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LPS-Activated Microglial Cell-Derived Conditioned Medium Protects HT22 Neuronal Cells against Glutamate-Induced Ferroptosis
Neuron-glia interactions are essential for the central nervous system’s homeostasis. Microglial cells are one of the key support cells in the brain that respond to disruptions in such homeostasis. Although their participation in neuroinflammation is well known, studies investigating their role in fe...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917809/ https://www.ncbi.nlm.nih.gov/pubmed/36769233 http://dx.doi.org/10.3390/ijms24032910 |
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author | Jacques, Mauricio Tavares Saso, Luciano Farina, Marcelo |
author_facet | Jacques, Mauricio Tavares Saso, Luciano Farina, Marcelo |
author_sort | Jacques, Mauricio Tavares |
collection | PubMed |
description | Neuron-glia interactions are essential for the central nervous system’s homeostasis. Microglial cells are one of the key support cells in the brain that respond to disruptions in such homeostasis. Although their participation in neuroinflammation is well known, studies investigating their role in ferroptosis, an iron-dependent form of nonapoptotic cell death, are lacking. To address this issue, we explored whether microglial (BV-2 cells) activation products can intensify, mitigate or block oxidative and/or ferroptotic damage in neuronal cells (HT22 cell line). Cultured BV-2 microglial cells were stimulated with 5–100 ng/mL lipopolysaccharide (LPS) for 24 h and, after confirmation of microglial activation, their culture medium (conditioned media; CM) was transferred to neuronal cells, which was subsequently (6 h later) exposed to glutamate or tert-butyl hydroperoxide (t-BuOOH). As a major finding, HT22 cells pretreated for 6 h with CM exhibited a significant ferroptosis-resistant phenotype characterized by decreased sensitivity to glutamate (15 mM)-induced cytotoxicity. However, no significant protective effects of LPS-activated microglial cell-derived CM were observed in t-BuOOH (30 µM)-challenged cells. In summary, activated microglia-derived molecules may protect neuronal cells against ferroptosis. The phenomenon observed in this work highlights the beneficial relationship between microglia and neurons, highlighting new possibilities for the control of ferroptosis. |
format | Online Article Text |
id | pubmed-9917809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99178092023-02-11 LPS-Activated Microglial Cell-Derived Conditioned Medium Protects HT22 Neuronal Cells against Glutamate-Induced Ferroptosis Jacques, Mauricio Tavares Saso, Luciano Farina, Marcelo Int J Mol Sci Article Neuron-glia interactions are essential for the central nervous system’s homeostasis. Microglial cells are one of the key support cells in the brain that respond to disruptions in such homeostasis. Although their participation in neuroinflammation is well known, studies investigating their role in ferroptosis, an iron-dependent form of nonapoptotic cell death, are lacking. To address this issue, we explored whether microglial (BV-2 cells) activation products can intensify, mitigate or block oxidative and/or ferroptotic damage in neuronal cells (HT22 cell line). Cultured BV-2 microglial cells were stimulated with 5–100 ng/mL lipopolysaccharide (LPS) for 24 h and, after confirmation of microglial activation, their culture medium (conditioned media; CM) was transferred to neuronal cells, which was subsequently (6 h later) exposed to glutamate or tert-butyl hydroperoxide (t-BuOOH). As a major finding, HT22 cells pretreated for 6 h with CM exhibited a significant ferroptosis-resistant phenotype characterized by decreased sensitivity to glutamate (15 mM)-induced cytotoxicity. However, no significant protective effects of LPS-activated microglial cell-derived CM were observed in t-BuOOH (30 µM)-challenged cells. In summary, activated microglia-derived molecules may protect neuronal cells against ferroptosis. The phenomenon observed in this work highlights the beneficial relationship between microglia and neurons, highlighting new possibilities for the control of ferroptosis. MDPI 2023-02-02 /pmc/articles/PMC9917809/ /pubmed/36769233 http://dx.doi.org/10.3390/ijms24032910 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jacques, Mauricio Tavares Saso, Luciano Farina, Marcelo LPS-Activated Microglial Cell-Derived Conditioned Medium Protects HT22 Neuronal Cells against Glutamate-Induced Ferroptosis |
title | LPS-Activated Microglial Cell-Derived Conditioned Medium Protects HT22 Neuronal Cells against Glutamate-Induced Ferroptosis |
title_full | LPS-Activated Microglial Cell-Derived Conditioned Medium Protects HT22 Neuronal Cells against Glutamate-Induced Ferroptosis |
title_fullStr | LPS-Activated Microglial Cell-Derived Conditioned Medium Protects HT22 Neuronal Cells against Glutamate-Induced Ferroptosis |
title_full_unstemmed | LPS-Activated Microglial Cell-Derived Conditioned Medium Protects HT22 Neuronal Cells against Glutamate-Induced Ferroptosis |
title_short | LPS-Activated Microglial Cell-Derived Conditioned Medium Protects HT22 Neuronal Cells against Glutamate-Induced Ferroptosis |
title_sort | lps-activated microglial cell-derived conditioned medium protects ht22 neuronal cells against glutamate-induced ferroptosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917809/ https://www.ncbi.nlm.nih.gov/pubmed/36769233 http://dx.doi.org/10.3390/ijms24032910 |
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