Characterization of macrophage phenotype, redox, and purinergic response upon chronic treatment with methionine and methionine sulfoxide in mice
| Autor: | Natália Pontes Bona, Thaís S Franceschi, Francieli Moro Stefanello, Carlus Augustu Tavares do Couto, Carmen Regla Vargas, Elizandra Braganhol, Luiza Spohr, Mayara Sandrielly Pereira Soares, Fernanda Cardoso Teixeira, Roselia Maria Spanevello, Marion Deon, Nathalia Stark Pedra |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Clinical Biochemistry Macrophage polarization Glycine N-Methyltransferase Pharmacology medicine.disease_cause Biochemistry Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound Mice Methionine medicine Animals Amino Acid Metabolism Inborn Errors chemistry.chemical_classification Glutathione Peroxidase 030102 biochemistry & molecular biology biology Chemistry Methionine sulfoxide Superoxide Dismutase Glutathione peroxidase Macrophages Organic Chemistry Purinergic receptor Cell Polarity medicine.disease Catalase Oxidative Stress 030104 developmental biology Phenotype biology.protein Hypermethioninemia Oxidation-Reduction Oxidative stress |
| Zdroj: | Amino acids. 52(4) |
| ISSN: | 1438-2199 |
| Popis: | Hypermethioninemia is a disorder characterized by high plasma levels of methionine (Met) and its metabolites such as methionine sulfoxide (MetO). Studies have reported associated inflammatory complications, but the mechanisms involved in the pathophysiology of hypermethioninemia are still uncertain. The present study aims to evaluate the effect of chronic administration of Met and/or MetO on phenotypic characteristics of macrophages, in addition to oxidative stress, purinergic system, and inflammatory mediators in macrophages. In this study, Swiss male mice were subcutaneously injected with Met and MetO at concentrations of 0.35–1.2 g/kg body weight and 0.09–0.3 g/kg body weight, respectively, from the 10th–38th day post-birth, while the control group was treated with saline solution. The results revealed that Met and/or MetO induce an M1/classical activation phenotype associated with increased levels of tumor necrosis factor alpha and nitrite, and reduced arginase activity. It was also found that Met and/or MetO alter the activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, as well as the levels of thiol and reactive oxygen species in macrophages. The chronic administration of Met and/or MetO also promotes alteration in the hydrolysis of ATP and ADP, as indicated by the increased activity of ectonucleotidases. These results demonstrate that chronic administration of Met and/or MetO promotes activated pro-inflammatory profile by inducing M1/classical macrophage polarization. Thus, the changes in redox status and purinergic system upon chronic Met and/or MetO exposure may contribute towards better understanding of the alterations consistent with hypermethioninemic patients. |
| Databáze: | OpenAIRE |
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