scholarly journals Cellular and Animal Models of Striated Muscle Laminopathies

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 291 ◽  
Author(s):  
Hannah A. Nicolas ◽  
Marie-Andrée Akimenko ◽  
Frédérique Tesson
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Molecular Mechanisms ◽  
Striated Muscle ◽  
Nuclear Lamina ◽  
The Other ◽  
Lamin A ◽  
Lmna Gene ◽  
Future Directions ◽  
Exon 10

The lamin A/C (LMNA) gene codes for nuclear intermediate filaments constitutive of the nuclear lamina. LMNA has 12 exons and alternative splicing of exon 10 results in two major isoforms—lamins A and C. Mutations found throughout the LMNA gene cause a group of diseases collectively known as laminopathies, of which the type, diversity, penetrance and severity of phenotypes can vary from one individual to the other, even between individuals carrying the same mutation. The majority of the laminopathies affect cardiac and/or skeletal muscles. The underlying molecular mechanisms contributing to such tissue-specific phenotypes caused by mutations in a ubiquitously expressed gene are not yet well elucidated. This review will explore the different phenotypes observed in established models of striated muscle laminopathies and their respective contributions to advancing our understanding of cardiac and skeletal muscle-related laminopathies. Potential future directions for developing effective treatments for patients with lamin A/C mutation-associated cardiac and/or skeletal muscle conditions will be discussed.

scholarly journals Chemical and immunochemical characteristics of tropomyosins from striated and smooth muscle

1974 ◽  
Vol 141 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Peter Cummins ◽  
S. Victor Perry
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Cardiac Muscle ◽  
Skeletal Muscles ◽  
Striated Muscle ◽  
Β Subunit ◽  
Muscle Type ◽  
Amphibian Species ◽  
Species Specific ◽  
Immunochemical Characteristics

1. On electrophoresis in dissociating conditions the tropomyosins isolated from skeletal muscles of mammalian, avian and amphibian species migrated as two components. These were comparable with the α and β subunits of tropomyosin present in rabbit skeletal muscle. 2. The α and β components of all skeletal-muscle tropomyosins contained 1 and 2 residues of cysteine per 34000g respectively. 3. The ratio of the amounts of α and β subunit present in skeletal muscle tropomyosins was characteristic for the muscle type. Muscle consisting of slow red fibres contained a greater proportion of β-tropomyosin than muscles consisting predominantly of white fast fibres. 4. Mammalian and avian cardiac muscle tropomyosins consisted of α-tropomyosin only. 5. Mammalian and avian smooth-muscle tropomyosins differed both chemically and immunologically from striated-muscle tropomyosins. 6. Antibody raised against rabbit skeletal α-tropomyosin was species non-specific, reacting with all other striated muscle α-tropomyosin subunits tested. 7. Antibody raised against rabbit skeletal β-tropomyosin subunit was species-specific.

scholarly journals Molecular background of impairments in skeletal muscle of heart failure patients

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
O Ivanova ◽  
M Y Komarova ◽  
E V Ignatieva ◽  
T A Lelyavina ◽  
V L Galenko ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Differentially Expressed Genes ◽  
Skeletal Muscles ◽  
Molecular Mechanisms ◽  
Class Ii ◽  
Differentially Expressed ◽  
Exercise Intolerance ◽  
Type I ◽  
Molecular Abnormalities

