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1.
Elife ; 102021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569933

RESUMO

Regulated thin filaments (RTFs) tightly control striated muscle contraction through calcium binding to troponin, which enables tropomyosin to expose myosin-binding sites on actin. Myosin binding holds tropomyosin in an open position, exposing more myosin-binding sites on actin, leading to cooperative activation. At lower calcium levels, troponin and tropomyosin turn off the thin filament; however, this is antagonised by the high local concentration of myosin, questioning how the thin filament relaxes. To provide molecular details of deactivation, we used single-molecule imaging of green fluorescent protein (GFP)-tagged myosin-S1 (S1-GFP) to follow the activation of RTF tightropes. In sub-maximal activation conditions, RTFs are not fully active, enabling direct observation of deactivation in real time. We observed that myosin binding occurs in a stochastic step-wise fashion; however, an unexpectedly large probability of multiple contemporaneous detachments is observed. This suggests that deactivation of the thin filament is a coordinated active process.


Assuntos
Citoesqueleto de Actina/metabolismo , Miosinas/metabolismo , Imagem Individual de Molécula/métodos , Proteínas de Fluorescência Verde/metabolismo , Humanos , Músculo Estriado/metabolismo , Ligação Proteica , Processos Estocásticos , Troponina/metabolismo
2.
Sci Rep ; 11(1): 16705, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408190

RESUMO

This study presents the detailed anatomy of the Cowper's gland in humans. Elucidating the mechanism of secretion and emission of the Cowper's gland requires analysis of the muscles around the Cowper's gland. We hypothesized that the Cowper's gland involves not only smooth muscle but also the striated muscles of the pelvic floor. Here, we provide comprehensive and three-dimensional anatomy of the Cowper's gland and its surrounding structures, which overcomes the current local and planar understanding. In this study, seven male corpses of body donors were used to conduct macroscopic anatomy, histology, and three-dimensional reconstruction. The Cowper's gland was surrounded laterally and posterosuperiorly by striated and smooth muscles, respectively. The striated muscle bundle was connected from the superficial transverse perineal muscle, levator ani, and external anal sphincter to the external urethral sphincter (rhabdosphincter). The smooth muscle was part of the deep transverse perineal muscle and entered between the bilateral Cowper's glands and lobules. Our findings indicate that the secretion and emission of the Cowper's gland in humans are carried out through the cooperation of striated and smooth muscles.


Assuntos
Glândulas Bulbouretrais/anatomia & histologia , Músculo Liso/anatomia & histologia , Músculo Estriado/anatomia & histologia , Uretra/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Glândulas Bulbouretrais/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso/fisiologia , Músculo Estriado/fisiologia , Uretra/fisiologia
3.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360941

RESUMO

Phospholipids (PLs) are amphiphilic molecules that were essential for life to become cellular. PLs have not only a key role in compartmentation as they are the main components of membrane, but they are also involved in cell signaling, cell metabolism, and even cell pathophysiology. Considered for a long time to simply be structural elements of membranes, phospholipids are increasingly being viewed as sensors of their environment and regulators of many metabolic processes. After presenting their main characteristics, we expose the increasing methods of PL detection and identification that help to understand their key role in life processes. Interest and importance of PL homeostasis is growing as pathogenic variants in genes involved in PL biosynthesis and/or remodeling are linked to human diseases. We here review diseases that involve deregulation of PL homeostasis and present a predominantly muscular phenotype.


Assuntos
Músculo Estriado/metabolismo , Fosfolipídeos/metabolismo , Animais , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Humanos , Mitocôndrias/metabolismo , Músculo Estriado/fisiologia , Fosfolipídeos/química
4.
Nat Commun ; 12(1): 4086, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215727

RESUMO

Sarcomeres, the basic contractile units of striated muscle, produce the forces driving muscular contraction through cross-bridge interactions between actin-containing thin filaments and myosin II-based thick filaments. Until now, direct visualization of the molecular architecture underlying sarcomere contractility has remained elusive. Here, we use in situ cryo-electron tomography to unveil sarcomere contraction in frozen-hydrated neonatal rat cardiomyocytes. We show that the hexagonal lattice of the thick filaments is already established at the neonatal stage, with an excess of thin filaments outside the trigonal positions. Structural assessment of actin polarity by subtomogram averaging reveals that thin filaments in the fully activated state form overlapping arrays of opposite polarity in the center of the sarcomere. Our approach provides direct evidence for thin filament sliding during muscle contraction and may serve as a basis for structural understanding of thin filament activation and actomyosin interactions inside unperturbed cellular environments.


