Role of Akt and Ca<SUP>2+</SUP> on cell permeabilization via connexin43 hemichannels induced by metabolic inhibition

dc.contributor.authorSalas, Daniela
dc.contributor.authorPuebla, Carlos
dc.contributor.authorLampe, Paul D.
dc.contributor.authorLavandero, Sergio
dc.contributor.authorSaez, Juan C.
dc.date.accessioned2025-01-23T21:36:00Z
dc.date.available2025-01-23T21:36:00Z
dc.date.issued2015
dc.description.abstractConnexin hemichannels are regulated under physiological and pathological conditions. Metabolic inhibition, a model of ischemia, promotes surface hemichannel activation associated, in part, with increased surface hemichannel levels, but little is known about its underlying mechanism. Here, we investigated the role of Akt on the connexin43 hemichannel's response induced by metabolic inhibition. In HeLa cells stably transfected with rat connexin43 fused to EGFP (HeLa43 cells), metabolic inhibition induced a transient Akt activation necessary to increase the amount of surface connexin43. The increase in levels of surface connexin43 was also found to depend on an intracellular Ca2+ signal increase that was partially mediated by Akt activation. However, the metabolic inhibition-induced Akt activation was not significantly affected by intracellular Ca2+ chelation. The Akt-dependent increase in connexin43 hemichannel activity in HeLa43 cells also occurred after oxygen-glucose deprivation, another ischemia-like condition, and in cultured cortical astrocytes (endogenous connexin43 expression system) under metabolic inhibition. Since opening of hemichannels has been shown to accelerate cell death, inhibition of Akt-dependent phosphotylation of connexin43 hemichannels could reduce cell death induced by ischemia/reperfusion. (C) 2015 Elsevier B.V. All rights reserved.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.bbadis.2015.03.004
dc.identifier.eissn0006-3002
dc.identifier.issn0925-4439
dc.identifier.urihttps://doi.org/10.1016/j.bbadis.2015.03.004
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/101555
dc.identifier.wosidWOS:000355715200006
dc.issue.numero7
dc.language.isoen
dc.pagina.final1277
dc.pagina.inicio1268
dc.revistaBiochimica et biophysica acta-molecular basis of disease
dc.rightsacceso restringido
dc.subjectSurface hemichannels
dc.subjectIntracellular Ca2+
dc.subjectOxygen-glucose deprivation
dc.subjectAkt activation
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleRole of Akt and Ca<SUP>2+</SUP> on cell permeabilization via connexin43 hemichannels induced by metabolic inhibition
dc.typeartículo
dc.volumen1852
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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