Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity
Microglial-neuronal interactions are essential for brain physiopathology. In this framework, recent data have changed the concept of microglia from essentially macrophagic cells to crucial elements in maintaining neuronal homeostasis and function through the release of neuroprotective molecules. Usi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2012-05-01
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| Series: | Neurosignals |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/337115 |
| _version_ | 1811210592685391872 |
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| author | Elisabetta Polazzi Ilaria Mengoni Marco Caprini Emiliano Peña-Altamira Ewelina Kurtys Barbara Monti |
| author_facet | Elisabetta Polazzi Ilaria Mengoni Marco Caprini Emiliano Peña-Altamira Ewelina Kurtys Barbara Monti |
| author_sort | Elisabetta Polazzi |
| collection | DOAJ |
| description | Microglial-neuronal interactions are essential for brain physiopathology. In this framework, recent data have changed the concept of microglia from essentially macrophagic cells to crucial elements in maintaining neuronal homeostasis and function through the release of neuroprotective molecules. Using proteomic analysis, here we identify copper-zinc superoxide dismutase (SOD1) as a protein produced and released by cultured rat primary microglia. Evidence for a neuroprotective role of microglia-derived SOD1 resulted from experiments in which primary cerebellar granule neurons (CGNs) were exposed to the dopaminergic toxin 6-hydroxydopamine (6-OHDA). Microglial conditioned medium, in which SOD1 had accumulated, protected CGNs from degeneration, and neuroprotection was abrogated by SOD1 inhibitors. These effects were replicated when exogenous SOD1 was added to a nonconditioned medium. SOD1 neuroprotective action was mediated by increased cell calcium from an external source. Further experiments demonstrated the specificity of SOD1 neuroprotection against 6-OHDA compared to other types of neurotoxic challenges. SOD1, constitutively produced and released by microglia through a lysosomal secretory pathway, is identified here for the first time as an essential component of neuroprotection mediated by microglia. This novel information is relevant to stimulating further studies of microglia-mediated neuroprotection in in vivo models of neurodegenerative diseases. |
| first_indexed | 2024-04-12T04:58:34Z |
| format | Article |
| id | doaj.art-cf8e13a9801a4370857413c015b2a71f |
| institution | Directory Open Access Journal |
| issn | 1424-862X 1424-8638 |
| language | English |
| last_indexed | 2024-04-12T04:58:34Z |
| publishDate | 2012-05-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Neurosignals |
| spelling | doaj.art-cf8e13a9801a4370857413c015b2a71f2022-12-22T03:47:03ZengCell Physiol Biochem Press GmbH & Co KGNeurosignals1424-862X1424-86382012-05-01211-211212810.1159/000337115337115Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA NeurotoxicityElisabetta PolazziIlaria MengoniMarco CapriniEmiliano Peña-AltamiraEwelina KurtysBarbara MontiMicroglial-neuronal interactions are essential for brain physiopathology. In this framework, recent data have changed the concept of microglia from essentially macrophagic cells to crucial elements in maintaining neuronal homeostasis and function through the release of neuroprotective molecules. Using proteomic analysis, here we identify copper-zinc superoxide dismutase (SOD1) as a protein produced and released by cultured rat primary microglia. Evidence for a neuroprotective role of microglia-derived SOD1 resulted from experiments in which primary cerebellar granule neurons (CGNs) were exposed to the dopaminergic toxin 6-hydroxydopamine (6-OHDA). Microglial conditioned medium, in which SOD1 had accumulated, protected CGNs from degeneration, and neuroprotection was abrogated by SOD1 inhibitors. These effects were replicated when exogenous SOD1 was added to a nonconditioned medium. SOD1 neuroprotective action was mediated by increased cell calcium from an external source. Further experiments demonstrated the specificity of SOD1 neuroprotection against 6-OHDA compared to other types of neurotoxic challenges. SOD1, constitutively produced and released by microglia through a lysosomal secretory pathway, is identified here for the first time as an essential component of neuroprotection mediated by microglia. This novel information is relevant to stimulating further studies of microglia-mediated neuroprotection in in vivo models of neurodegenerative diseases.http://www.karger.com/Article/FullText/337115Conditioned mediumSOD1 NeuroprotectionCerebellar granule neurons6-HydroxydopamineMicroglia |
| spellingShingle | Elisabetta Polazzi Ilaria Mengoni Marco Caprini Emiliano Peña-Altamira Ewelina Kurtys Barbara Monti Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity Neurosignals Conditioned medium SOD1 Neuroprotection Cerebellar granule neurons 6-Hydroxydopamine Microglia |
| title | Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity |
| title_full | Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity |
| title_fullStr | Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity |
| title_full_unstemmed | Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity |
| title_short | Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity |
| title_sort | copper zinc superoxide dismutase sod1 is released by microglial cells and confers neuroprotection against 6 ohda neurotoxicity |
| topic | Conditioned medium SOD1 Neuroprotection Cerebellar granule neurons 6-Hydroxydopamine Microglia |
| url | http://www.karger.com/Article/FullText/337115 |
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