Assuntos
Actinas/metabolismo , Contração Muscular/fisiologia , Miócitos Cardíacos/fisiologia , Sarcômeros/fisiologia , Citoesqueleto de Actina , Animais , Masculino , Camundongos Endogâmicos C57BL , Músculo Esquelético/química , Músculo Estriado , Miócitos Cardíacos/ultraestrutura , Miofibrilas , Ratos , Ratos Wistar , Sarcômeros/ultraestrutura
5.
Biomolecules ; 11(6)2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204548

RESUMO

Endothelial lipase (EL) is an enzyme capable of HDL phospholipids hydrolysis. Its action leads to a reduction in the serum high-density lipoprotein concentration, and thus, it exerts a pro-atherogenic effect. This study examines the impact of a single bout exercise on the gene and protein expression of the EL in skeletal muscles composed of different fiber types (the soleus-mainly type I, the red gastrocnemius-mostly IIA, and the white gastrocnemius-predominantly IIX fibers), as well as the diaphragm, and the heart. Wistar rats were subjected to a treadmill run: (1) t = 30 [min], V = 18 [m/min]; (2) t = 30 [min], V = 28 [m/min]; (3) t = 120 [min], V = 18 [m/min] (designated: M30, F30, and M120, respectively). We established EL expression in the total muscle homogenates in sedentary animals. Resting values could be ordered with the decreasing EL protein expression as follows: endothelium of left ventricle > diaphragm > red gastrocnemius > right ventricle > soleus > white gastrocnemius. Furthermore, we observed that even a single bout of exercise was capable of inducing changes in the mRNA and protein level of EL, with a clearer pattern observed for the former. After 30 min of running at either exercise intensity, the expression of EL transcript in all the cardiovascular components of muscles tested, except the soleus, was reduced in comparison to the respective sedentary control. The protein content of EL varied with the intensity and/or duration of the run in the studied whole tissue homogenates. The observed differences between EL expression in vascular beds of muscles may indicate the muscle-specific role of the lipase.


Assuntos
Endotélio Vascular/enzimologia , Regulação da Expressão Gênica , Lipase/biossíntese , Músculo Estriado/enzimologia , Condicionamento Físico Animal , Corrida , Animais , Masculino , Ratos , Ratos Wistar
6.
Parasit Vectors ; 14(1): 223, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33892779

RESUMO

BACKGROUND: Cattle are intermediate hosts of six Sarcocystis species, among which Sarcocystis hominis and Sarcocystis heydorni can infect humans through the consumption of raw or undercooked meat. In addition to the zoonotic potential, there is increasing interest in these protozoa because of the evidence supporting the role of Sarcocystis spp. in the occurrence of bovine eosinophilic myositis (BEM), a specific inflammatory myopathy which leads to carcass condemnation and considerable economic losses. Actually, all the prevalence studies carried out on cattle in Italy have been based on either morphological or 18S rDNA-based molecular techniques, most likely leading to misidentification of closely related species. Therefore, there is a strong need for new data on the prevalence of the different Sarcocystis spp. in cattle in Italy and their association with bovine eosinophilic myositis. METHODS: To reach our aim, individual striated muscle samples from BEM condemned carcasses (N = 54) and diaphragm muscle samples from randomly sampled carcasses (N = 59) were obtained from Northwest Italy slaughterhouses. Genomic DNA was extracted and analyzed by multiplex-PCR targeting 18S rDNA and cox1 genes. PCR products amplified using the genus-specific primer set in absence of the specific fragment for S. hirsuta, S. cruzi, S. hominis or S. bovifelis were sequenced to achieve species identification. RESULTS: Sarcocystis DNA was detected in 67.8% of the samples from slaughter cattle and in 90.7% of the samples from BEM condemned carcasses. S. cruzi was identified as the most prevalent species in slaughter cattle (61%), followed by S. bovifelis (10.2%), S. hominis (8.5%) and S. hirsuta (1.7%). Notably, among the different Sarcocystis spp. detected, the presence of S. bovifelis and S. hominis was significantly higher in samples isolated from BEM condemned carcasses (46.3% and 40.7% respectively), while there was no statistically significant difference between the presence of S. cruzi or S. hirsuta in BEM condemned carcasses (42.6% and 1.8%, respectively) and randomly sampled carcasses. Furthermore, DNA sequence analysis revealed the presence of a putative new species in two carcasses. CONCLUSIONS: Our study contributes to updating the data on the prevalence of the different Sarcocystis spp. in cattle in Italy, highlighting the presence of three Sarcocystis spp., S. cruzi, S. hominis and S. bovifelis, in BEM lesions and allowing us to speculate on the possible role of S. hominis and S. bovifelis as the major sarcosporidian species involved in bovine eosinophilic myositis.


