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פותח על ידי קלירמאש פתרונות בע"מ -
Halofuginone promotes satellite cell activation and survival in muscular dystrophies
Year:
2016
Authors :
פינס, מרק
;
.
Volume :
1862
Co-Authors:
Barzilai-Tutsch, H., Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
Bodanovsky, A., Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
Maimon, H., Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
Pines, M., Institute of Animal Science, The Volcani Center, Bet Dagan, Israel
Halevy, O., Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
Facilitators :
From page:
1
To page:
11
(
Total pages:
11
)
Abstract:
Halofuginone is a leading agent in preventing fibrosis and inflammation in various muscular dystrophies. We hypothesized that in addition to these actions, halofuginone directly promotes the cell-cycle events of satellite cells in the mdx and dysf-/- mouse models of early-onset Duchenne muscular dystrophy and late-onset dysferlinopathy, respectively. In both models, addition of halofuginone to freshly prepared single gastrocnemius myofibers derived from 6-week-old mice increased BrdU incorporation at as early as 18h of incubation, as well as phospho-histone H3 (PHH3) and MyoD protein expression in the attached satellite cells, while having no apparent effect on myofibers derived from wild-type mice. BrdU incorporation was abolished by an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated protein kinase, suggesting involvement of this pathway in mediating halofuginone's effects on cell-cycle events. In cultures of myofibers and myoblasts isolated from dysf-/- mice, halofuginone reduced Bax and induced Bcl2 expression levels and induced Akt phosphorylation in a time-dependent manner. Addition of an inhibitor of the phosphinositide-3-kinase/Akt pathway reversed the halofuginone-induced cell survival, suggesting this pathway's involvement in mediating halofuginone's effects on survival. Thus, in addition to its known role in inhibiting fibrosis and inflammation, halofuginone plays a direct role in satellite cell activity and survival in muscular dystrophies, regardless of the mutation. These actions are of the utmost importance for improving muscle pathology and function in muscular dystrophies. © 2015 Elsevier B.V..
Note:
Related Files :
animal cell
animal experiment
animal model
animal tissue
apoptosis
drug effect
dysferlinopathy
Male
Muscular dystrophy
עוד תגיות
תוכן קשור
More details
DOI :
10.1016/j.bbadis.2015.10.007
Article number:
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
32566
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 01:10
Scientific Publication
Halofuginone promotes satellite cell activation and survival in muscular dystrophies
1862
Barzilai-Tutsch, H., Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
Bodanovsky, A., Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
Maimon, H., Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
Pines, M., Institute of Animal Science, The Volcani Center, Bet Dagan, Israel
Halevy, O., Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
Halofuginone promotes satellite cell activation and survival in muscular dystrophies
Halofuginone is a leading agent in preventing fibrosis and inflammation in various muscular dystrophies. We hypothesized that in addition to these actions, halofuginone directly promotes the cell-cycle events of satellite cells in the mdx and dysf-/- mouse models of early-onset Duchenne muscular dystrophy and late-onset dysferlinopathy, respectively. In both models, addition of halofuginone to freshly prepared single gastrocnemius myofibers derived from 6-week-old mice increased BrdU incorporation at as early as 18h of incubation, as well as phospho-histone H3 (PHH3) and MyoD protein expression in the attached satellite cells, while having no apparent effect on myofibers derived from wild-type mice. BrdU incorporation was abolished by an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated protein kinase, suggesting involvement of this pathway in mediating halofuginone's effects on cell-cycle events. In cultures of myofibers and myoblasts isolated from dysf-/- mice, halofuginone reduced Bax and induced Bcl2 expression levels and induced Akt phosphorylation in a time-dependent manner. Addition of an inhibitor of the phosphinositide-3-kinase/Akt pathway reversed the halofuginone-induced cell survival, suggesting this pathway's involvement in mediating halofuginone's effects on survival. Thus, in addition to its known role in inhibiting fibrosis and inflammation, halofuginone plays a direct role in satellite cell activity and survival in muscular dystrophies, regardless of the mutation. These actions are of the utmost importance for improving muscle pathology and function in muscular dystrophies. © 2015 Elsevier B.V..
Scientific Publication
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