dc.creator | Ramírez-Ponce, M. Pilar | es |
dc.creator | Flores Cordero, Juan Antonio | es |
dc.creator | Barrella, Lorenzo | es |
dc.creator | Alés González de la Higuera, Eva María | es |
dc.date.accessioned | 2023-10-05T14:06:49Z | |
dc.date.available | 2023-10-05T14:06:49Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Ramírez-Ponce, M.P., Flores Cordero, J.A., Barrella, L. y Alés González de la Higuera, E.M. (2023). Ketotifen is a microglial stabilizer by inhibiting secretory vesicle acidification. LIFE SCIENCES, 319. https://doi.org/10.1016/j.lfs.2023.121537. | |
dc.identifier.issn | 0024-3205 | es |
dc.identifier.uri | https://hdl.handle.net/11441/149455 | |
dc.description.abstract | Aims: Microglia survey the brain environment by sensing alarm signals to provide the first line of defense against
injury or infection after which they acquire an activated phenotype, but they also respond to chemical signals
sent from brain mast cells, sentinels of the immune system, when these are degranulated in response to noxious
agents. Nevertheless, excessive microglia activation damages the surrounding healthy neural tissue causing
progressive loss of neurons and inducing chronic inflammation. Thus, it would be of intense interest the
development and application of agents which prevent mast cell mediator release and inhibit the actions of such
mediators once released on microglia.
Main methods: Fluorescence measurements of fura-2 and quinacrine were used to measure intracellular Ca2+
signaling and exocytotic vesicle fusion in resting and activated microglia.
Key findings: We show that treatment of microglia with a cocktail of mast cell mediators induces microglia
activation, phagocytosis, and exocytosis, and reveal by the first-time microglia undergo a phase of vesicular
acidification just before the exocytotic fusion occurs. This acidification is an important process for vesicular
maturation and contributes with ~25 % to the content that the vesicle can store and later release by exocytosis.
Pre-incubation with ketotifen, a mast cell stabilizer and H1R antagonist completely abolished histaminemediated calcium signaling and acidification of microglial organelles, and concomitantly reduced the
discharge of vesicle contents.
Significance: These results highlight a key role for vesicle acidification in microglial physiology and provide a
potential therapeutic target for diseases related to mast cell and microglia-mediated neuroinflammation. | es |
dc.format | application/pdf | es |
dc.format.extent | 11 p. | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | LIFE SCIENCES, 319. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Microglia | es |
dc.subject | Acidification | es |
dc.subject | Calcium signaling | es |
dc.subject | Exocytosis | es |
dc.subject | Ketotifen | es |
dc.subject | Secretory vesicles | es |
dc.subject | Neuroinflammation | es |
dc.title | Ketotifen is a microglial stabilizer by inhibiting secretory vesicle acidification | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología | es |
dc.relation.projectID | BIO-236 | es |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S0024320523001716?via%3Dihub | es |
dc.identifier.doi | 10.1016/j.lfs.2023.121537 | es |
dc.journaltitle | LIFE SCIENCES | es |
dc.publication.volumen | 319 | es |
dc.contributor.funder | Junta de Andalucía | es |