Distinct UPR and Autophagic Functions Define Cell-Specific Responses to Proteotoxic Stress in Microglial and Neuronal Cell Lines
first_pagesettingsOrder Article Reprints Open AccessArticle Distinct UPR and Autophagic Functions Define Cell-Specific Responses to Proteotoxic Stress in Microglial and Neuronal Cell Lines by Helena Domínguez-Martín 1,2,†,Elena Gavilán 1,2,†ORCID,Celia Parrado 1,Miguel A. Burguillos 1,2ORCID,Paula D...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/168710 |
| Acceso en línea: | https://hdl.handle.net/11441/168710 https://doi.org/10.3390/cells13242069 |
| Access Level: | acceso abierto |
| Palabra clave: | proteotoxic stress autophagy proteasome microglia neurons phagocytosis proteostasis |
| Sumario: | first_pagesettingsOrder Article Reprints Open AccessArticle Distinct UPR and Autophagic Functions Define Cell-Specific Responses to Proteotoxic Stress in Microglial and Neuronal Cell Lines by Helena Domínguez-Martín 1,2,†,Elena Gavilán 1,2,†ORCID,Celia Parrado 1,Miguel A. Burguillos 1,2ORCID,Paula Daza 3 andDiego Ruano 1,2,* 1 Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla (US), 41012 Sevilla, Spain 2 Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Sevilla (US), 41013 Sevilla, Spain 3 Departamento de Biología Celular, Facultad de Biología, Universidad de Sevilla (US), 41012 Sevilla, Spain * Author to whom correspondence should be addressed. † These authors contributed equally to this work and share first authorship. Cells 2024, 13(24), 2069; https://doi.org/10.3390/cells13242069 Submission received: 4 November 2024 / Revised: 10 December 2024 / Accepted: 13 December 2024 / Published: 15 December 2024 (This article belongs to the Special Issue Understanding the Interplay Between Autophagy and Neurodegeneration) Downloadkeyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract Autophagy is a catabolic process involved in different cellular functions. However, the molecular pathways governing its potential roles in different cell types remain poorly understood. We investigated the role of autophagy in the context of proteotoxic stress in two central nervous system cell types: the microglia-like cell line BV2 and the neuronal-like cell line N2a. Proteotoxic stress, induced by proteasome inhibition, produced early apoptosis in BV2 cells, due in part to a predominant activation of the PERK-CHOP pathway. In contrast, N2a cells showcased greater resistance and robust induction of the IRE1α-sXbp1 arm of the UPR. We also demonstrated that proteotoxic stress activated autophagy in both cell lines but with different kinetics and cellular functions. In N2a cells, autophagy restored cellular proteostasis, while in BV2 cells, it participated in regulating phagocytosis. Finally, proteotoxic stress predominantly activated the mTORC2-AKT-FOXO1-β-catenin pathway in BV2 cells, while N2a cells preferentially induced the PDK1-AKT-FOXO3 axis. Collectively, our findings suggest that proteotoxic stress triggers cell-specific responses in microglia and neurons, with different physiological outcomes. |
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