Assuntos
Doenças dos Bovinos/parasitologia , Distrofia Muscular do Cíngulo dos Membros/parasitologia , Sarcocystis/isolamento & purificação , Sarcocistose/veterinária , Animais , Bovinos , DNA de Protozoário/análise , Itália/epidemiologia , Músculo Estriado/parasitologia , Filogenia , Prevalência , Sarcocystis/classificação , Sarcocistose/epidemiologia
7.
Indian J Pathol Microbiol ; 64(2): 382-384, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33851641

RESUMO

Rhabdomyolysis is a potentially life-threatening clinical syndrome characterized by the breakdown of skeletal muscle cells and release of creatine kinase (CK), lactate dehydrogenase (LDH), and myoglobin into the plasma and interstitial space. Rhabdomyolysis can occur due to a variety of causes and acute kidney injury (AKI) is one of its most dreaded complications occurring in 33%-50% patients. The main pathophysiology of renal injury is due to vasoconstriction, intraluminal casts, tubular obstruction, and direct myoglobin toxicity. As the symptoms are nonspecific, a high level of suspicion is required in the mind of the treating physician. Early diagnosis and prompt management with fluid resuscitation, initiation of renal replacement therapy (RRT), and elimination of causative agents can help prevent complications. We hereby report four interesting cases of this clinical syndrome with emphasis on the causative agents.


Assuntos
Injúria Renal Aguda/patologia , Mioglobina/sangue , Rabdomiólise/diagnóstico , Rabdomiólise/patologia , Injúria Renal Aguda/terapia , Adulto , Creatina Quinase/sangue , Feminino , Humanos , Rim/patologia , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Músculo Estriado/patologia , Terapia de Substituição Renal/métodos , Rabdomiólise/terapia , Adulto Jovem
9.
J Gen Physiol ; 153(7)2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33740038

RESUMO

Microtubules tune cytoskeletal stiffness, which affects cytoskeletal mechanics and mechanotransduction of striated muscle. While recent evidence suggests that microtubules enriched in detyrosinated α-tubulin regulate these processes in healthy muscle and increase them in disease, the possible contribution from several other α-tubulin modifications has not been investigated. Here, we used genetic and pharmacologic strategies in isolated cardiomyocytes and skeletal myofibers to increase the level of acetylated α-tubulin without altering the level of detyrosinated α-tubulin. We show that microtubules enriched in acetylated α-tubulin increase cytoskeletal stiffness and viscoelastic resistance. These changes slow rates of contraction and relaxation during unloaded contraction and increased activation of NADPH oxidase 2 (Nox2) by mechanotransduction. Together, these findings add to growing evidence that microtubules contribute to the mechanobiology of striated muscle in health and disease.