Abstract Background Heart failure (HF) is characterised by systematic inflammation and chronic metabolic dysregulation. HF enhances the release of pro-inflammatory cytokines, induces activation of the complement system, production of autoantibodies, and over-expression of the major histocompatibility (MHC) complex class II molecules. It is known that skeletal muscles are exposed to the immunologic injury in disease; and muscle tissue appeared to be affected by HF leading to the muscle weakness and exercise intolerance development. However, molecular abnormalities occurring in HF patients' muscles and the mechanisms underlying its development are not clarified. Purpose To understand the molecular mechanisms underlying skeletal muscle immune and non-immune impairments in HF. Methods 8 health donors and 5 HF patients with reduced ejection fraction (NYHA Class II and III) were enrolled in this study in accordance with the principles under the Declaration of Helsinki (1989). mRNA of skeletal muscle biopsies of gastrocnemius lateralis were sequenced on Illumina HiSeq. RNA-seq analysis was performed using STAR with reference genome GRCh38 and featureCounts program; differentially expressed genes (DEGs) were assessed using R package DESeq2 with FDR=0.01 and log2 fold change (l2fc) >1.5 filter; pathway analysis was performed using clusterProfiler in R (FDR=0.01). Results 1404 differentially expressed genes distinguish muscles of HF patients and controls. Among upregulated genes there are different classical MHC molecules and specific one HLA-G (l2fc=2) that has been previously shown appeared in muscles under autoimmune myopathies, and potentially protect them. Unregulated DEGs were responsible for the activation of many molecular immunological pathways: type I interferon signaling pathway (16 DEGs out of total 89), regulation of T cell proliferation (14/153), neutrophil degranulation (31/485), granulocyte differentiation (7/32), negative regulation of viral process (11/53), that indicates about specific inflammatory response in HF muscles. Response to hypoxia (22/314) and gluconeogenesis pathways (12/87) were also activated. Downregulated genes include SLC5A1 (l2fc=−4) sodium glucose cotransporter; NRP3 (l2fc=−4) that plays a role in modulating intravascular volume and vascular tone; MMP1 (l2fc=−13) involved in the breakdown of extracellular matrix; the expression of many genes responsible for DNA-repair (44/534) and cilium assembly (34/366) was also suppressed. Conclusion Transcriptome analysis shows immunological and non-immunological alterations in HF skeletal muscles and provides the information about molecular mechanisms of its development. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Russian Science Foundation grant

scholarly journals Exercise Training Protects against Atorvastatin-Induced Skeletal Muscle Dysfunction and Mitochondrial Dysfunction in the Skeletal Muscle of Rats

2020 ◽  
Vol 9 (7) ◽  
pp. 2292
Author(s):  
Dae Yun Seo ◽  
Jun-Won Heo ◽  
Mi-Hyun No ◽  
Su-Zi Yoo ◽  
Jeong Rim Ko ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Mitochondrial Dysfunction ◽  
Skeletal Muscles ◽  
The Other ◽  
Aerobic Exercise Training ◽  
Atherosclerotic Cardiovascular Disease ◽  
Ampk Phosphorylation ◽  
Gastrocnemius Muscles ◽  
White Gastrocnemius

Statins are used to prevent and treat atherosclerotic cardiovascular disease, but they also induce myopathy and mitochondrial dysfunction. Here, we investigated whether exercise training prevents glucose intolerance, muscle impairment, and mitochondrial dysfunction in the skeletal muscles of Wistar rats treated with atorvastatin (5 mg kg−1 day−1) for 12 weeks. The rats were assigned to the following three groups: the control (CON), atorvastatin-treated (ATO), and ATO plus aerobic exercise training groups (ATO+EXE). The ATO+EXE group exhibited higher glucose tolerance and forelimb strength and lower creatine kinase levels than the other groups. Mitochondrial respiratory and Ca2+ retention capacity was significantly lower in the ATO group than in the other groups, but exercise training protected against atorvastatin-induced impairment in both the soleus and white gastrocnemius muscles. The mitochondrial H2O2 emission rate was relatively higher in the ATO group and lower in the ATO+EXE group, in both the soleus and white gastrocnemius muscles, than in the CON group. In the soleus muscle, the Bcl-2, SOD1, SOD2, Akt, and AMPK phosphorylation levels were significantly higher in the ATO+EXE group than in the ATO group. In the white gastrocnemius muscle, the SOD2, Akt, and AMPK phosphorylation levels were significantly higher in the ATO+EXE group than in the ATO group. Therefore, exercise training might regulate atorvastatin-induced muscle damage, muscle fatigue, and mitochondrial dysfunction in the skeletal muscles.

