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Fa Yi Xue Za Zhi Dec 2017To study the relationship between myofibril fragmentation index (MFI) of human skeletal muscle and postmortem interval (PMI).
OBJECTIVES
To study the relationship between myofibril fragmentation index (MFI) of human skeletal muscle and postmortem interval (PMI).
METHODS
The protein concentrations of human right biceps brachii muscle and right quadriceps femoris muscle were obtained at different PMI, and detected at room temperature by biuret method. The MFI of skeletal muscle at 540 nm was measured by ultraviolet spectrophotometer. Regression analysis was performed with time of death as independent variable () and MFI as dependent variable ().
RESULTS
In early PMI, the MFI of human skeletal muscle increased obviously according to the prolongation of PMI, and peaking by 12 h and then tended to steady. Within 12 h after death, the regression equations of right biceps brachii muscle and right quadriceps femoris muscle were =32.660+3.227 (=0.987 9) and =32.380+3.495 (=0.983 9), respectively.
CONCLUSIONS
There's high correlation between MFI and PMI. Combining with forensic practice, MFI can be used for the estimation of early PMI (especially in 12 h).
Topics: Autopsy; Death; Forensic Pathology; Humans; Muscle, Skeletal; Myofibrils; Postmortem Changes; Proteins; Regression Analysis; Spectrophotometry
PubMed: 29441764
DOI: 10.3969/j.issn.1004-5619.2017.06.004 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2018The formation of myofibrils was analyzed in neonatal mouse cardiomyocytes grown in culture and stained with fluorescent antibodies directed against myofibrillar...
The formation of myofibrils was analyzed in neonatal mouse cardiomyocytes grown in culture and stained with fluorescent antibodies directed against myofibrillar proteins. The cardiomyocyte cultures also were exposed to siRNA probes to test the role of nonmuscle myosin IIB expression in the formation of myofibrils. In culture, new myofibrils formed in the spreading cell margins surrounding contractile myofibrils previously assembled in utero. Observations indicated that assembly of mature myofibrils occurred in three-stages, as previously reported in cultured mouse skeletal muscle. Premyofibrils, characterized by minisarcomeres with nonmuscle myosin IIB and muscle-specific alpha-actinin bound to actin filaments, formed in the first stage; followed by nascent myofibrils, the second stage when muscle myosin II and titin were first detected. In the mature myofibril stage muscle myosin II filaments aligned in periodic A-Bands; late assembling proteins, including myomesin and telethonin, were integrated in the sarcomeres, and nonmuscle IIB was absent from the sarcomeres. Treatment of the cultured neonatal cardiomyocytes with gene-specific siRNAs for nonmuscle myosin IIB, led to a marked decrease in the formation of premyofibrils, and subsequently of mature myofibrils. Anat Rec, 301:2067-2079, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Actins; Animals; Animals, Newborn; Cell Differentiation; Cells, Cultured; Mice; Myocytes, Cardiac; Myofibrils
PubMed: 30537042
DOI: 10.1002/ar.23961 -
Journal of Cell Science Jul 2023Myofibrils are long intracellular cables specific to muscles, composed mainly of actin and myosin filaments. The actin and myosin filaments are organized into repeated...
Myofibrils are long intracellular cables specific to muscles, composed mainly of actin and myosin filaments. The actin and myosin filaments are organized into repeated units called sarcomeres, which form the myofibrils. Muscle contraction is achieved by the simultaneous shortening of sarcomeres, which requires all sarcomeres to be the same size. Muscles have a variety of ways to ensure sarcomere homogeneity. We have previously shown that the controlled oligomerization of Zasp proteins sets the diameter of the myofibril. Here, we looked for Zasp-binding proteins at the Z-disc to identify additional proteins coordinating myofibril growth and assembly. We found that the E1 subunit of the oxoglutarate dehydrogenase complex localizes to both the Z-disc and the mitochondria, and is recruited to the Z-disc by Zasp52. The three subunits of the oxoglutarate dehydrogenase complex are required for myofibril formation. Using super-resolution microscopy, we revealed the overall organization of the complex at the Z-disc. Metabolomics identified an amino acid imbalance affecting protein synthesis as a possible cause of myofibril defects, which is supported by OGDH-dependent localization of ribosomes at the Z-disc.