Assuntos
Músculo Estriado , Tubulina (Proteína) , Acetilação , Mecanotransdução Celular , Microtúbulos/metabolismo , Músculo Estriado/metabolismo , Tubulina (Proteína)/metabolismo , Tirosina/metabolismo
10.
Int J Biol Macromol ; 179: 388-397, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33689771

RESUMO

Pacific oyster (Crassostrea gigas), the most productive economical bivalve mollusc, is identified as an attractive model for developmental studies due to its classical mosaic developmental pattern. Myosin heavy chain is a structural and functional component of myosin, the key muscle protein of thick filament. Here, full length cDNA of striated myosin heavy chains in C. gigas (CgSmhc) was obtained, and the expression profiles were examined in different development stage. CgSmhc had a high expression level in trochophore and D-shaped stage during embryo-larval stage. In adult, CgSmhc was a muscle-specific gene and primarily expressed in muscle tissues. Then, activity of 5' flanking region of CgSmhc were examined through an reconstructed EGFP vector. The results indicated that 3098 bp 5'-flanking region of CgSmhc owned various conserved binding sites of myogenesis-related regulatory elements, and the 2000 bp 5'-flanking sequence was sufficient to induce the CgSmhc expression. Subsequently, the CRISPR/Cas9-mediated target disruption of CgSmhc was generated by co-injection of Cas9mRNA and CgSmhc-sgRNAs into one-cell stage embryos of C. gigas. Loss of CgSmhc had a visible effect on the sarcomeric organization of thin filaments in larval musculature, indicating that CgSmhc was required during larval myogenesis to regulate the correct assembly of sarcomere.


Assuntos
Crassostrea , Desenvolvimento Muscular , Músculo Estriado/crescimento & desenvolvimento , Cadeias Pesadas de Miosina/fisiologia , Animais , Crassostrea/crescimento & desenvolvimento , Expressão Gênica , Larva/crescimento & desenvolvimento
11.
Physiol Rev ; 101(4): 1561-1607, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33733879

RESUMO

The design of the energy metabolism system in striated muscle remains a major area of investigation. Here, we review our current understanding and emerging hypotheses regarding the metabolic support of muscle contraction. Maintenance of ATP free energy, so called energy homeostasis, via mitochondrial oxidative phosphorylation is critical to sustained contractile activity, and this major design criterion is the focus of this review. Cell volume invested in mitochondria reduces the space available for generating contractile force, and this spatial balance between mitochondria acontractile elements to meet the varying sustained power demands across muscle types is another important design criterion. This is accomplished with remarkably similar mass-specific mitochondrial protein composition across muscle types, implying that it is the organization of mitochondria within the muscle cell that is critical to supporting sustained muscle function. Beyond the production of ATP, ubiquitous distribution of ATPases throughout the muscle requires rapid distribution of potential energy across these large cells. Distribution of potential energy has long been thought to occur primarily through facilitated metabolite diffusion, but recent analysis has questioned the importance of this process under normal physiological conditions. Recent structural and functional studies have supported the hypothesis that the mitochondrial reticulum provides a rapid energy distribution system via the conduction of the mitochondrial membrane potential to maintain metabolic homeostasis during contractile activity. We extensively review this aspect of the energy metabolism design contrasting it with metabolite diffusion models and how mitochondrial structure can play a role in the delivery of energy in the striated muscle.


Assuntos
Metabolismo Energético/fisiologia , Músculo Estriado/metabolismo , Animais , Humanos , Mitocôndrias Musculares/metabolismo , Mitocôndrias Musculares/fisiologia , Células Musculares/metabolismo
12.
J Biol Chem ; 296: 100395, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33567340

RESUMO

Chronic glucocorticoid exposure causes insulin resistance and muscle atrophy in skeletal muscle. We previously identified phosphoinositide-3-kinase regulatory subunit 1 (Pik3r1) as a primary target gene of skeletal muscle glucocorticoid receptors involved in the glucocorticoid-mediated suppression of insulin action. However, the in vivo functions of Pik3r1 remain unclear. Here, we generated striated muscle-specific Pik3r1 knockout (MKO) mice and treated them with a dexamethasone (DEX), a synthetic glucocorticoid. Treating wildtype (WT) mice with DEX attenuated insulin activated Akt activity in liver, epididymal white adipose tissue, and gastrocnemius (GA) muscle. This DEX effect was diminished in GA muscle of MKO mice, therefore, resulting in improved glucose and insulin tolerance in DEX-treated MKO mice. Stable isotope labeling techniques revealed that in WT mice, DEX treatment decreased protein fractional synthesis rates in GA muscle. Furthermore, histology showed that in WT mice, DEX treatment reduced GA myotube diameters. In MKO mice, myotube diameters were smaller than in WT mice, and there were more fast oxidative fibers. Importantly, DEX failed to further reduce myotube diameters. Pik3r1 knockout also decreased basal protein synthesis rate (likely caused by lower 4E-BP1 phosphorylation at Thr37/Thr46) and curbed the ability of DEX to attenuate protein synthesis rate. Finally, the ability of DEX to inhibit eIF2α phosphorylation and insulin-induced 4E-BP1 phosphorylation was reduced in MKO mice. Taken together, these results demonstrate the role of Pik3r1 in glucocorticoid-mediated effects on glucose and protein metabolism in skeletal muscle.


