Abstract
In recent years, histochemistry at light and electron microscopy has increasingly been applied to investigate basic mechanisms of skeletal muscle diseases; in particular, the study in situ of skeletal muscle cell nuclei proved to be crucial for elucidating some pathogenetic mechanisms of skeletal muscle wasting in myotonic dystrophy (DM) and sarcopenia. DM is an autosomal dominant disorder whose multisystemic features originate form nucleotide expansions: (CTG)n in the dystrophy myotonic protein kinase (DMPK) gene on chromosome 19q13 in DM type 1 (DM1), or (CCTG)n in intron 1 of the CNBP gene (previously know as zinc finger 9 gene, ZNF9) on chromosome 3q21 in DM type 2 (DM2). Sarcopenia is an age-related condition characterized by the decline of muscle mass, strength and function, whose causes are still poorly known and probably manifold (e.g., altered levels of anabolic hormones and inflammatory mediators, impairment of proteolytic and autophagic pathways, mitochondrial or neuromuscular dysfunction, loss of satellite cells). Interestingly, skeletal muscles in both DM and sarcopenia show myofibre atrophy, fibre size variability and centrally located nuclei, as well as a reduced satellite cells' effectiveness. Based on ex vivo and in vitro studies, we have demonstrated that both myofibres and satellite cells of DM and sarcopenic muscles exhibit a massive nuclear rearrangement of the structural and molecular factors responsible for pre-mRNA transcription and maturation: the impairment in the pre-mRNA post transcriptional pathways would thus account for the aging-reminiscent muscle phenotype of DM patients suggesting that the skeletal muscle wasting observed in DM and sarcopenia may result from similar cellular mechanisms.
| Original language | English |
|---|---|
| Article number | 196 |
| Journal | Frontiers in Aging Neuroscience |
| Volume | 6 |
| Issue number | JUL |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- Cell nucleus
- Immunohistochemistry
- Myotonic dystrophy
- Sarcopenia
- Splicing
- Transmission electron microscopy
ASJC Scopus subject areas
- Ageing
- Cognitive Neuroscience
Cite this
Rna transcription and maturation in skeletal muscle cells are similarly impaired in myotonic dystrophy and sarcopenia : The ultrastructural evidence. / Malatesta, Manuela; Cardani, Rosanna; Pellicciari, Carlo; Meola, Giovanni.
In: Frontiers in Aging Neuroscience, Vol. 6, No. JUL, 196, 2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Rna transcription and maturation in skeletal muscle cells are similarly impaired in myotonic dystrophy and sarcopenia
T2 - The ultrastructural evidence
AU - Malatesta, Manuela
AU - Cardani, Rosanna
AU - Pellicciari, Carlo
AU - Meola, Giovanni
PY - 2014
Y1 - 2014
N2 - In recent years, histochemistry at light and electron microscopy has increasingly been applied to investigate basic mechanisms of skeletal muscle diseases; in particular, the study in situ of skeletal muscle cell nuclei proved to be crucial for elucidating some pathogenetic mechanisms of skeletal muscle wasting in myotonic dystrophy (DM) and sarcopenia. DM is an autosomal dominant disorder whose multisystemic features originate form nucleotide expansions: (CTG)n in the dystrophy myotonic protein kinase (DMPK) gene on chromosome 19q13 in DM type 1 (DM1), or (CCTG)n in intron 1 of the CNBP gene (previously know as zinc finger 9 gene, ZNF9) on chromosome 3q21 in DM type 2 (DM2). Sarcopenia is an age-related condition characterized by the decline of muscle mass, strength and function, whose causes are still poorly known and probably manifold (e.g., altered levels of anabolic hormones and inflammatory mediators, impairment of proteolytic and autophagic pathways, mitochondrial or neuromuscular dysfunction, loss of satellite cells). Interestingly, skeletal muscles in both DM and sarcopenia show myofibre atrophy, fibre size variability and centrally located nuclei, as well as a reduced satellite cells' effectiveness. Based on ex vivo and in vitro studies, we have demonstrated that both myofibres and satellite cells of DM and sarcopenic muscles exhibit a massive nuclear rearrangement of the structural and molecular factors responsible for pre-mRNA transcription and maturation: the impairment in the pre-mRNA post transcriptional pathways would thus account for the aging-reminiscent muscle phenotype of DM patients suggesting that the skeletal muscle wasting observed in DM and sarcopenia may result from similar cellular mechanisms.
AB - In recent years, histochemistry at light and electron microscopy has increasingly been applied to investigate basic mechanisms of skeletal muscle diseases; in particular, the study in situ of skeletal muscle cell nuclei proved to be crucial for elucidating some pathogenetic mechanisms of skeletal muscle wasting in myotonic dystrophy (DM) and sarcopenia. DM is an autosomal dominant disorder whose multisystemic features originate form nucleotide expansions: (CTG)n in the dystrophy myotonic protein kinase (DMPK) gene on chromosome 19q13 in DM type 1 (DM1), or (CCTG)n in intron 1 of the CNBP gene (previously know as zinc finger 9 gene, ZNF9) on chromosome 3q21 in DM type 2 (DM2). Sarcopenia is an age-related condition characterized by the decline of muscle mass, strength and function, whose causes are still poorly known and probably manifold (e.g., altered levels of anabolic hormones and inflammatory mediators, impairment of proteolytic and autophagic pathways, mitochondrial or neuromuscular dysfunction, loss of satellite cells). Interestingly, skeletal muscles in both DM and sarcopenia show myofibre atrophy, fibre size variability and centrally located nuclei, as well as a reduced satellite cells' effectiveness. Based on ex vivo and in vitro studies, we have demonstrated that both myofibres and satellite cells of DM and sarcopenic muscles exhibit a massive nuclear rearrangement of the structural and molecular factors responsible for pre-mRNA transcription and maturation: the impairment in the pre-mRNA post transcriptional pathways would thus account for the aging-reminiscent muscle phenotype of DM patients suggesting that the skeletal muscle wasting observed in DM and sarcopenia may result from similar cellular mechanisms.
KW - Cell nucleus
KW - Immunohistochemistry
KW - Myotonic dystrophy
KW - Sarcopenia
KW - Splicing
KW - Transmission electron microscopy
UR - http://www.scopus.com/inward/record.url?scp=84904640116&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904640116&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2014.00196
DO - 10.3389/fnagi.2014.00196
M3 - Article
AN - SCOPUS:84904640116
VL - 6
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
IS - JUL
M1 - 196
ER -