Caspase 3 Expression Correlates With Skeletal Muscle Apoptosis in Duchenne and Facioscapulo Human Muscular Dystrophy. A Potential Target for Pharmacological Treatment?

Sandri, Marco; Meslemani, A. H. El; Sandri, Claudia; Schjerling, P.; Vissing, Kristian; Andersen, Jesper L.; Rossini, Katia; Carraro, Ugo; Angelini, Corrado

doi:10.1093/jnen/60.3.302

Cited by 122 publications

(100 citation statements)

References 28 publications

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“…123). Indeed, apoptosis has been suggested to account for muscle atrophy in many diseases, such as skeletal muscle denervation, immobilization, chronic heart failure, skeletal muscle aging, and muscular dystrophy (Sandri et al, 1998;Libera et al, 1999;Vescovo et al, 2000;Sandri et al, 2001;Pollack et al, 2002;Dirks and Leeuwenburgh, 2002;Siu and Alway, 2005;Machida and Booth, 2005;Jejurikar et al, 2006;Chung and Ng, 2006;Siu and Alway, 2009;Wohlgemuth et al, 2010;Narasimhan et al, 2014). Skeletal muscle abnormalities in PD have been reported to include inflammatory myopathies (Gdynia et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Elevated levels of p53 and active caspase-3 have been reported in many muscular diseases, such as aging skeletal muscle and sarcopenia (Chung and Ng, 2006;Marzetti and Leeuwenburgh, 2006). Moreover, apoptosis has been reported to contribute to the muscle atrophy and loss in muscular diseases (Sandri et al, 1998;Libera et al, 1999;Vescovo et al, 2000;Sandri et al, 2001;Pollack et al, 2002;Dirks and Leeuwenburgh, 2002;Siu and Alway, 2005;Machida and Booth, 2005;Jejurikar et al, 2006;Chung and Ng, 2006;Siu and Alway, 2009;Wohlgemuth et al, 2010;Narasimhan et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

Erekat

2015

The Anatomical Record

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Apoptosis has been implicated in the pathogenesis of Parkinson disease (PD). Parkinson disease is characterized by skeletal muscle abnormalities. The aim of this study is to illustrate the impact of PD induction on the expression of apoptotic mediators. Twenty normal albino mice were randomly selected and equally divided in control and PD groups. Chronic Parkinsonism was induced in the PD group using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTP/p). After that, samples from gastrocnemius muscles were evaluated by immunohistochemistry to examine the expression of p53 and active caspase-3 in the two groups of animals. P53 and active caspase-3 expression was significantly higher in gastrocnemius skeletal muscle in PD mice compared with that in the control mice (P value <0.01). Furthermore, we show PD gastrocnemius muscle atrophy measured by significant reduction (P < 0.01) in the muscle fiber cross-sectional area. Thus, our present data suggest that PD induction increased the expression of the apoptotic mediators p53 and active caspase-3 in gastrocnemius muscle, indicating the induction of apoptosis, which was correlative with gastrocnemius muscle atrophy subsequent to the induction of PD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

Erekat

2015

The Anatomical Record

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“…Apoptosis in primary myotubes was evident in merosin, dystrophin and dystrophin-associated proteindeficient cell lines. 48,49 Recently, Ullrich congenital dystrophy, caused by collagen-VI mutations, presented an increased occurrence of spontaneous apoptosis. 50,51 At 15 days of culture, we observed a statistically significant decrease in the number of myonuclei in DM1 patients and concomitant evidences of atrophy.…”

Section: Discussionmentioning

confidence: 99%

Normal myogenesis and increased apoptosis in myotonic dystrophy type-1 muscle cells

