期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 381, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2019.114716
关键词
Perfluorooctanoic acid; primary cardiomyocyte; intracellular calcium; in ovo gene silencing; Wnt5a/Frizzled2
资金
- National Natural Science Foundation of China [81502835, 81872591]
Perfluorooctanoic acid (PFOA) is a widespread persistent organic pollutant and may induce developmental toxicities, including developmental cardiotoxicity. To explore the potential mechanism of developmental cardiotoxicity induced by PFOA exposure, chicken embryo primary cardiomyocytes were extracted either from chicken embryos pretreated with PFOA (2 mg/kg), or from untreated embryos and then directly exposed cells to PFOA (1, 10, 30 or 100 mu g/ml) in culture. Additionally, peroxisome proliferator activated receptor alpha (PPAR alpha) silencing lentivirus was applied to the embryos on embryonic day (ED2). Cell viability was measured with CCK-8 kit, morphology was assessed with hematoxylin and eosin staining, and intracellular Ca2+ concentrations were determined with Fluo-4 AM probe. Western blotting was utilized to confirm PPAR alpha silencing efficiency and the protein abundance of Wnt5a and Frizzled2. The results indicated that both PFOA pretreatment and direct exposure decreased primary cardiomyocyte viability, altered cell morphology and increased intracellular Ca2+ concentrations. While L-carnitine co-treatment effectively abolished such changes, PPAR alpha silencing only abolished most of the changes in PFOA pretreatment group, but not in cells directly exposed to relatively high doses of PFOA. The protein abundance of Wnt5a and Frizzled2 was increased by PFOA pretreatment, while direct exposure to PFOA increased Frizzled2 abundance but decreased Wnt5a abundance. PPAR alpha silencing resulted in over 50% decrease of PPAR alpha expression level, which abolished the Wnt5a/Frizzled2 expression alterations following PFOA exposure. In conclusion, PFOA-induced primary cardiomyocyte toxicity is associated with PPAR alpha and Wnt5a/Frizzled2, in which PPAR alpha seems to play regulatory roles towards Wnt5a/Frizzled2.
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