A promotive effect for halofuginone on membrane repair and synaptotagmin-7 levels in muscle cells of dysferlin-null mice

Human Molecular Genetics
Hila Barzilai-TutschOrna Halevy

Abstract

In the absence of dysferlin, skeletal muscle cells fail to reseal properly after injury, resulting in slow progress of the dysferlinopathy muscular dystrophy (MD). Halofuginone, a leading agent in preventing fibrosis in MDs, was tested for its effects on membrane resealing post-injury. A hypo-osmotic shock assay on myotubes derived from wild-type (Wt) and dysferlin-null (dysf-/-) mice revealed that pre-treatment with halofuginone reduces the percentage of membrane-ruptured myotubes only in dysf-/- myotubes. In laser-induced injury of isolated myofibers, halofuginone decreased the amount of FM1-43 at the injury site of dysf-/- myofibers while having no effect on Wt myofibers. These results implicate halofuginone in ameliorating muscle-cell membrane integrity in dysf-/- mice. Halofuginone increased lysosome scattering across the cytosol of dysf-/- primary myoblasts, in a protein kinase/extracellular signal-regulated protein kinase and phosphoinositide 3 kinase/Akt-dependent manner, in agreement with an elevation in lysosomal exocytotic activity in these cells. A spatial- and age-dependent synaptotagmin-7 (Syt-7) expression pattern was shown in dysf-/- versus Wt mice, suggesting that these pattern alterations are related to the di...Continue Reading

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Citations

May 22, 2020·Cell Biology International·Asuman Demiroglu-ZergerogluRonald R Odongo
Aug 17, 2019·Biomaterials·Jason WangNenad Bursac
Feb 24, 2021·Cellular and Molecular Life Sciences : CMLS·Mónica C Quiñones-Frías, J Troy Littleton
Jul 3, 2021·International Journal of Molecular Sciences·Sharon MordechayOrna Halevy
Sep 28, 2021·Human Molecular Genetics·Sarah J SmithJames J Dowling

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