Disruption of the mouse liver epitranscriptome by long-term aroclor 1260 exposure.

Autor: Piell KM; Department of Biochemistry & Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40292, USA., Petri BJ; Department of Biochemistry & Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40292, USA., Head KZ; University of Louisville Hepatobiology and Toxicology Center, USA., Wahlang B; University of Louisville Hepatobiology and Toxicology Center, USA., Xu R; University of Louisville Hepatobiology and Toxicology Center, USA; Department of Chemistry, University of Louisville College of Arts and Sciences, USA., Zhang X; University of Louisville Hepatobiology and Toxicology Center, USA; Department of Chemistry, University of Louisville College of Arts and Sciences, USA; University of Louisville Center for Integrative Environmental Health Sciences (CIEHS), USA., Pan J; Division of Biostatistics and Bioinformatics, Department of Environmental and Public Health Sciences, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA; Cancer Data Science Center, Biostatistics and Informatics Shared Resource, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA., Rai SN; Division of Biostatistics and Bioinformatics, Department of Environmental and Public Health Sciences, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA; Cancer Data Science Center, Biostatistics and Informatics Shared Resource, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA., de Silva K; KY INBRE Bioinformatics Core, University of Louisville, Louisville, KY 40292, USA; Department of Neuroscience Training, University of Louisville, Louisville, KY 40292, USA., Chariker JH; KY INBRE Bioinformatics Core, University of Louisville, Louisville, KY 40292, USA; Department of Neuroscience Training, University of Louisville, Louisville, KY 40292, USA., Rouchka EC; Department of Biochemistry & Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40292, USA; KY INBRE Bioinformatics Core, University of Louisville, Louisville, KY 40292, USA., Tan M; Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA., Li Y; Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA., Cave MC; University of Louisville Hepatobiology and Toxicology Center, USA; University of Louisville Center for Integrative Environmental Health Sciences (CIEHS), USA; Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA; The University of Louisville Superfund Research Center, USA., Klinge CM; Department of Biochemistry & Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40292, USA; University of Louisville Center for Integrative Environmental Health Sciences (CIEHS), USA. Electronic address: carolyn.klinge@louisville.edu.
Jazyk: angličtina
Zdroj: Environmental toxicology and pharmacology [Environ Toxicol Pharmacol] 2023 Jun; Vol. 100, pp. 104138. Date of Electronic Publication: 2023 May 01.
DOI: 10.1016/j.etap.2023.104138
Abstrakt: Chronic environmental exposure to polychlorinated biphenyls (PCBs) is associated with non-alcoholic fatty liver disease (NAFLD) and exacerbated by a high fat diet (HFD). Here, chronic (34 wks.) exposure of low fat diet (LFD)-fed male mice to Aroclor 1260 (Ar1260), a non-dioxin-like (NDL) mixture of PCBs, resulted in steatohepatitis and NAFLD. Twelve hepatic RNA modifications were altered with Ar1260 exposure including reduced abundance of 2'-O-methyladenosine (Am) and N(6)-methyladenosine (m6A), in contrast to increased Am in the livers of HFD-fed, Ar1260-exposed mice reported previously. Differences in 13 RNA modifications between LFD- and HFD- fed mice, suggest that diet regulates the liver epitranscriptome. Integrated network analysis of epitranscriptomic modifications identified a NRF2 (Nfe2l2) pathway in the chronic, LFD, Ar1260-exposed livers and an NFATC4 (Nfatc4) pathway for LFD- vs. HFD-fed mice. Changes in protein abundance were validated. The results demonstrate that diet and Ar1260 exposure alter the liver epitranscriptome in pathways associated with NAFLD.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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