scholarly journals Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy

2013 ◽  
pp. 2943 ◽  
Author(s):  
Mehdi Shafiee Ardestani ◽  
Afzal ◽  
Zakery ◽  
Bagheri ◽  
Farjadian ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Glatiramer Acetate ◽  
Therapeutic Strategy ◽  
Myogenic Differentiation

scholarly journals PCAF Involvement in Lamin A/C-HDAC2 Interplay during the Early Phase of Muscle Differentiation

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1735
Author(s):  
Spartaco Santi ◽  
Vittoria Cenni ◽  
Cristina Capanni ◽  
Giovanna Lattanzi ◽  
Elisabetta Mattioli
Keyword(s):  
Muscular Dystrophy ◽  
Early Phase ◽  
Myogenic Differentiation ◽  
Nuclear Lamina ◽  
Muscle Differentiation ◽  
Lamin A ◽  
Histone Deacetylase 2 ◽  
Muscle Gene Expression ◽  
Muscle Gene ◽  
Human Muscle Cells

Lamin A/C has been implicated in the epigenetic regulation of muscle gene expression through dynamic interaction with chromatin domains and epigenetic enzymes. We previously showed that lamin A/C interacts with histone deacetylase 2 (HDAC2). In this study, we deepened the relevance and regulation of lamin A/C-HDAC2 interaction in human muscle cells. We present evidence that HDAC2 binding to lamin A/C is related to HDAC2 acetylation on lysine 75 and expression of p300-CBP associated factor (PCAF), an acetyltransferase known to acetylate HDAC2. Our findings show that lamin A and farnesylated prelamin A promote PCAF recruitment to the nuclear lamina and lamin A/C binding in human myoblasts committed to myogenic differentiation, while protein interaction is decreased in differentiating myotubes. Interestingly, PCAF translocation to the nuclear envelope, as well as lamin A/C-PCAF interaction, are reduced by transient expression of lamin A mutated forms causing Emery Dreifuss muscular dystrophy. Consistent with this observation, lamin A/C interaction with both PCAF and HDAC2 is significantly reduced in Emery–Dreifuss muscular dystrophy myoblasts. Overall, these results support the view that, by recruiting PCAF and HDAC2 in a molecular platform, lamin A/C might contribute to regulate their epigenetic activity required in the early phase of muscle differentiation.

T.P.5.12 Regeneration is up-regulated in Glatiramer acetate treated dy2J/dy2J mice with congenital muscular dystrophy

2009 ◽  
Vol 19 (8-9) ◽  
pp. 619
Author(s):  
O. Dadush ◽  
S. Aga-Mizrachi ◽  
K. Ettinger ◽  
R. Tabakman ◽  
M. Elbaz ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Glatiramer Acetate ◽  
Congenital Muscular Dystrophy

scholarly journals Dynamic transcriptomic analysis reveals suppression of PGC1α/ERRα drives perturbed myogenesis in facioscapulohumeral muscular dystrophy

2018 ◽  
Vol 28 (8) ◽  
pp. 1244-1259 ◽  
Author(s):  
Christopher R S Banerji ◽  
Maryna Panamarova ◽  
Johanna Pruller ◽  
Nicolas Figeac ◽  
Husam Hebaishi ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Empirical Bayes ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Myogenic Differentiation ◽  
Critical Time ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Food Supplements ◽  
Biochanin A ◽  
Time Points

Abstract Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to epigenetic derepression of D4Z4 repeats on chromosome 4q, leading to ectopic DUX4 expression. FSHD patient myoblasts have defective myogenic differentiation, forming smaller myotubes with reduced myosin content. However, molecular mechanisms driving such disrupted myogenesis in FSHD are poorly understood. We performed high-throughput morphological analysis describing FSHD and control myogenesis, revealing altered myogenic differentiation results in hypotrophic myotubes. Employing polynomial models and an empirical Bayes approach, we established eight critical time points during which human healthy and FSHD myogenesis differ. RNA-sequencing at these eight nodal time points in triplicate, provided temporal depth for a multivariate regression analysis, allowing assessment of interaction between progression of differentiation and FSHD disease status. Importantly, the unique size and structure of our data permitted identification of many novel FSHD pathomechanisms undetectable by previous approaches. For further analysis here, we selected pathways that control mitochondria: of interest considering known alterations in mitochondrial structure and function in FSHD muscle, and sensitivity of FSHD cells to oxidative stress. Notably, we identified suppression of mitochondrial biogenesis, in particular via peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α), the cofactor and activator of oestrogen-related receptor α (ERRα). PGC1α knock-down caused hypotrophic myotubes to form from control myoblasts. Known ERRα agonists and safe food supplements biochanin A, daidzein or genistein, each rescued the hypotrophic FSHD myotube phenotype. Together our work describes transcriptomic changes in high resolution that occur during myogenesis in FSHD ex vivo, identifying suppression of the PGC1α-ERRα axis leading to perturbed myogenic differentiation, which can effectively be rescued by readily available food supplements.

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