Dexamethasone-induced muscular atrophy is mediated by functional expression of connexin-based hemichannels

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

dc.creatorCea, Luis A
dc.creatorBalboa, Elisa
dc.creatorPuebla, Carlos
dc.creatorVargas-Ríos, Aníbal Antonio
dc.creatorCisterna-Irrazabal, Bruno Alejandro
dc.creatorEscamilla, Rosalba
dc.creatorRegueira, Tomas
dc.creatorSáez-Carreño, Juan Carlos
dc.date2021-08-23T22:59:16Z
dc.date2022-07-07T14:56:17Z
dc.date2021-08-23T22:59:16Z
dc.date2022-07-07T14:56:17Z
dc.date2016
dc.date.accessioned2023-08-21T21:47:33Z
dc.date.available2023-08-21T21:47:33Z
dc.identifier1150291
dc.identifier1150291
dc.identifierhttps://hdl.handle.net/10533/252556
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8286476
dc.descriptionLong-term treatment with high glucocorticoid doses induces skeletal muscle atrophy. However, the molecular mechanism of such atrophy remains unclear. We evaluated the possible involvement of connexin-based hemichannels (Cx HCs) in muscle atrophy induced by dexamethasone (DEX), a synthetic glucocorticoid, on control (Cx43(fl/fl)Cx45(fl/fl)) and Cx43/Cx45 expression-deficient (Cx43(fl/fl)Cx45(fl/fl):Myo-Cre) skeletal myofibers. Myofibers of Cx43(fl/fl)Cx45(fl/fl) mice treated with DEX (5 h) expressed several proteins that form non-selective membrane channels (Cx39, Cx43, Cx45, Panxi, P2X7 receptor and TRPV2). After 5 h DEX treatment in vivo, myofibers of Cx43(fl/fl)Cx45(fl/fl) mice showed Evans blue uptake, which was absent in myofibers of Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice. Similar results were obtained in vitro using ethidium as an HC permeability probe, and DEX-induced dye uptake in control myofibers was blocked by P2X(7) receptor inhibitors. DEX also induced a significant increase in basal intracellular Ca2+ signal and a reduction in resting membrane potential in Cx43(fl/fl)Cx45(fl/fl) myofibers, changes that were not elicited by myofibers deficient in Cx43/Cx45 expression. Moreover, treatment with DEX induced NF kappa B activation and increased mRNA levels of TNF-alpha. in control but not in Cx43(fl/fl)Cx45(fl/fl) expression-deficient myofibers. Finally, a prolonged DEX treatment (7 days) increased atrogin-1 and Murf-1 and reduced the cross sectional area of Cx43(fl/fl)Cx45(fl/fl) myofibers, but these parameters remained unaffected in Cx43(fl/fl)Cx45(fl/fl):Myo-Cre myofibers. Therefore, DEX-induced expression of Cx43 and Cx45 plays a critical role in early sarcolemma changes that lead to atrophy. Consequently, this side effect of chronic glucocorticoid treatment might be avoided by co-administration with a Cx HC blocker. (C) 2016 Elsevier B.V. All rights reserved.
dc.descriptionRegular 2015
dc.descriptionFONDECYT
dc.descriptionFONDECYT
dc.languageeng
dc.relationhandle/10533/111557
dc.relationhandle/10533/111541
dc.relationhandle/10533/108045
dc.relationhttps://doi.org/10.1016/j.bbadis.2016.07.003
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsinfo:eu-repo/semantics/article
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleDexamethasone-induced muscular atrophy is mediated by functional expression of connexin-based hemichannels
dc.titleBIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/publishedVersion


Este ítem pertenece a la siguiente institución