scholarly journals Akt1-associated actomyosin remodelling is required for nuclear lamina dispersal and nuclear shrinkage in epidermal terminal differentiation

2021 ◽  
Author(s):  
Clare Rogerson ◽  
Duncan J. Wotherspoon ◽  
Cristina Tommasi ◽  
Robert W. Button ◽  
Ryan F. L. O’Shaughnessy
Keyword(s):  
Actin Filament ◽  
Molecular Mechanisms ◽  
Molecular Motor ◽  
Nuclear Lamina ◽  
Nuclear Volume ◽  
Volume Reduction ◽  
Epidermal Keratinocytes ◽  
Lamin A ◽  
Myosin Iia

AbstractKeratinocyte cornification and epidermal barrier formation are tightly controlled processes, which require complete degradation of intracellular organelles, including removal of keratinocyte nuclei. Keratinocyte nuclear destruction requires Akt1-dependent phosphorylation and degradation of the nuclear lamina protein, Lamin A/C, essential for nuclear integrity. However, the molecular mechanisms that result in complete nuclear removal and their regulation are not well defined. Post-confluent cultures of rat epidermal keratinocytes (REKs) undergo spontaneous and complete differentiation, allowing visualisation and perturbation of the differentiation process in vitro. We demonstrate that there is dispersal of phosphorylated Lamin A/C to structures throughout the cytoplasm in differentiating keratinocytes. We show that the dispersal of phosphorylated Lamin A/C is Akt1-dependent and these structures are specific for the removal of Lamin A/C from the nuclear lamina; nuclear contents and Lamin B were not present in these structures. Immunoprecipitation identified a group of functionally related Akt1 target proteins involved in Lamin A/C dispersal, including actin, which forms cytoskeletal microfilaments, Arp3, required for actin filament nucleation, and Myh9, a component of myosin IIa, a molecular motor that can translocate along actin filaments. Disruption of actin filament polymerisation, nucleation or myosin IIa activity prevented formation and dispersal of cytoplasmic Lamin A/C structures. Live imaging of keratinocytes expressing fluorescently tagged nuclear proteins showed a nuclear volume reduction step taking less than 40 min precedes final nuclear destruction. Preventing Akt1-dependent Lamin A/C phosphorylation and disrupting cytoskeletal Akt1-associated proteins prevented nuclear volume reduction. We propose keratinocyte nuclear destruction and differentiation requires myosin II activity and the actin cytoskeleton for two intermediate processes: Lamin A/C dispersal and rapid nuclear volume reduction.

scholarly journals Requirement for PINCH in Skeletal Myoblast Differentiation

2021 ◽  
Author(s):  
Siyi Xie ◽  
Chushan Fang ◽  
Yujie Gao ◽  
Jie Yan ◽  
Lina Luo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Molecular Mechanisms ◽  
Myogenic Differentiation ◽  
Critical Role ◽  
The Body ◽  
Myoblast Differentiation ◽  
Skeletal Myogenesis ◽  
Congenital Myopathies

