Pannexin-1 couples to maitotoxin and nigericin- induced il-1β release through a dye-uptake independent pathway

Pelegrin, Pablo; Surprenant, Annmarie

Publication:
Pannexin-1 couples to maitotoxin and nigericin- induced il-1β release through a dye-uptake independent pathway

dc.contributor.author	Pelegrin, Pablo
dc.contributor.author	Surprenant, Annmarie
dc.contributor.department	Bioquímica y Biología Molecular B e Inmunología
dc.date.accessioned	2024-01-25T09:24:38Z
dc.date.available	2024-01-25T09:24:38Z
dc.date.issued	2007
dc.description	©2007. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepte version of a Published Work that appeared in final form in Journal of Biological Chemistry. To access the final edited and published work see https://doi.org/10.1074/jbc.M610351200	es
dc.description.abstract	Pannexin-1 is a recently identified membrane protein that can act as a non-selective pore permeable to dyes such as ethidium when ectopically expressed. Blockade of pannexin-1 in macrophage endogenously expressing the ATP-gated P2X7 receptor (P2X7R) blocks the initial dye uptake, but not the ionic current, and also blocks processing and release of interleukin-1β (IL-1β) in response to P2X7R activation. These results suggest that pannexin-1 may be a hemichannel activated by the P2X7R to provide the conduit for dye uptake and downstream signalling to processing and release of IL-1β. We have pursued this hypothesis by measuring dye uptake and IL-1β processing and release in mouse J774 macrophage in response to P2X7R activation and to maitotoxin and nigericin, two agents considered to evoke IL-1β release via the same mechanism. Experiments were carried out over time periods during which no LDH was released from cells in order to examine only non-cytolytic pathways. P2X7R activation evoked dye-uptake that could be separated into two components by pannexin-1 inhibition: an initial rapid phase and a slower pannexin-1- independent phase. Maitotoxin evoked dye uptake was unaltered by pannexin-1 inhibition. Nigericin did not induce dye uptake. Inhibition of pannexin-1 blocked caspase-1 and IL-1β processing and release in response to all three stimuli. Thus, while pannexin-1 is required for IL-1β release in response to maitotoxin, nigericin and ATP, a mechanism distinct from pannexin-1 hemichannel activation must underlie the former two processes.	es
dc.format	application/pdf	es
dc.format.extent	21	es
dc.identifier.citation	Journal of Biological Chemistry, volumen 282, nº 4, año 2007, páginas 2386-2394
dc.identifier.doi	10.1074/jbc.M610351200
dc.identifier.issn	1083-351X
dc.identifier.issn	0021-9258
dc.identifier.uri	http://hdl.handle.net/10201/137733
dc.language	eng	es
dc.publisher	Elsevier	es
dc.relation	Wellcome Trust y AstraZeneca Charnwood UK	es
dc.relation.publisherversion	https://www.jbc.org/article/S0021-9258(20)72108-3/fulltext	es
dc.rights	info:eu-repo/semantics/openAccess	es
dc.rights	Attribution-NonCommercial-NoDerivatives 4.0 Internacional	*
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/	*
dc.subject	Panexina	es
dc.subject	Citocinas	es
dc.subject	Macrófagos	es
dc.subject.other	CDU::6 - Ciencias aplicadas	es
dc.title	Pannexin-1 couples to maitotoxin and nigericin- induced il-1β release through a dye-uptake independent pathway	es
dc.type	info:eu-repo/semantics/article	es
dspace.entity.type	Publication	es