et al. 2010

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Myotonic dystrophy (DM) is caused by a (CTG) n expansion in the 3 0 -untranslated region of DMPK gene. Mutant transcripts are retained in nuclear RNA foci, which sequester RNA binding proteins thereby misregulating the alternative splicing. Controversy still surrounds the pathogenesis of the DM1 muscle distress, characterized by myotonia, weakness and wasting with distal muscle atrophy. Eight primary human cell lines from adult-onset (DM1) and congenital (cDM1) patients, (CTG) n range 90-1800, were successfully differentiated into aneural-immature and contracting-innervated-mature myotubes. Morphological, immunohistochemical, RT-PCR and western blotting analyses of several markers of myogenesis indicated that in vitro differentiation-maturation of DM1 myotubes was comparable to age-matched controls. In all pathological muscle cells, (CTG) n expansions were confirmed by long PCR and RNA fluorescence in situ hybridization. Moreover, the DM1 myotubes showed the splicing alteration of insulin receptor and muscleblind-like 1 (MBNL1) genes associated with the DM1 phenotype. Considerable myotube loss and atrophy of 15-day-differentiated DM1 myotubes indicated activated catabolic pathways, as confirmed by the presence of apoptotic (caspase-3 activation, cytochrome c release, chromatin fragmentation) and autophagic (P62/LC3) markers. Z-VAD treatment significantly reduced the decrease in myonuclei number and in average width in 15-day-differentiated DM1 myotubes. We thus propose that the muscle wasting typical in DM1 is due to impairment of muscle mass maintenanceregeneration, through premature apoptotic-autophagic activation, rather than altered myogenesis. Myotonic dystrophy (DM) is a multi-systemic disorder caused by two different microsatellite expansions in non-coding regions. Together, these two mutations affect 1 out of 8000 individuals and represent the most common form of muscular dystrophy in adults. DM1 and DM2 have common symptoms such as myotonia, muscle weakness and early cataract development. 1,2 Although DM1 and DM2 initially affect different muscles (distal versus proximal), histological analysis of the muscular tissues shows common aspects such as central nucleation. The classic form of DM1 is characterized by muscle distress with myotonia, progressive muscle weakness and wasting. Atrophy has also been reported, occurring preferentially in type-1 fibers in DM1 and in type-2 in DM2. 3 DM1 but not DM2 also presents a congenital form (cDM1), characterized by a high neonatal mortality and symptoms such as hypotonia, mental retardation and respiratory distress. 4,5 DM1 is associated with an unstable (CTG) n trinucleotide expansion located in the 3 0 -untranslated (3 0 -UTR) region of the DM protein kinase (DMPK) gene on chromosome 19q13.3. The mutant DMPK transcript, containing the expanded (CTG) n sequence, accumulates in discrete nuclear foci able to sequester various nuclear factors such as RNAbinding proteins or splicing regulators, causing different and highly variable downstream deleterious effects. 2,6...

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“…50) is associated with rapid muscle degeneration and early death (51). Myofiber apoptosis is prominent in myopathies/dystrophies including DMD (10,11). In the mdx mouse model of DMD myofiber apoptosis precedes necrosis and peaks at 4 weeks of age (31).…”

Section: Fhl1 and The Splice Isoforms Kyot2 And Slimmer Domainmentioning

confidence: 99%

“…2). Myofiber apoptosis also occurs in many human myopathies including Duchenne muscular dystrophy (DMD) 3 (10,11). LIM domain-containing proteins regulate skeletal muscle development and cytoarchitecture and, when mutated, cause human myopathy.…”

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confidence: 99%

SLIMMER (FHL1B/KyoT3) Interacts with the Proapoptotic Protein Siva-1 (CD27BP) and Delays Skeletal Myoblast Apoptosis

Cottle¹,

Mcgrath²,

Wilding

et al. 2009

Journal of Biological Chemistry

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The fhl1 gene encoding four-and-a-half LIM protein-1 (FHL1) and its spliced isoform, SLIMMER, is mutated in reducing body myopathy, X-linked myopathy with postural muscle atrophy, scapuloperoneal myopathy, and rigid spine syndrome. In this study we have identified a novel function for SLIMMER in delaying skeletal muscle apoptosis via an interaction with the proapoptotic protein Siva-1. Siva-1 was identified as a SLIMMER-specific-interacting protein using yeast two-hybrid screening, direct-binding studies, and glutathione S-transferase pulldown analysis of murine skeletal muscle lysates. In C2C12 skeletal myoblasts, SLIMMER and Siva co-localized in the nucleus; however, both proteins exhibited redistribution to the cytoplasm following the differentiation of mononucleated myoblasts to multinucleated myotubes. In sections of mature skeletal muscle from wild type mice, SLIMMER and Siva-1 colocalized at the Z-line. SLIMMER and Siva-1 were also enriched in Pax-7-positive satellite cells, muscle stem cells that facilitate repair and regeneration. Significantly, SLIMMER delayed Siva-1-dependent apoptosis in C2C12 myoblasts. In skeletal muscle sections from the mdx mouse model of Duchenne muscular dystrophy, SLIMMER and Siva-1 co-localized in the nucleus of apoptotic myofibers. Therefore, SLIMMER may protect skeletal muscle from apoptosis.

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Caspase 3 Expression Correlates With Skeletal Muscle Apoptosis in Duchenne and Facioscapulo Human Muscular Dystrophy. A Potential Target for Pharmacological Treatment?

Cited by 122 publications

References 28 publications

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

Normal myogenesis and increased apoptosis in myotonic dystrophy type-1 muscle cells

SLIMMER (FHL1B/KyoT3) Interacts with the Proapoptotic Protein Siva-1 (CD27BP) and Delays Skeletal Myoblast Apoptosis

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