Assuntos
Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo , Glucocorticoides/farmacologia , Glucose/metabolismo , Resistência à Insulina , Músculo Estriado/efeitos dos fármacos , Músculo Estriado/metabolismo , Atrofia Muscular/metabolismo , Animais , Classe Ia de Fosfatidilinositol 3-Quinase/genética , Modelos Animais de Doenças , Insulina/metabolismo , Masculino , Camundongos , Camundongos Knockout , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Músculo Estriado/patologia , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
13.
J Cell Sci ; 134(6)2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33536248

RESUMO

The LMNA gene encodes the A-type lamins, which polymerize into ∼3.5-nm-thick filaments and, together with B-type lamins and associated proteins, form the nuclear lamina. Mutations in LMNA cause a wide variety of pathologies. In this study, we analyzed the nuclear lamina of embryonic fibroblasts from Lmna H222P/H222P mice, which develop cardiomyopathy and muscular dystrophy. Although the organization of the lamina appeared unaltered, there were changes in chromatin and B-type lamin expression. An increase in nuclear size and consequently a relative reduction in heterochromatin near the lamina allowed for a higher resolution structural analysis of lamin filaments using cryo-electron tomography. This was most apparent when visualizing lamin filaments in situ and using a nuclear extraction protocol. Averaging of individual segments of filaments in Lmna H222P/H222P mouse fibroblasts resolved two polymers that constitute the mature filaments. Our findings provide better views of the organization of lamin filaments and the effect of a striated muscle disease-causing mutation on nuclear structure.


Assuntos
Lamina Tipo A , Músculo Estriado , Animais , Citoesqueleto , Lamina Tipo A/genética , Lamina Tipo B/genética , Camundongos , Mutação/genética , Lâmina Nuclear
14.
Low Urin Tract Symptoms ; 13(2): 308-318, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33098273

RESUMO

OBJECTIVES: Based on the recent advancements in cell therapy techniques, we aimed to evaluate the efficacy of transurethral injection of autologous adipose-derived stem cells, muscle-derived stem cells, and co-cultured cells for the rehabilitation of stress urinary incontinence rat models. We hypothesized that the utilization of co-cultured stem cells could result in enhanced therapeutic outcomes attributed to their more comprehensive environment of paracrine factors and cytokines. METHODS: We performed bilateral pudendal nerve transection surgeries to simulate urinary incontinence in 25 female Wistar rats and employed urodynamic evaluations to confirm the injury. We autologously isolated and cultured adipose-derived mesenchymal stem cells, muscle-derived stem cells, and a mixed culture of the two types, which we subsequently injected into the urethral lumen of the damaged animals. Three weeks after the injection, urodynamic assays, histological staining, and immunohistochemical evaluations were performed to determine the efficacy of the implanted cell cultures in sphincter function improvements or structural modifications. RESULTS: Histological evaluations suggested a regenerative process in the muscular layer of the external sphincter 3 weeks after the injection. Also, immunohistochemical analysis revealed a thickened periurethral striated muscle layer in the co-cultured group. Postinjection urodynamic analysis indicated that the urethral pressure profile significantly increased in the co-cultured group compared with other groups. CONCLUSIONS: The outcomes of this investigation indicated that the application of co-cultured adipose-derived and muscle-derived stem cells could be associated with higher therapeutic value in stress urinary incontinence patients compared with singular-cell treatments.