Abstract Background: Skeletal muscle is composed of bundles of myofibers ensheathed by extracellular matrix networks. Malformation of skeletal muscle during embryonic development results in congenital myopathies. Disease mechanisms of congenital myopathies remain unclear. PINCH, an adaptor of focal adhesion complex, plays essential roles in multiple cellular processes and organogenesis. Elucidation of the molecular mechanisms underlying skeletal myogenesis will offer new insights into pathogenesis of myopathies.Methods: We generated muscle-specific PINCH knock-out mice to study the functional role of PINCH in skeletal myogenesis. Histologic and Transmission Electron Microscopy analysis demonstrated that Impaired myogenic differentiation and maturation in mice with PINCH1 being ablated in skeletal muscle progenitors, and Ablation of PINCH1 and PINCH2 resulted in reduced size of muscle fibers and impaired multinucleation; Cell culture and immunostaining showed that defects in myoblast fusion and cytoskeleton assembly in PINCH double mutant mice; Western blotting showed that defects in expression of cytoskeleton proteins and proteins involved in myogenesis in DMUT skeletal muscles.Results: Double ablation of PINCH1 and PINCH2 resulted in early postnatal lethality with reduced size of skeletal muscles and detachment of diaphragm muscles from the body wall. Myofibers of PINCH mutant myofibers failed to undergo multinucleation and exhibited disrupted sarcomere structures. The mutant myoblasts in culture were able to adhere to newly formed myotubes, but impeded in cell fusion and subsequent sarcomere genesis and cytoskeleton organization. Consistent with this, expression of integrin β1 and some cytoskeleton proteins, and phosphorylation of ERK and AKT were significantly reduced in PINCH mutants. Expression of MRF4, the most highly expressed myogenic factor at late stages of myogenesis, was abolished in PINCH mutants, that could contribute to observed phenotypes. In addition, mice with PINCH1 being ablated in myogenic progenitors exhibited only mild centronuclear myopathic changes, suggesting a compensatory role of PINCH2 in myogenic differentiation, indicating a critical role of PINCH proteins in myogenic differentiation.Conclusion: Our results demonstrated an essential role of PINCH in skeletal myogenic differentiation.

scholarly journals Metabolomic Profile of Skeletal Muscle and Its Change Under a Mixed-Mode Exercise Intervention in Progressively Dysglycemic Subjects

2021 ◽  
Vol 12 ◽  
Author(s):  
Lukasz Szczerbinski ◽  
Aleksandra Golonko ◽  
Mark Taylor ◽  
Urszula Puchta ◽  
Paulina Konopka ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Mixed Mode ◽  
Skeletal Muscles ◽  
Molecular Mechanisms ◽  
Exercise Intervention ◽  
Metabolic Effects ◽  
Whole Body ◽  
Lipid Species ◽  
Male Patients

Skeletal muscles play an essential role in whole-body glucose homeostasis. They are a key organ system engaged in the development of insulin resistance, and also a crucial tissue mediating the beneficial metabolic effects of physical activity. However, molecular mechanisms underlying both these processes in skeletal muscle remain unclear. The aim of our study was to compare metabolomic profiles in skeletal muscle of patients at different stages of dysglycemia, from normoglycemia through prediabetes to T2D, and its changes under a mixed-mode (strength and endurance) exercise intervention. We performed targeted metabolomics comprising several major metabolite classes, including amino acids, biogenic amines and lipid subgroups in skeletal muscles of male patients. Dysglycemic groups differed significantly at baseline in lysophosphatidylcholines, phosphatidylcholines, sphingomyelins, glutamine, ornithine, and carnosine. Following the exercise intervention, we detected significant changes in lipids and metabolites related to lipid metabolism, including in ceramides and acylcarnitines. With their larger and more significant change over the intervention and among dysglycemic groups, these findings suggest that lipid species may play a predominant role in both the pathogenesis of type 2 diabetes and its protection by exercise. Simultaneously, we demonstrated that amino acid metabolism, especially glutamate dysregulation, is correlated to the development of insulin resistance and parallels disturbances in lipid metabolites.

