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פותח על ידי קלירמאש פתרונות בע"מ -
A promotive effect for halofuginone on membrane repair and synaptotagmin-7 levels in muscle cells of dysferlin-null mice
Year:
2018
Source of publication :
Authors :
פינס, מרק
;
.
Volume :
27
Co-Authors:

Barzilai-Tutsch, H., Department of Animal Sciences, Hebrew University of Jerusalem, PO Box 12, Rehovot, 76100, Israel; Dewulf, M., Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie-Centre de Recherche, PSL Research University, INSERM U1143, Centre National de la Recherche Scientifique, UMR 3666, Paris, France; Lamaze, C., Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie-Centre de Recherche, PSL Research University, INSERM U1143, Centre National de la Recherche Scientifique, UMR 3666, Paris, France; Browne, G.B., Center for Research in Myology, CNRS FRE 3617, UPMC Univ Paris 06, UM76, INSERM U974, Sorbonne Universités, Paris, France; ; Halevy, O., Department of Animal Sciences, Hebrew University of Jerusalem, PO Box 12, Rehovot, 76100, Israel

Facilitators :
From page:
2817
To page:
2829
(
Total pages:
13
)
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 disease progress and that sytnaptotagmin-7 may be compensating for the lack of dysferlin at least with regard to membrane resealing post-injury. While halofuginone did not affect patch-repair-complex key proteins, it further enhanced Syt-7 levels and its spread across the cytosol in dysf-/- myofibers and muscle tissue, and increased its colocalization with lysosomes. Together, the data imply a novel role for halofuginone in membrane-resealing events with Syt-7 possibly taking part in these events. © The Author(s) 2018.

Note:
Related Files :
Dysferlinopathies
dysferlinopathy
membrane
mice
muscle cell
Muscular dystrophy
Muscular Dystrophy, Animal
skeletal muscle cell
עוד תגיות
תוכן קשור
More details
DOI :
10.1093/hmg/ddy185
Article number:
0
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
37879
Last updated date:
02/03/2022 17:27
Creation date:
07/11/2018 10:36
Scientific Publication
A promotive effect for halofuginone on membrane repair and synaptotagmin-7 levels in muscle cells of dysferlin-null mice
27

Barzilai-Tutsch, H., Department of Animal Sciences, Hebrew University of Jerusalem, PO Box 12, Rehovot, 76100, Israel; Dewulf, M., Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie-Centre de Recherche, PSL Research University, INSERM U1143, Centre National de la Recherche Scientifique, UMR 3666, Paris, France; Lamaze, C., Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie-Centre de Recherche, PSL Research University, INSERM U1143, Centre National de la Recherche Scientifique, UMR 3666, Paris, France; Browne, G.B., Center for Research in Myology, CNRS FRE 3617, UPMC Univ Paris 06, UM76, INSERM U974, Sorbonne Universités, Paris, France; ; Halevy, O., Department of Animal Sciences, Hebrew University of Jerusalem, PO Box 12, Rehovot, 76100, Israel

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

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 disease progress and that sytnaptotagmin-7 may be compensating for the lack of dysferlin at least with regard to membrane resealing post-injury. While halofuginone did not affect patch-repair-complex key proteins, it further enhanced Syt-7 levels and its spread across the cytosol in dysf-/- myofibers and muscle tissue, and increased its colocalization with lysosomes. Together, the data imply a novel role for halofuginone in membrane-resealing events with Syt-7 possibly taking part in these events. © The Author(s) 2018.

Scientific Publication
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