Neuronal Metabolism and Neuroprotection: Neuroprotective Effect of Fingolimod on Menadione-Induced Mitochondrial Damage
| Autor: | Nadia Valverde, Silvana-Yanina Romero-Zerbo, Silvia Claros, José Pavia, María García-Fernández, Federica Boraldi, Estrella Lara, Elisa Martín-Montañez, Antonio Gil, Oscar Fernández |
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| Přispěvatelé: | [Gil,A, Martín-Montañez,E, Fernández,O, Pavia,J] Department of Pharmacology and Pediatrics, Faculty of Medicine, Malaga University, Malaga, Spain. [Martín-Montañez,E, Valverde,N, Lara,E, Claros,S, Pavia,J, Garcia-Fernandez,M] Neuroscience Unit, Biomedical Research Institute of Malaga (IBIMA), Malaga University Hospital, Malaga, Spain. [Valverde,N, Romero-Zerbo,SY, Garcia-Fernandez,M] Department of Human Physiology, Faculty of Medicine, Malaga University, Malaga, Spain. [Boraldi,F] Department of Life Sciences, University of Modena e Reggio Emilia, Modena, Italy., This research was supported by the following projects: PS13/14: Study of the non immunological mechanisms of action of Gilenya (Fingolimod) as therapeutic tool in Multiple Sclerosis and/or other neurodegenerative diseases, Novartis Farmacéutica S.A., CTS507 and CTS156 from Consejería de Economía Innovación Ciencia y Empresa, Junta de Andalucía. N. Valverde was supported by Proyectos I+D+I-Programa Operativo FEDER Andalucía 2014-2020 (UMA18-FEDERJA 004) Junta de Andalucía and Fondo Social Europeo (EU). |
| Rok vydání: | 2020 |
| Předmět: |
Antioxidant
Receptores de esfingosina-1-fosfato mitochondrial damage medicine.medical_treatment Pharmacology Antioxidants Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Antioxidants [Medical Subject Headings] chemistry.chemical_compound Mice Anatomy::Cells::Cells Cultured::Cell Line [Medical Subject Headings] Menadione Organisms::Eukaryota::Animals [Medical Subject Headings] Homeostasis Glycolysis Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative Stress [Medical Subject Headings] lcsh:QH301-705.5 Anatomy::Nervous System::Neurons [Medical Subject Headings] Mitocondrias Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Mitochondria [Medical Subject Headings] Phenomena and Processes::Metabolic Phenomena::Metabolism::Carbohydrate Metabolism::Glycolysis [Medical Subject Headings] Neurons Chemistry Neuroprotección Vitamin K 3 Neurodegenerative Diseases General Medicine Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons Cyclic::Hydrocarbons Aromatic::Polycyclic Hydrocarbons Aromatic::Naphthalenes::Naphthoquinones::Vitamin K::Vitamin K 3 [Medical Subject Headings] Fingolimod Neuroprotection Mitochondria Neuroprotective Agents medicine.drug sphingosine-1-phosphate receptor analogue fingolimod phosphate neuroprotection glycolytic pathway pentose phosphate pathway redox homeostasis Oxidative phosphorylation Pentose phosphate pathway Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Protective Agents::Neuroprotective Agents [Medical Subject Headings] Article Cell Line Oxidación-reducción Vía de la pentosa-fosfato Diseases::Nervous System Diseases::Neurodegenerative Diseases [Medical Subject Headings] medicine Animals Sphingosine-1-Phosphate Receptors Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] Protein nitrosylation Fingolimod Hydrochloride Glucólisis Oxidative Stress lcsh:Biology (General) |
| Zdroj: | Cells Cells; Volume 10; Issue 1; Pages: 34 Cells, Vol 10, Iss 34, p 34 (2021) |
| ISSN: | 2073-4409 |
| Popis: | Imbalance in the oxidative status in neurons, along with mitochondrial damage, are common characteristics in some neurodegenerative diseases. The maintenance in energy production is crucial to face and recover from oxidative damage, and the preservation of different sources of energy production is essential to preserve neuronal function. Fingolimod phosphate is a drug with neuroprotective and antioxidant actions, used in the treatment of multiple sclerosis. This work was performed in a model of oxidative damage on neuronal cell cultures exposed to menadione in the presence or absence of fingolimod phosphate. We studied the mitochondrial function, antioxidant enzymes, protein nitrosylation, and several pathways related with glucose metabolism and glycolytic and pentose phosphate in neuronal cells cultures. Our results showed that menadione produces a decrease in mitochondrial function, an imbalance in antioxidant enzymes, and an increase in nitrosylated proteins with a decrease in glycolysis and glucose-6-phosphate dehydrogenase. All these effects were counteracted when fingolimod phosphate was present in the incubation media. These effects were mediated, at least in part, by the interaction of this drug with its specific S1P receptors. These actions would make this drug a potential tool in the treatment of neurodegenerative processes, either to slow progression or alleviate symptoms. |
| Databáze: | OpenAIRE |
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