Assuntos
Músculo Estriado , Incontinência Urinária por Estresse , Tecido Adiposo , Animais , Feminino , Humanos , Ratos , Ratos Wistar , Células-Tronco , Incontinência Urinária por Estresse/cirurgia
16.
Biophys J ; 120(1): 1-9, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33221250

RESUMO

Recently, our understanding of the structural basis of troponin-tropomyosin's Ca2+-triggered regulation of striated muscle contraction has advanced greatly, particularly via cryo-electron microscopy data. Compelling atomic models of troponin-tropomyosin-actin were published for both apo- and Ca2+-saturated states of the cardiac thin filament. Subsequent electron microscopy and computational analyses have supported and further elaborated the findings. Per cryo-electron microscopy, each troponin is highly extended and contacts both tropomyosin strands, which lie on opposite sides of the actin filament. In the apo-state characteristic of relaxed muscle, troponin and tropomyosin hinder strong myosin-actin binding in several different ways, apparently barricading the actin more substantially than does tropomyosin alone. The troponin core domain, the C-terminal third of TnI, and tropomyosin under the influence of a 64-residue helix of TnT located at the overlap of adjacent tropomyosins are all in positions that would hinder strong myosin binding to actin. In the Ca2+-saturated state, the TnI C-terminus dissociates from actin and binds in part to TnC; the core domain pivots significantly; the N-lobe of TnC binds specifically to actin and tropomyosin; and tropomyosin rotates partially away from myosin's binding site on actin. At the overlap domain, Ca2+ causes much less tropomyosin movement, so a more inhibitory orientation persists. In the myosin-saturated state of the thin filament, there is a large additional shift in tropomyosin, with molecular interactions now identified between tropomyosin and both actin and myosin. A new era has arrived for investigation of the thin filament and for functional understandings that increasingly accommodate the recent structural results.


Assuntos
Cálcio , Músculo Estriado , Troponina , Citoesqueleto de Actina , Actinas , Microscopia Crioeletrônica , Modelos Moleculares , Contração Muscular , Tropomiosina
17.
Exp Cell Res ; 398(1): 112388, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33221314

RESUMO

Previous work with cultured cells has shown transcription of muscle genes by serum response factor (SRF) can be stimulated by actin polymerization driven by proteins of the formin family. However, it is not clear if endogenous formins similarly promote SRF-dependent transcription during muscle development in vivo. We tested whether formin activity promotes SRF-dependent transcription in striated muscle in the simple animal model, Caenorhabditis elegans. Our lab has shown FHOD-1 is the only formin that directly promotes sarcomere formation in the worm's striated muscle. We show here FHOD-1 and SRF homolog UNC-120 both support muscle growth and also muscle myosin II heavy chain A expression. However, while a hypomorphic unc-120 allele blunts expression of a set of striated muscle genes, these genes are largely upregulated or unchanged by absence of FHOD-1. Instead, pharmacological inhibition of the proteasome restores myosin protein levels in worms lacking FHOD-1, suggesting elevated proteolysis accounts for their myosin deficit. Interestingly, proteasome inhibition does not restore normal muscle growth to fhod-1(Δ) mutants, suggesting formin contributes to muscle growth by some alternative mechanism. Overall, we find SRF does not depend on formin to promote muscle gene transcription in a simple in vivo system.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Forminas/metabolismo , Músculo Estriado/metabolismo , Fator de Resposta Sérica/metabolismo , Animais , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proliferação de Células , Forminas/genética , Fator de Resposta Sérica/genética
18.
Ann Anat ; 234: 151647, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33221387

RESUMO

INTRODUCTION: The superficial musculoaponeurotic system (SMAS) is a controversial functional fibro-adipose layer that connects the mimic muscles to the skin and is involved in a variety of facial mimic expressions. The presence of muscle fibers within SMAS fibrous septa is hypothetical. The present study analyzed SMAS fibrous septa composition for the existence of striated muscle cells. METHODS: Histological serial sections of the sample borders (n=107) of 19 in sano-resected and diagnosed cutaneous tumors of the midfacial region were investigated. Immunohistochemical (actin and myosin) and hematoxylin and eosin staining were performed to detect striated muscle cells in SMAS fibrous septa. RESULTS: A fibro-neuro-musculo-vascular functional unit within SMAS fibrous septa was demonstrated. SMAS striated muscle cells were morphologically independent from preparotideal and periorbital mimic muscles. Intraseptal blood vessels draining the superficial and deep SMAS vascular system were described. CONCLUSIONS: Striated muscle cells were demonstrated within SMAS fibrous septa. Nerve cells and vascular tissue together with the SMAS fibro-muscular meshwork demonstrated an autonomous operating functional unit that hypothetical modulated individual mimic expression contributing to the diversity of mimic expression. The SMAS develops with mimic muscle contractions as a synergetic effect during facial crease and fold formation processes.


