Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1852, Issue 7, Pages 1268-1277Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2015.03.004
Keywords
Surface hemichannels; Intracellular Ca2+; Oxygen-glucose deprivation; Akt activation
Funding
- Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) [1111033]
- Chilean Science Millennium Institute [P09-022-F]
- Fondo de Investigacion Avanzada en Areas Prioritarias (FONDAP) [15130011]
- US National Insitutes of Health [GM55632]
- Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT), Santiago, Chile [21080284, AT-24100026]
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Connexin 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.
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