Ethanol Attenuates Histiotrophic Nutrition Pathways and Alters the Intracellular Redox Environment and Thiol Proteome during Rat Organogenesis
| Autor: | Matthew S. Reed, Karilyn E. Sant, Jason M. Hansen, Jan Pohl, Joseph L. Jilek, Katherine H Cho, Craig Harris |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Proteome Organogenesis Biology Toxicology Endocytosis Fetal Development Rats Sprague-Dawley chemistry.chemical_compound Fetus Pregnancy medicine Animals Conceptus Cysteine Sulfhydryl Compounds Yolk sac Cytoskeleton Ethanol Glutathione Ethanol Disrupts Redox Balance During Organogenesis Cubilin Rats Cell biology medicine.anatomical_structure chemistry Biochemistry Female Oxidation-Reduction Metabolic Networks and Pathways Intracellular |
| Zdroj: | Toxicological Sciences. 147:475-489 |
| ISSN: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/kfv145 |
| Popis: | Ethanol (EtOH) is a reactive oxygen-generating teratogen involved in the etiology of structural and functional developmental defects. Embryonic nutrition, redox environment, and changes in the thiol proteome following EtOH exposures (1.56.0 mg/ml) were studied in rat whole embryo culture. Glutathione (GSH) and cysteine (Cys) concentrations with their respective intracellular redox potentials (Eh) were determined using high-performance liquid chromatography. EtOH reduced GSH and Cys concentrations in embryo (EMB) and visceral yolk sac (VYS) tissues, and also in yolk sac and amniotic fluids. These changes produced greater oxidation as indicated by increasingly positive Eh values. EtOH reduced histiotrophic nutrition pathway activities as measured by the clearance of fluorescin isothiocyanate (FITC)-albumin from culture media. A significant decrease in total FITC clearance was observed at all concentrations, reaching approximately 50% at the highest dose. EtOH-induced changes to the thiol proteome were measured in EMBs and VYSs using isotope-coded affinity tags. Decreased concentrations for specific proteins from cytoskeletal dynamics and endocytosis pathways (α-actinin, α-tubulin, cubilin, and actin-related protein 2); nuclear translocation (Ran and RanBP1); and maintenance of receptor-mediated endocytosis (cubilin) were observed. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis also identified a decrease in ribosomal proteins in both EMB and VYS. Results show that EtOH interferes with nutrient uptake to reduce availability of amino acids and micronutrients required by the conceptus. Intracellular antioxidants such as GSH and Cys are depleted following EtOH and Eh values increase. Thiol proteome analysis in the EMB and VYS show selectively altered actin/cytoskeleton, endocytosis, ribosome biogenesis and function, nuclear transport, and stress-related responses. |
| Databáze: | OpenAIRE |
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