Assuntos
Músculo Estriado , Sistema Musculoaponeurótico Superficial , Tecido Adiposo , Face , Músculos Faciais
19.
J Gen Physiol ; 153(3)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33275758

RESUMO

Myosin-binding protein C (MyBP-C) is a critical regulator of muscle performance that was first identified through its strong binding interactions with myosin, the force-generating protein of muscle. Almost simultaneously with its discovery, MyBP-C was soon found to bind to actin, the physiological catalyst for myosin's activity. However, the two observations posed an apparent paradox, in part because interactions of MyBP-C with myosin were on the thick filament, whereas MyBP-C interactions with actin were on the thin filament. Despite the intervening decades since these initial discoveries, it is only recently that the dual binding modes of MyBP-C are becoming reconciled in models that place MyBP-C at a central position between actin and myosin, where MyBP-C alternately stabilizes a newly discovered super-relaxed state (SRX) of myosin on thick filaments in resting muscle and then prolongs the "on" state of actin on thin filaments in active muscle. Recognition of these dual, alternating functions of MyBP-C reveals how it is central to the regulation of both muscle contraction and relaxation. The purpose of this Viewpoint is to briefly summarize the roles of MyBP-C in binding to myosin and actin and then to highlight a possible new role for MyBP-C in inducing and damping oscillatory waves of contraction and relaxation. Because the contractile waves bear similarity to cycles of contraction and relaxation in insect flight muscles, which evolved for fast, energetically efficient contraction, the ability of MyBP-C to damp so-called spontaneous oscillatory contractions (SPOCs) has broad implications for previously unrecognized regulatory mechanisms in vertebrate striated muscle. While the molecular mechanisms by which MyBP-C can function as a wave maker or a wave breaker are just beginning to be explored, it is likely that MyBP-C dual interactions with both myosin and actin will continue to be important for understanding the new functions of this enigmatic protein.


Assuntos
Proteínas de Transporte , Músculo Estriado , Animais , Músculo Estriado/metabolismo , Miosinas/metabolismo , Vertebrados/metabolismo
20.
J Cutan Pathol ; 48(2): 237-246, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32804407

RESUMO

Smooth muscle hamartoma (SMH) and striated muscle hamartoma (STH) are anomalous proliferations of smooth muscle or striated muscle, respectively, in anatomic sites where these tissues are normally present. To date, only limited cases have been reported describing these lesions. In this study, we sought to characterize the clinicopathologic features of both SMH and STH. A total of 27 cases of SMH and 12 cases of STH from 1990 to 2020 were identified. SMH cases had a slight male predominance (63%) and a mean age of presentation of 20 years (range: 4 months-91 years), with a mean size of 9.3 mm (±13.3). In contrast, STH were equally distributed in gender, with a mean age of presentation of 40 years (range: 3 months-66 years) and a mean size of 5.7 mm (±3.6). SMH were more commonly located in the torso and extremities (70%) and STH in the head and neck area (92%). One case of SMH recurred after 1.1 years and in the initial diagnosis the lesion was present at the tissue edge. None of the cases of STH had a recurrence. We present the largest cohort of SMH and STH, and report the first case of a recurrent SMH, suggesting the importance of obtaining a clean margin for these lesions.


Assuntos
Hamartoma , Neoplasias de Cabeça e Pescoço , Neoplasias Musculares , Músculo Liso , Músculo Estriado , Adolescente , Adulto , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Hamartoma/metabolismo , Hamartoma/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Lactente , Masculino , Neoplasias Musculares/metabolismo , Neoplasias Musculares/patologia , Músculo Liso/metabolismo , Músculo Liso/patologia , Músculo Estriado/metabolismo , Músculo Estriado/patologia
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