P2X7 Receptor Triggers Lysosomal Leakage Through Calcium Mobilization in a Mechanism Dependent on Pannexin-1 Hemichannels

dc.creatorSantos, Stephanie Alexia Cristina Silva
dc.creatorPersechini, Pedro Muanis
dc.creatorSantos, Bianca Monteiro Henriques
dc.creatorSantos, Victória Gabriela Bello
dc.creatorCastro, Newton G.
dc.creatorSousa, Júlia Costa de
dc.creatorGenta, Fernando Ariel
dc.creatorSantiago, Marcelo Felippe
dc.creatorSilva, Robson Coutinho
dc.creatorSavio, Luiz Eduardo Baggio
dc.creatorKurtenbach, Eleonora
dc.date2022-06-23T17:36:44Z
dc.date2022-06-23T17:36:44Z
dc.date2022
dc.date.accessioned2023-09-26T22:39:26Z
dc.date.available2023-09-26T22:39:26Z
dc.identifierSANTOS, Stephanie Alexia Cristina Silva et al. P2X7 Receptor Triggers Lysosomal Leakage Through Calcium Mobilization in a Mechanism Dependent on Pannexin-1 Hemichannels. Frontiers in Immunology, v. 13, Article 752105, p. 1 - 13, Feb. 2022.
dc.identifier1664-3224
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/53451
dc.identifier10.3389/fimmu.2022.752105
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8881565
dc.descriptionThe P2X7 receptor is a critical purinergic receptor in immune cells. Its activation was associated with cathepsin release into macrophage cytosol, suggesting its involvement in lysosomal membrane permeabilization (LMP) and leakage. Nevertheless, the mechanisms by which P2X7 receptor activation induces LMP and leakage are unclear. This study investigated cellular mechanisms associated with endosomal and lysosomal leakage triggered by P2X7 receptor activation. We found that ATP at 500 mM and 5 mM (but not 50 mM) induced LMP in non-stimulated peritoneal macrophages. This effect was not observed in P2X7-deficient or A740003-pretreated macrophages. We found that the P2X7 receptor and pannexin-1 channels mediate calcium influx that might be important for activating specific ion channels (TRPM2 and two-pore channels) on the membranes of late endosomes and lysosomes leading to LMP leakage and consequent cathepsin release. These findings suggest the critical role of the P2X7 receptor in inflammatory and infectious diseases via lysosomal dysfunction.
dc.formatapplication/pdf
dc.languageeng
dc.publisherFrontiers Media
dc.rightsopen access
dc.subjectLisossomos
dc.subjectReceptor P2
dc.subjectCatepsinas
dc.subjectATP extracelular
dc.subjectPermeabilização lisossomal
dc.subjectLysosomes
dc.subjectP2 receptor
dc.subjectCathepsins
dc.subjectExtracellular ATP
dc.subjectLysosomal permeabilization
dc.titleP2X7 Receptor Triggers Lysosomal Leakage Through Calcium Mobilization in a Mechanism Dependent on Pannexin-1 Hemichannels
dc.typeArticle


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