Biochimica et biophysica acta
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Biochim. Biophys. Acta · Oct 2016
Dexamethasone-induced muscular atrophy is mediated by functional expression of connexin-based hemichannels.
Long-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. ⋯ Finally, a prolonged DEX treatment (7days) 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.
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Biochim. Biophys. Acta · Oct 2016
Tideglusib, a chemical inhibitor of GSK3β, attenuates hypoxic-ischemic brain injury in neonatal mice.
Hypoxia-ischemia is an important cause of brain injury and neurological morbidity in the newborn infants. The activity of glycogen synthase kinase-3β (GSK-3β) is up-regulated following neonatal stroke. Tideglusib is a GSK-3β inhibitor which has neuroprotective effects against neurodegenerative diseases in clinical trials. However, the effect of tideglusib on hypoxic-ischemic (HI) brain injury in neonates is still unknown. ⋯ Tideglusib is a potential compound for the prevention or treatment of hypoxic-ischemic brain injury in neonates.