Topics: Animals; Myofibrils; Sarcomeres; Drosophila; Actins; Myosins; Ketoglutarate Dehydrogenase Complex
PubMed: 37272588
DOI: 10.1242/jcs.260717 -
Circulation Research May 2013
Topics: Animals; Cardiomyopathy, Hypertrophic; Female; Humans; Male; Myofibrils; Sarcomeres
PubMed: 23704214
DOI: 10.1161/CIRCRESAHA.113.301406 -
The European Respiratory Journal Dec 2002The pathophysiological mechanisms of weaning from mechanical ventilation are not fully known, but there is accumulating evidence that mechanical ventilation induces... (Review)
Review
The pathophysiological mechanisms of weaning from mechanical ventilation are not fully known, but there is accumulating evidence that mechanical ventilation induces inspiratory muscle dysfunction. Recently, several animal models have provided potential mechanisms for mechanical ventilation-induced effects on muscle function. In patients, weaning difficulties are associated with inspiratory muscle weakness and reduced endurance capacity. Animal studies demonstrated that diaphragm force was already decreased after 12 h of controlled mechanical ventilation and this worsened with time spent on the ventilator. Diaphragmatic myofibril damage observed after 3-days controlled mechanical ventilation was inversely correlated with maximal diaphragmatic force. Downregulation of the diaphragm insulin-like growth factor-I and MyoD/myogenin messenger ribonucleic acid occurred after 24 h and diaphragmatic oxidative stress and increased protease activity after 18 h. In keeping with these findings, diaphragm fibre atrophy was shown after 12 h and reduced diaphragm mass was reported after 48 h of controlled mechanical ventilation. These animal studies show that early alterations in diaphragm function develop after short-term mechanical ventilation. These alterations may contribute to the difficulties in weaning from mechanical ventilation seen in patients. Strategies to preserve respiratory muscle mass and function during mechanical ventilation should be developed. These may include: adaptation of medication, training of the diaphragm, stabilisation of the catabolic state and pharmacotherapy.
Topics: Animals; Diaphragm; Humans; Myofibrils; Respiration, Artificial; Respiratory Muscles; Time Factors; Ventilator Weaning
PubMed: 12503720
DOI: 10.1183/09031936.02.00063102 -
Developmental Biology Jul 2023Slow myosin heavy chain 1 (Smyhc1) is the major sarcomeric myosin driving early contraction by slow skeletal muscle fibres in zebrafish. New mutant alleles lacking a...
Slow myosin heavy chain 1 (Smyhc1) is the major sarcomeric myosin driving early contraction by slow skeletal muscle fibres in zebrafish. New mutant alleles lacking a functional smyhc1 gene move poorly, but recover motility as the later-formed fast muscle fibres of the segmental myotomes mature, and are adult viable. By motility analysis and inhibiting fast muscle contraction pharmacologically, we show that a slow muscle motility defect persists in mutants until about 1 month of age. Breeding onto a genetic background marking slow muscle fibres with EGFP revealed that mutant slow fibres undergo terminal differentiation, migration and fibre formation indistinguishable from wild type but fail to generate large myofibrils and maintain cellular orientation and attachments. In mutants, initial myofibrillar structures with 1.67 μm periodic actin bands fail to mature into the 1.96 μm sarcomeres observed in wild type, despite the presence of alternative myosin heavy chain molecules. The poorly-contractile mutant slow muscle cells generate numerous cytoplasmic organelles, but fail to grow and bundle myofibrils or to increase in cytoplasmic volume despite passive movements imposed by fast muscle. The data show that both slow myofibril maturation and cellular volume increase depend on the function of a specific myosin isoform and suggest that appropriate force production regulates muscle fibre growth.
Topics: Animals; Muscle Contraction; Muscle Fibers, Skeletal; Muscle, Skeletal; Myofibrils; Myosin Heavy Chains; Myosins; Zebrafish
PubMed: 37121308
DOI: 10.1016/j.ydbio.2023.04.002 -
ELife Jan 2021Skeletal muscles are composed of gigantic cells called muscle fibers, packed with force-producing myofibrils. During development, the size of individual muscle fibers...
Skeletal muscles are composed of gigantic cells called muscle fibers, packed with force-producing myofibrils. During development, the size of individual muscle fibers must dramatically enlarge to match with skeletal growth. How muscle growth is coordinated with growth of the contractile apparatus is not understood. Here, we use the large flight muscles to mechanistically decipher how muscle fiber growth is controlled. We find that regulated activity of core members of the Hippo pathway is required to support flight muscle growth. Interestingly, we identify Dlg5 and Slmap as regulators of the STRIPAK phosphatase, which negatively regulates Hippo to enable post-mitotic muscle growth. Mechanistically, we show that the Hippo pathway controls timing and levels of sarcomeric gene expression during development and thus regulates the key components that physically mediate muscle growth. Since Dlg5, STRIPAK and the Hippo pathway are conserved a similar mechanism may contribute to muscle or cardiomyocyte growth in humans.
Topics: Animals; Drosophila melanogaster; Gene Expression Regulation; Hippo Signaling Pathway; Muscle Fibers, Skeletal; Myofibrils; Sarcomeres
PubMed: 33404503
DOI: 10.7554/eLife.63726 -
PLoS Genetics Feb 2022Myofibrils within skeletal muscle are composed of sarcomeres that generate force by contraction when their myosin-rich thick filaments slide past actin-based thin...
