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Carbon monoxide (CO) is a novel inhibitor of connexin hemichannels

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dc.contributor.author León-Paravic, Carmen
dc.contributor.author Figueroa, Vania
dc.contributor.author Guzmán, Diego
dc.contributor.author Valderrama, Carlos
dc.contributor.author Vallejos, Antonio
dc.contributor.author Fiori, Mariana
dc.contributor.author Altenberg, Guillermo
dc.contributor.author Reuss, Luis
dc.contributor.author Retamal, Mauricio
dc.date.accessioned 2017-03-07T15:22:36Z
dc.date.available 2017-03-07T15:22:36Z
dc.date.issued 2014
dc.identifier.citation J Biol Chem. 2014 Dec 26;289(52):36150-7 es_CL
dc.identifier.uri http://dx.doi.org/10.1074/jbc.M114.602243 es_CL
dc.identifier.uri http://hdl.handle.net/11447/1007
dc.description Centro de Fisiología Celular e Integrativa es_CL
dc.description.abstract Hemichannels (HCs) are hexamers of connexins that can form gap-junction channels at points of cell contacts or "free HCs" at non-contacting regions. HCs are involved in paracrine and autocrine cell signaling, and under pathological conditions may induce and/or accelerate cell death. Therefore, studies of HC regulation are of great significance. Nitric oxide affects the activity of Cx43 and Cx46 HCs, whereas carbon monoxide (CO), another gaseous transmitter, modulates the activity of several ion channels, but its effect on HCs has not been explored. We studied the effect of CO donors (CORMs) on Cx46 HCs expressed in Xenopus laevis oocytes using two-electrode voltage clamp and on Cx43 and Cx46 expressed in HeLa cells using a dye-uptake technique. CORM-2 inhibited Cx46 HC currents in a concentration-dependent manner. The C-terminal domain and intracellular Cys were not necessary for the inhibition. The effect of CORM-2 was not prevented by guanylyl-cyclase, protein kinase G, or thioredoxin inhibitors, and was not due to endocytosis of HCs. However, the effect of CORM-2 was reversed by reducing agents that act extracellularly. Additionally, CO inhibited dye uptake of HeLa cells expressing Cx43 or Cx46, and MCF-7 cells, which endogenously express Cx43 and Cx46. Because CORM-2 carbonylates Cx46 in vitro and induces conformational changes, a direct effect of that CO on Cx46 is possible. The inhibition of HCs could help to understand some of the biological actions of CO in physiological and pathological conditions. es_CL
dc.format.extent 8 es_CL
dc.language.iso en_US es_CL
dc.publisher The American Society for Biochemistry and Molecular Biology es_CL
dc.subject Carbon Monoxide es_CL
dc.subject Carbonylation es_CL
dc.subject Connexin es_CL
dc.subject Hemichannels es_CL
dc.subject Ion Channel es_CL
dc.subject Post-translational Modification (PTM) es_CL
dc.subject Redox Signaling es_CL
dc.title Carbon monoxide (CO) is a novel inhibitor of connexin hemichannels es_CL
dc.type Artículo es_CL


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