Measurement of cardiac troponin I in striated muscle using three experimental methods

2003 ◽  
Vol 40 (3) ◽  
pp. 244-248 ◽  
Author(s):  
Salim Fredericks ◽  
Katie Bainbridge ◽  
Joanne F Murray ◽  
Paul O Collinson ◽  
Nicholas D Carter ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Experimental Design ◽  
Cardiac Troponin ◽  
Skeletal Muscles ◽  
Troponin I ◽  
Striated Muscle ◽  
Experimental Methods ◽  
Cardiac Troponin I ◽  
Quantitative Assay ◽  
Qualitative And Quantitative

Background: Qualitative and quantitative measures of cardiac troponin I (cTnI) in striated muscle have been reported as part of diverse investigations. However, there is disparity in the literature regarding the findings of these analyses. The cTnI molecule can exist in phosphorylated, non-phosphorylated, reduced, non-reduced, complexed or non-complexed forms. Each of these forms can change the antigenicity of cTnI, resulting in different antibody-antigen interactions in different experimental formats, thereby giving rise to the disparities in the literature. Methods: cTnI in heart and skeletal muscles were investigated by three techniques employing the same specific cTnI antibodies: the recently revised Dade-Behring Dimension RXL assay, immunoblotting and immunohistochemistry. Results: cTnI was detected in heart muscle but not skeletal muscle using the quantitative assay and immunoblotting. Unexpectedly, using the same antibodies, cTnI was not immunolocalized to either heart or skeletal muscle. Conclusion: The antibody-cTnI interaction might be impeded on fixed immunohistochemistry sections. Our findings reflect those of a previous study, showing that cTnI was not detected in skeletal muscle extracts using a quantitative assay. The behaviour of cTnI antibodies varies depending on experimental design. Conclusions drawn from experiments using qualitative methods cannot necessarily be extrapolated to the quantitative assay and vice versa.

Exercise and muscle dysfunction in COPD: implications for pulmonary rehabilitation

2009 ◽  
Vol 117 (8) ◽  
pp. 281-291 ◽  
Author(s):  
William D.-C. Man ◽  
Paul Kemp ◽  
John Moxham ◽  
Michael I. Polkey
Keyword(s):  
Skeletal Muscle ◽  
Health Status ◽  
Exercise Training ◽  
Pulmonary Rehabilitation ◽  
Skeletal Muscles ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Pharmacological Intervention ◽  
Chronic Obstructive ◽  
Muscle Dysfunction

Skeletal muscle dysfunction in COPD (chronic obstructive pulmonary disease) patients, particularly of the quadriceps, is of clinical interest because it not only influences the symptoms that limit exercise, but may also contribute directly to poor exercise performance and health status, increased healthcare utilization, and mortality. Furthermore, unlike the largely irreversible impairment of the COPD lung, skeletal muscles represent a potential site to improve patients' level of function and quality of life. However, despite expanding knowledge of potential contributing factors and greater understanding of molecular mechanisms of muscle wasting, only one intervention has been shown to be effective in reversing COPD muscle dysfunction, namely exercise training. Pulmonary rehabilitation, an intervention based on individually tailored exercise training, has emerged as arguably the most effective non-pharmacological intervention in improving exercise capacity and health status in COPD patients. The present review describes the effects of chronic exercise training on skeletal muscles and, in particular, focuses on the known effects of pulmonary rehabilitation on the quadriceps muscle in COPD. We also describe the current methods to augment the effects of pulmonary rehabilitation and speculate how greater knowledge of the molecular pathways of skeletal muscle wasting may aid the development of novel pharmaceutical agents.

scholarly journals Transcriptome analysis of skeletal muscles revealed the effect of exercise on the molecular mechanisms regulating muscle growth and metabolism in patients with heart failure

2020 ◽  
Vol 25 (10) ◽  
pp. 4132
Author(s):  
O. A. Ivanova ◽  
E. V. Ignatieva ◽  
T. A. Lelyavina ◽  
V. L. Galenko ◽  
M. Yu. Komarova ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Molecular Mechanisms ◽  
Calcium Release ◽  
Exercise Program ◽  
Rehabilitation Program ◽  
Exercise Intolerance ◽  
Skeletal Muscle Atrophy ◽  
Muscle Membrane

