Disease relevance of Myofibrils

• CONCLUSIONS: Calcium sensitization affects function and mechanical efficiency of stunned myocardium more profoundly than of not-stunned myocardium, lending support to the hypothesis that Ca2+ desensitization of the myofibrils is involved in myocardial stunning [1].
• A full-thickness wedge biopsy was performed, and hematoxylin and eosin staining and immunohistochemistry analysis of the specimen demonstrated normal myofibrils but a severely destructive monocytic fasciitis [2].
• Human wild-type cardiac troponin T, I, C and five troponin T mutants (I79N, R92Q, F110I, E244D, and R278C) causing familial hypertrophic cardiomyopathy were expressed in Escherichia coli, and then were purified and incorporated into rabbit cardiac myofibrils using a troponin exchange technique [3].
• Cardiac hypertrophy, however, may also show alterations affecting capillary luminal volume and surface and the mitochondrial to myofibril volume ratio, which indicate an inadequate growth adaptation of the component structures responsible for tissue oxygenation and energy production [4].
• The switch to supply of energy by diffusion of MgATP into the myofibril when depletion of PCr raises [ATP]/[PCr] greatly, e.g. during anoxia, results in a local [Mg2+] increase, which inhibits the ATPase [5].

Psychiatry related information on Myofibrils

• Cardiac myofibril disorientation and Z band abnormalities in idiopathic cardiomyopathy. An electron microscope study [6].

High impact information on Myofibrils

• Consequently, mutations in C. elegans unc-45 result in paralyzed animals with severe myofibril disorganization in striated body wall muscles [7].
• Electron microscopic analysis of the heart revealed disorganization of myofibrils and disruption of Z-disks [8].
• Arthrin formation lags several hours behind that of actin III, implying that ubiquitination coincides with some aspect of myofibril assembly [9].
• A nonsense mutation within the act88F actin gene disrupts myofibril formation in Drosophila indirect flight muscles [10].
• The cardiac actin protein, normally found only in myofibrils, is stably accumulated at a high level, about one-third that of the endogenous mouse beta-actin [11].

Chemical compound and disease context of Myofibrils

• In the present experiment, the triac-induced myofibrillar disarray but not the hypertrophy was prevented by propranolol, indicating that beta-adrenergic blockade or some other action of propranolol protects the developing myofibrils [12].
• Lesions of the myofibril in myopathic and normal tissue from seven striated muscles. Experimental myopathy of isometric activity produced by phencyclidine and restraint [13].
• In situ study of myofibrils, mitochondria and bound creatine kinases in experimental cardiomyopathies [14].
• Also examined are novel findings indicating that nebulin is actually a multifunctional filament system, perhaps playing roles in signal transduction, contractile regulation, and myofibril force generation; these ideas are especially intriguing given the growing number of mutations in this giant molecule that are associated with human myopathies [15].
• Necroses of myofibrils, characteristic of IPRO-induced lesions of adults, were, however, rather exceptional [16].

Biological context of Myofibrils

• Crt(-/-) EBs exhibited a severe decrease in expression and a lack of phosphorylation of ventricular myosin light chain 2 (MLC2v), resulting in an impaired organization of myofibrils [17].
• This suggests that additional proteins or posttranslational modifications of known costamere proteins are necessary to form a continuous linkage between the myofibrils and the extracellular matrix [18].
• To investigate the function of paramyosin in myofibril assembly and muscle contraction, we functionally disrupted the Drosophila melanogaster paramyosin gene by mobilizing a P element located in its promoter region [19].
• Recovery of postischemic function may be limited by energy synthesis by mitochondria, energy transfer via the creatine kinase reaction, or energy utilization at myofibrils [20].
• Changes did occur at the myofilament and cellular levels, with the myofibrils showing increased Ca(2+) sensitivity and significant deficits in relaxation in a transgene dose-dependent manner [21].

Anatomical context of Myofibrils

• Desmin and vimentin may thus be involved in maintaining the lateral registration of sarcomeres by transversely linking adjacent myofibrils at their Z discs [22].
• Two-dimensional gel electrophoresis has revealed that vimentin, the predominant subunit of intermediate filaments in cells of mesenchymal origin, is a component of isolated skeletal myofibrils [22].
• In striated muscle, it is believed that tight capping of the fast-growing (barbed) ends by CapZ and of the slow-growing (pointed) ends by tropomodulin (Tmod) stabilizes the uniform lengths of actin (thin) filaments in myofibrils [23].
• Sequential disassembly of myofibrils induced by myristate acetate in cultured myotubes [24].
• These results indicate that the alpha-actinin present in Z-bands of myofibrils is fully complexed with actin, but can bind exogenous alpha-actinin and, if actin is added subsequently, the exogenous alpha-actinin in the Z-band will bind the newly formed fluorescent actin filaments [25].

Associations of Myofibrils with chemical compounds

• The finding of an isoenzyme of creatine phosphokinase attached to the M-line region of the myofibril revealed the peripheral receptor for the mitochondrially generated phosphorylcreatine [26].
• Localization of creatine kinase isoenzymes in myofibrils. I. Chicken skeletal muscle [27].
• None of the tagged nebulin fragments behaved as dominant negatives; they neither blocked the assembly nor induced the disassembly of mature striated myofibrils [28].
• Treatment of crude myofibrils with 0.5% Triton X-100 results in the release of a 110,000-dalton component without affecting the myofibrillar structure [29].
• C protein was purified from extracts of detergent-washed myofibrils by sequential hydroxylapatite and DEAE-Sephacel chromatography [30].

Gene context of Myofibrils

• We used null mutations of Drosophila actin and myosin genes to investigate two aspects of myofibril assembly [31].
• Desmin is essential for the tensile strength and integrity of myofibrils but not for myogenic commitment, differentiation, and fusion of skeletal muscle [32].
• In contrast titin epitopes, which are present in mature myofibrils along the A band and at the A-I junction, are still randomly distributed [33].
• UNC-60B is normally localized in the diffuse cytoplasm and to the myofibrils in wild type but mislocalized to the actin aggregates in unc-78 mutants [34].
• Binding of an ankyrin-1 isoform to obscurin suggests a molecular link between the sarcoplasmic reticulum and myofibrils in striated muscles [35].

Analytical, diagnostic and therapeutic context of Myofibrils

• These observations strongly suggest that these Z bodies are the ultrastructural counterparts of the alpha-actinin dots seen by immunofluorescence optics and that they are formed nearly at the time of the formation of the first myofibrils [36].
• Immunoblotting demonstrated the presence of kettin isoforms in normal Drosophila IFM myofibrils and in myofibrils from an actin-null mutant [37].
• Immunoelectron microscopy of myofibrils identifies both titin-associated proteins as M band constituents [38].
• Confocal microscopy of rhodamine phalloidin-stained cells revealed that, within 24 hours of contractile arrest, actin filaments of myofibrils were no longer aligned with one another at their I bands and Z lines [39].
• Electron microscopy showed a significant increase in the distance between the sarcolemma and the nearest myofibrils, from less than 100 nm in controls to values as high as 550 nm in FSHD [40].

References