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Nishimura, Y, Bittel, AJ, Stead, CA, Chen, Y-W and Burniston, JG (2023) Facioscapulohumeral muscular dystrophy is associated with altered myoblast proteome dynamics. Molecular & Cellular Proteomics, 22 (8). ISSN 1535-9476
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Facioscapulohumeral muscular dystrophy is associated with altered myoblast proteome dynamics.pdf - Published Version Available under License Creative Commons Attribution. Download (4MB) | Preview |
Abstract
Proteomic studies in facioscapulohumeral muscular dystrophy (FSHD) could offer new insight to disease mechanisms underpinned by post-transcriptional processes. We used stable isotope (deuterium oxide; D2O) labelling and peptide mass spectrometry to investigate the abundance and turnover rates of proteins in cultured muscle cells from 2 individuals affected by FSHD and their unaffected siblings (UASb). We measured the abundance of 4420 proteins and the turnover rate of 2324 proteins in each (n = 4) myoblast sample. FSHD myoblasts exhibited a greater abundance but slower turnover rate of subunits of mitochondrial respiratory complexes and mitochondrial ribosomal proteins, which may indicate an accumulation of ‘older’ less viable mitochondrial proteins in myoblasts from individuals affected by FSHD. Treatment with a 2’-O-methoxyethyl modified antisense oligonucleotide targeting exon 3 of the double homeobox 4 (DUX4) transcript tended to reverse mitochondrial protein dysregulation in FSHD myoblasts, indicating the effect on mitochondrial proteins may be a DUX4-dependent mechanism. Our results highlight the importance of post-transcriptional processes and protein turnover in FSHD pathology and provide a resource for the FSHD research community to explore this burgeoning aspect of FSHD.
| Item Type: | Article |
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| Uncontrolled Keywords: | Biochemistry & Molecular Biology |
| Subjects: | R Medicine > RC Internal medicine > RC1200 Sports Medicine |
| Divisions: | Sport & Exercise Sciences |
| Publisher: | Elsevier |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 22 Jun 2023 10:09 |
| Last Modified: | 25 Jul 2023 14:45 |
| DOI or ID number: | 10.1016/j.mcpro.2023.100605 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/20013 |
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