Selenium induces cholinergic motor neuron degeneration in Caenorhabditis elegans
| Autor: | Nathaniel J. Szewczyk, Miguel Estevez, Kathleen L. Morgan, Antonio Miranda-Vizuete, Luke Teece, Annette O. Estevez, Catherine L. Mueller |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Antioxidant
medicine.medical_treatment Movement Vesicular Acetylcholine Transport Proteins Green Fluorescent Proteins Muscle Proteins Cell Count Toxicology medicine.disease_cause Antioxidants Article Animals Genetically Modified Selenium Adjuvants Immunologic Vesicular acetylcholine transporter medicine Animals Paralysis Receptors Cholinergic Cholinergic neuron Caenorhabditis elegans Caenorhabditis elegans Proteins Acetylcholine receptor Motor Neurons Analysis of Variance biology Dose-Response Relationship Drug General Neuroscience Muscles Reproduction Neurodegeneration food and beverages Galactosides medicine.disease biology.organism_classification Glutathione Actins Cholinergic Neurons Cell biology Biochemistry Levamisole Mutation Nerve Degeneration Cholinergic Oxidative stress Signal Transduction |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Selenium is an essential micronutrient required for cellular antioxidant systems, yet at higher doses it induces oxidative stress. Additionally, in vertebrates environmental exposures to toxic levels of selenium can cause paralysis and death. Here we show that selenium-induced oxidative stress leads to decreased cholinergic signaling and degeneration of cholinergic neurons required for movement and egg-laying in Caenorhabditis elegans. Exposure to high levels of selenium leads to proteolysis of a soluble muscle protein through mechanisms suppressible by two pharmacological agents, levamisole and aldicarb which enhance cholinergic signaling in muscle. In addition, animals with reduction-of-function mutations in genes encoding post-synaptic levamisole-sensitive acetylcholine receptor subunits or the vesicular acetylcholine transporter developed impaired forward movement faster during selenium-exposure than normal animals, again confirming that selenium reduces cholinergic signaling. Finally, the antioxidant reduced glutathione, inhibits selenium-induced reductions in egg-laying through a cellular protective mechanism dependent on the C. elegans glutaredoxin, GLRX-21. These studies provide evidence that the environmental toxicant selenium induces neurodegeneration of cholinergic neurons through depletion of glutathione, a mechanism linked to the neuropathology of Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. This research was supported by grants from the Jim Himelic Foundation (AE and ME), Southern Arizona Foundation (ME), Keatings Institute (ME), National Institutes of Environmental Health Sciences [R21-ES012305 to AE and ME], Arthritis and Musculoskeletal and Skin Diseases [R01-AR054342 to NJS], Instituto de Salud Carlos III [Projects PI050065 and PI080557, co-financed by Fondo Social Europeo, FEDER to AMV] and Junta de Andalucía [Projects CVI-3629 and CVI-2697to AMV]. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources (NCRR). |
| Databáze: | OpenAIRE |
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