Mostrar el registro sencillo del ítem

De novo expression of functional connexins 43 and 45 hemichannels increases sarcolemmal permeability of skeletal myofibers during endotoxemia

dc.contributor.authorCea L.A.
dc.contributor.authorBalboa E.
dc.contributor.authorVargas A.A.
dc.contributor.authorPuebla C.
dc.contributor.authorBrañes M.C.
dc.contributor.authorEscamilla R.
dc.contributor.authorRegueira T.
dc.contributor.authorSáez J.C.
dc.date.accessioned2020-09-02T22:14:47Z
dc.date.available2020-09-02T22:14:47Z
dc.date.issued2019
dc.identifier10.1016/j.bbadis.2019.06.014
dc.identifier.citation1865, 10, 2765-2773
dc.identifier.issn09254439
dc.identifier.urihttps://hdl.handle.net/20.500.12728/3981
dc.descriptionEndotoxemia caused by bacterial lipopolysaccharides (LPSs) leads to severe skeletal muscular deterioration, starting with higher membrane permeability and decline in resting membrane potential (RMP). However, the molecular mechanism of such changes remains unclear. Here, we evaluated the possible involvement of connexin43- and connexin45-based hemichannels (Cx43 and Cx45 HCs, respectively) as putative mediators of sarcolemmal dysfunctions induced by LPS in control (Cx43fl/flCx45fl/fl) and Cx43/Cx45 expression-deficient (Cx43fl/flCx45fl/fl:Myo-Cre) skeletal mice myofibers. At 5 h of endotoxemia, control myofibers presented Cx43 and Cx45 proteins forming functional HCs. Additionally, myofibers from endotoxic control mice showed dye uptake in vivo, which was inhibited by carbenoxolone, a Cx HC blocker. A similar increase in membrane permeability was observed in myofibers freshly isolated from skeletal muscle of mice treated for 5 h with LPS, which was blocked by the Cx HC blocker and was absent in myofibers from mice simultaneously treated with LPS and boldine, which is a Cx HC blocker. The increase in sarcolemmal permeability was mimicked by isolated myofibers treated with pro-inflammatory cytokines (TNF-α and IL-1β) and occurred at 5 h after treatment. Endotoxemia also induced a significant increase in basal intracellular Ca2+ signal and a drop in RMP in control myofibers. These two changes were not elicited by myofibers deficient in Cx43/Cx45 expression. Therefore, sarcolemmal dysfunction characterizing endotoxemia is largely explained by the expression of functional Cx43 and Cx45 HCs. Hence, current therapy options for individuals suffering from endotoxic shock could be greatly improved with selective Cx HC inhibitors avoiding the underlying skeletal muscle dysfunction. © 2019 Elsevier B.V.
dc.language.isoen
dc.publisherElsevier B.V.
dc.subjectConnexons
dc.subjectLPS
dc.subjectMembrane permeability
dc.subjectPro-inflammatory cytokines
dc.subjectResting membrane potential
dc.subjectcarbenoxolone
dc.subjectconnexin 43
dc.subjectconnexin 45
dc.subjectinterleukin 1beta
dc.subjectlipopolysaccharide
dc.subjecttumor necrosis factor
dc.subjectcalcium
dc.subjectconnexin 43
dc.subjectconnexin 45
dc.subjectcytokine
dc.subjectgap junction protein
dc.subjectglucocorticoid
dc.subjectlipopolysaccharide
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectcontrolled study
dc.subjectendotoxemia
dc.subjectmale
dc.subjectmembrane permeability
dc.subjectmembrane steady potential
dc.subjectmouse
dc.subjectmuscle tissue
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectsarcolemma
dc.subjectskeletal muscle
dc.subjectanimal
dc.subjectcell membrane
dc.subjectcomplication
dc.subjectdisease model
dc.subjectdrug effect
dc.subjectendotoxemia
dc.subjectgenetics
dc.subjectknockout mouse
dc.subjectmembrane potential
dc.subjectmetabolism
dc.subjectpathology
dc.subjectpermeability
dc.subjectskeletal muscle
dc.subjectAnimals
dc.subjectCalcium
dc.subjectCell Membrane
dc.subjectConnexin 43
dc.subjectConnexins
dc.subjectCytokines
dc.subjectDisease Models, Animal
dc.subjectEndotoxemia
dc.subjectGlucocorticoids
dc.subjectLipopolysaccharides
dc.subjectMale
dc.subjectMembrane Potentials
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMuscle, Skeletal
dc.subjectPermeability
dc.titleDe novo expression of functional connexins 43 and 45 hemichannels increases sarcolemmal permeability of skeletal myofibers during endotoxemia
dc.typeArticle


Ficheros en el ítem

Thumbnail
Nombre:
item_2-s2.0-85068026151.pdf
Tamaño:
4.216Kb
Formato:
PDF
Ver/

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem