Linoleic acid induces opening of connexin26 hemichannels through a PI3K/Akt/Ca2+-dependent pathway

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dc.contributor.authorFigueroa, Vania
dc.contributor.authorSaez, J Pablo
dc.contributor.authorSalas, Jose
dc.contributor.authorRetamal, Mauricio
dc.date.accessioned2017-04-06T19:12:43Z
dc.date.available2017-04-06T19:12:43Z
dc.date.issued2013
dc.descriptionCentro de Fisiología Celular e Integrativa
dc.description.abstractConnexin hemichannel (Cx HC) opening is involved in physiological and pathological processes, allowing the cellular release of autocrine/paracrine signaling molecules. Linoleic acid (LA) is known to modulate the functional state of connexin46 (Cx46) HCs. However, the molecular mechanism involved in this effect, or whether LA affects HCs constituted of other connexins, remains unknown. Here, we report the effects of LA on HCs in HeLa cells that express Cx26, one of the main Cxs in the cochlear sensory epithelium. Cx26 HC activity (dye uptake) was increased in a concentration-dependent manner by bath application of LA and inhibited by HC blockers. Moreover, intracellular BAPTA, a Ca(2+) chelator, and PI3K/AKT inhibitors were found to reduce the LA-induced Cx26 HC opening, suggesting that the LA effect is mediated by an increase of free intracellular Ca(2+) concentration and activation of the PI3K/Akt-dependent pathway. The LA-induced increase in free intracellular Ca(2+) concentration was mainly due to Ca(2+) influx through Cx26 HCs. In addition, the involvement of -SH groups was ruled out, because dithiothreitol (DTT) did not block the LA-induced dye uptake. LA also increased the membrane current mediated by Cx26 HCs expressed in Xenopus oocytes and the dye uptake in HeLa cells expressing Cxs 32, 43 or 45. Since LA is an essential polyunsaturated fatty acid, its effect on HCs might be relevant to cell growth as well as to cellular functions of differentiated cells such as audition.
dc.format.extent1
dc.identifier.citationBiochim Biophys Acta Volume 1828, Issue 3, March 2013, Pages 1169–1179
dc.identifier.urihttp://hdl.handle.net/11447/1104
dc.identifier.urihttp://dx.doi.org/10.1016/j.bbamem.2012.12.006
dc.language.isoen_US
dc.publisherElsevier
dc.subjectPolyunsaturated fatty acid
dc.subjectHemichannel
dc.subjectCx26
dc.subjectIntracellular calcium
dc.subjectHearing loss
dc.titleLinoleic acid induces opening of connexin26 hemichannels through a PI3K/Akt/Ca2+-dependent pathway
dc.typeArtículo

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