Aim. Heart failure (HF) is accompanied by skeletal muscle atrophy and exercise intolerance. The aim was to study the molecular mechanisms underlying the therapeutic effect of personalized exercise in patients with HF.Material and methods. RNA sequencing obtained from skeletal muscle biopsies before and after a 12-week exercise course was used to identify changes in gene expression and signaling pathways induced by the physical rehabilitation program for patients with HF.Results. We have shown that personalized exercise program in patients with HF stimulates the activation of molecular pathways regulating the differentiation and functioning of skeletal muscles: commitment of muscle progenitor cells; mechanisms regulating the calcium release and sensitivity of myofibrillar contraction, electrical excitability of the muscle membrane, synaptic vesicle proton gradient creation, maintenance of electrochemical gradients of Na+ /K+ . Also, the analysis of differentially expressed genes revealed an increase in the expression of transcription factors MyoD and MEF2, which are responsible for the differentiation of muscle stem cells, and sarcomeric genes MYOM1, MYOM2, MYH7. Along with this, we observed activation of the CYR61 expression — a potential prognostic biomarker for HF patients.Conclusion. Our data show that the beneficial effect of personalized aerobic exercise in patients with HF depends, at least in part, on an improvement in the physiological and biochemical parameters of skeletal muscle.

scholarly journals Akt1-associated actomyosin remodelling is required for nuclear lamina dispersal and nuclear shrinkage in epidermal terminal differentiation

2019 ◽  
Author(s):  
Clare Rogerson ◽  
Duncan Wotherspoon ◽  
Ryan F L O’Shaughnessy
Keyword(s):  
Actin Filament ◽  
Molecular Mechanisms ◽  
Molecular Motor ◽  
Nuclear Lamina ◽  
Nuclear Volume ◽  
Volume Reduction ◽  
Epidermal Keratinocytes ◽  
Lamin A ◽  
Myosin Iia

AbstractKeratinocyte cornification and epidermal barrier formation are tightly controlled processes, which require complete degradation of intracellular organelles, including removal of keratinocyte nuclei. Keratinocyte nuclear destruction requires Akt1-dependent phosphorylation and degradation of the nuclear lamina protein, Lamin A/C, essential for nuclear integrity. However, the molecular mechanisms that result in complete nuclear removal and their regulation are not well defined. Post-confluent cultures of rat epidermal keratinocytes (REKs) undergo spontaneous and complete differentiation, allowing visualisation and perturbation of the differentiation process in vitro. We demonstrate that there is dispersal of phosphorylated Lamin A/C to structures throughout the cytoplasm in differentiating keratinocytes. We show that the dispersal of phosphorylated Lamin A/C is Akt1-dependent and these structures are specific for the removal of Lamin A/C from the nuclear lamina; nuclear contents and Lamin B were not present in these structures. Immunoprecipitation identified a group of functionally related Akt1 target proteins involved in Lamin A/C dispersal, including actin, which forms cytoskeletal microfilaments, Arp3, required for actin filament nucleation, and Myh9, a component of myosin IIa, a molecular motor that can translocate along actin filaments. Disruption of actin filament polymerisation, nucleation or myosin IIa activity prevented formation and dispersal of cytoplasmic Lamin A/C structures. Live imaging of keratinocytes expressing fluorescently tagged nuclear proteins showed a nuclear volume reduction step taking less than 40 minutes precedes final nuclear destruction. Preventing Akt1-dependent Lamin A/C phosphorylation and disrupting cytoskeletal Akt1-associated proteins prevented nuclear volume reduction. Single cell RNA sequencing of differentiating keratinocytes identified gene changes correlated with lamin dispersal, which we propose are due to changes in lamina-associated domains upon Lamin A/C dispersal. We propose keratinocyte nuclear destruction and differentiation requires myosin II activity and the actin cytoskeleton for two intermediate processes: Lamin A/C dispersal and rapid nuclear volume reduction.

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