Vitamin E Blocks Connexin Hemichannels and Prevents Deleterious Effects of Glucocorticoid Treatment on Skeletal Muscles

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dc.contributor.authorBalboa, Elisa
dc.contributor.authorSaavedra, Fujiko
dc.contributor.authorCea, Luis A.
dc.contributor.authorRamirez, Valeria
dc.contributor.authorEscamilla, Rosalba
dc.contributor.authorVargas, Anibal A.
dc.contributor.authorRegueira, Tomas
dc.contributor.authorSaez, Juan C.
dc.date.accessioned2025-01-23T19:50:52Z
dc.date.available2025-01-23T19:50:52Z
dc.date.issued2020
dc.description.abstractGlucocorticoids are frequently used as anti-inflammatory and immunosuppressive agents. However, high doses and/or prolonged use induce undesired secondary effects such as muscular atrophy. Recently, de novo expression of connexin43 and connexin45 hemichannels (Cx43 HCs and Cx45 HCs, respectively) has been proposed to play a critical role in the mechanism underlying myofiber atrophy induced by dexamethasone (Dex: a synthetic glucocorticoid), but their involvement in specific muscle changes promoted by Dex remains poorly understood. Moreover, treatments that could prevent the undesired effects of glucocorticoids on skeletal muscles remain unknown. In the present work, a 7-day Dex treatment in adult mice was found to induce weight loss and skeletal muscle changes including expression of functional Cx43/Cx45 HCs, elevated atrogin immunoreactivity, atrophy, oxidative stress and mitochondrial dysfunction. All these undesired effects were absent in muscles of mice simultaneously treated with Dex and vitamin E (VitE). Moreover, VitE was found to rapidly inhibit the activity of Cx HCs in freshly isolated myofibers of Dex treated mice. Exposure to alkaline pH induced free radical generation only in HeLa cells expressing Cx43 or Cx45 where Ca2+ was present in the extracellular milieu, response that was prevented by VitE. Besides, VitE and two other anti-oxidant compounds, Tempol and Resveratrol, were found to inhibit Cx43 HCs in HeLa cells transfectants. Thus, we propose that in addition to their intrinsic anti-oxidant potency, some antioxidants could be used to reduce expression and/or opening of Cx HCs and consequently reduce the undesired effect of glucocorticoids on skeletal muscles.
dc.fuente.origenWOS
dc.identifier.doi10.3390/ijms21114094
dc.identifier.eissn1422-0067
dc.identifier.urihttps://doi.org/10.3390/ijms21114094
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100560
dc.identifier.wosidWOS:000543400300356
dc.issue.numero11
dc.language.isoen
dc.revistaInternational journal of molecular sciences
dc.rightsacceso restringido
dc.subjectconnexons
dc.subjectmitochondrial dysfunction
dc.subjectoxidative stress
dc.subjectmuscle atrophy
dc.subjectdexamethasone
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleVitamin E Blocks Connexin Hemichannels and Prevents Deleterious Effects of Glucocorticoid Treatment on Skeletal Muscles
dc.typeartículo
dc.volumen21
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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