Multiomics Analysis of PCB126's Effect on a Mouse Chronic-Binge Alcohol Feeding Model.

Autor: Gripshover TC; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Louisville, Louisville, Kentucky, USA.; University of Louisville Superfund Research Program, University of Louisville, Louisville, Kentucky, USA., Wahlang B; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Louisville, Louisville, Kentucky, USA.; University of Louisville Superfund Research Program, University of Louisville, Louisville, Kentucky, USA.; The Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, Kentucky, USA., Head KZ; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Louisville, Louisville, Kentucky, USA.; Hepatobiology & Toxicology COBRE, University of Louisville School of Medicine, Louisville, Kentucky, USA., Luo J; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Louisville, Louisville, Kentucky, USA., Bolatimi OE; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA., Smith ML; The Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, Kentucky, USA.; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, Kentucky, USA., Rouchka EC; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Kentucky IDeA Network of Biomedical Research Excellence (KY INBRE) Bioinformatics Core, University of Louisville, Louisville, Kentucky, USA., Chariker JH; Kentucky IDeA Network of Biomedical Research Excellence (KY INBRE) Bioinformatics Core, University of Louisville, Louisville, Kentucky, USA.; Department of Neuroscience Training, University of Louisville, Louisville, Kentucky, USA., Xu J; Department of Pediatrics, Pediatric Research Institute, University of Louisville School of Medicine, Louisville, Kentucky, USA., Cai L; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA.; The Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, Kentucky, USA.; Department of Pediatrics, Pediatric Research Institute, University of Louisville School of Medicine, Louisville, Kentucky, USA., Cummins TD; Division of Nephrology and Hypertension, Department of Medicine and Clinical Proteomics Center, University of Louisville, Louisville, Kentucky, USA., Merchant ML; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA.; The Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, Kentucky, USA.; Division of Nephrology and Hypertension, Department of Medicine and Clinical Proteomics Center, University of Louisville, Louisville, Kentucky, USA.; University of Louisville Alcohol Research Center, University of Louisville, Louisville, Kentucky, USA., Zheng H; The Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, Kentucky, USA., Kong M; The Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, Kentucky, USA.; Department of Bioinformatics and Biostatistics School of Public Health and Information Sciences, University of Louisville, Louisville, Kentucky, USA.; University of Louisville Alcohol Research Center, University of Louisville, Louisville, Kentucky, USA.; Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA., Cave MC; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Louisville, Louisville, Kentucky, USA.; University of Louisville Superfund Research Program, University of Louisville, Louisville, Kentucky, USA.; The Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, Kentucky, USA.; Hepatobiology & Toxicology COBRE, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, Kentucky, USA.; University of Louisville Alcohol Research Center, University of Louisville, Louisville, Kentucky, USA.; The Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky, USA.; The Liver Transplant Program at UofL Health - Jewish Hospital Trager Transplant Center, Louisville, Kentucky, USA.
Jazyk: angličtina
Zdroj: Environmental health perspectives [Environ Health Perspect] 2024 Apr; Vol. 132 (4), pp. 47007. Date of Electronic Publication: 2024 Apr 15.
DOI: 10.1289/EHP14132
Abstrakt: Background: Environmental pollutants, including polychlorinated biphenyls (PCBs) have been implicated in the pathogenesis of liver disease. Our group recently demonstrated that PCB126 promoted steatosis, hepatomegaly, and modulated intermediary metabolism in a rodent model of alcohol-associated liver disease (ALD).
Objective: To better understand how PCB126 promoted ALD in our previous model, the current study adopts multiple omics approaches to elucidate potential mechanistic hypotheses.
Methods: Briefly, male C57BL/6J mice were exposed to 0.2 mg / kg polychlorinated biphenyl (PCB) 126 or corn oil vehicle prior to ethanol (EtOH) or control diet feeding in the chronic-binge alcohol feeding model. Liver tissues were collected and prepared for mRNA sequencing, phosphoproteomics, and inductively coupled plasma mass spectrometry for metals quantification.
Results: Principal component analysis showed that PCB126 uniquely modified the transcriptome in EtOH-fed mice. EtOH feeding alone resulted in > 4,000 differentially expressed genes (DEGs), and PCB126 exposure resulted in more DEGs in the EtOH-fed group (907 DEGs) in comparison with the pair-fed group (503 DEGs). Top 20 significant gene ontology (GO) biological processes included "peptidyl tyrosine modifications," whereas top 25 significantly decreasing GO molecular functions included "metal/ion/zinc binding." Quantitative, label-free phosphoproteomics and western blot analysis revealed no major significant PCB126 effects on total phosphorylated tyrosine residues in EtOH-fed mice. Quantified hepatic essential metal levels were primarily significantly lower in EtOH-fed mice. PCB126-exposed mice had significantly lower magnesium, cobalt, and zinc levels in EtOH-fed mice.
Discussion: Previous work has demonstrated that PCB126 is a modifying factor in metabolic dysfunction-associated steatotic liver disease (MASLD), and our current work suggests that pollutants also modify ALD. PCB126 may, in part, be contributing to the malnutrition aspect of ALD, where metal deficiency is known to contribute and worsen prognosis. https://doi.org/10.1289/EHP14132.
Databáze: MEDLINE
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