Myofibrils within skeletal muscle are composed of sarcomeres that generate force by contraction when their myosin-rich thick filaments slide past actin-based thin filaments. Although mutations in components of the sarcomere are a major cause of human disease, the highly complex process of sarcomere assembly is not fully understood. Current models of thin filament assembly highlight a central role for filament capping proteins, which can be divided into three protein families, each ascribed with separate roles in thin filament assembly. CapZ proteins have been shown to bind the Z-disc protein α-actinin to form an anchoring complex for thin filaments and actin polymerisation. Subsequent thin filaments extension dynamics are thought to be facilitated by Leiomodins (Lmods) and thin filament assembly is concluded by Tropomodulins (Tmods) that specifically cap the pointed end of thin filaments. To study thin filament assembly in vivo, single and compound loss-of-function zebrafish mutants within distinct classes of capping proteins were analysed. The generated lmod3- and capza1b-deficient zebrafish exhibited aspects of the pathology caused by variations in their human orthologs. Although loss of the analysed main capping proteins of the skeletal muscle, capza1b, capza1a, lmod3 and tmod4, resulted in sarcomere defects, residual organised sarcomeres were formed within the assessed mutants, indicating that these proteins are not essential for the initial myofibril assembly. Furthermore, detected similarity and location of myofibril defects, apparent at the peripheral ends of myofibres of both Lmod3- and CapZα-deficient mutants, suggest a function in longitudinal myofibril growth for both proteins, which is molecularly distinct to the function of Tmod4.
Topics: Actins; Animals; CapZ Actin Capping Protein; Microfilament Proteins; Muscle Proteins; Muscular Diseases; Myofibrils; Tropomodulin; Zebrafish
PubMed: 35148320
DOI: 10.1371/journal.pgen.1010066 -
International Journal of Molecular... Dec 2020Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the most prevalent forms of the chronic and progressive pathological condition known as... (Review)
Review
Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the most prevalent forms of the chronic and progressive pathological condition known as cardiomyopathy. These diseases have different aetiologies; however, they share the feature of haemodynamic abnormalities, which is mainly due to dysfunction in the contractile proteins that make up the contractile unit known as the sarcomere. To date, pharmacological treatment options are not disease-specific and rather focus on managing the symptoms, without addressing the disease mechanism. Earliest attempts at improving cardiac contractility by modulating the sarcomere indirectly (inotropes) resulted in unwanted effects. In contrast, targeting the sarcomere directly, aided by high-throughput screening systems, could identify small molecules with a superior therapeutic value in cardiac muscle disorders. Herein, an extensive literature review of 21 small molecules directed to five different targets was conducted. A simple scoring system was created to assess the suitability of small molecules for therapy by evaluating them in eight different criteria. Most of the compounds failed due to lack of target specificity or poor physicochemical properties. Six compounds stood out, showing a potential therapeutic value in HCM, DCM or heart failure (HF). Omecamtiv Mecarbil and Danicamtiv (myosin activators), Mavacamten, CK-274 and MYK-581 (myosin inhibitors) and AMG 594 (Ca-sensitiser) are all small molecules that allosterically modulate troponin or myosin. Omecamtiv Mecarbil showed limited efficacy in phase III GALACTIC-HF trial, while, results from phase III EXPLORER-HCM trial were recently published, indicating that Mavacamten reduced left ventricular outflow tract (LVOT) obstruction and diastolic dysfunction and improved the health status of patients with HCM. A novel category of small molecules known as "recouplers" was reported to target a phenomenon termed uncoupling commonly found in familial cardiomyopathies but has not progressed beyond preclinical work. In conclusion, the contractile apparatus is a promising target for new drug development.
Topics: Animals; Cardiomyopathy, Hypertrophic; Cardiotonic Agents; Clinical Trials as Topic; Humans; Muscle Contraction; Muscular Diseases; Myofibrils
PubMed: 33339418
DOI: 10.3390/ijms21249599 -
Circulation. Heart Failure Jul 2016The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular... (Comparative Study)
Comparative Study
BACKGROUND
The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction.
METHODS AND RESULTS
By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction.
CONCLUSIONS
RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness.
Topics: Animals; Arterial Pressure; Collagen Type I; Collagen Type III; Connectin; Constriction; Cyclic AMP-Dependent Protein Kinases; Disease Models, Animal; Elasticity; Fibrosis; Hypertension, Pulmonary; Male; Myocardium; Myofibrils; Phosphorylation; Pulmonary Artery; Rats, Wistar; Severity of Illness Index; Time Factors; Ventricular Dysfunction, Right; Ventricular Function, Right
PubMed: 27370069
DOI: 10.1161/CIRCHEARTFAILURE.115.002636