Gotowa bibliografia na temat „Muscle Cytoarchitecture”

The aim of this study was to assess the changes which occurred in the rat in target muscles after the injury and repair of a specific peripheral nerve, using several clinically-appropriate surgical techniques. There were alterations in the size, shape, morphology and cytochemical architecture of the fibres of the target muscles. These changes were marked when transection and repair of the nerve was compared with the less-severe crush injury. The method of repair did not correlate significantly with the occurrence of changes in muscle cytoarchitecture. The results suggest that the extent of cell loss and the changes in muscle fibre architecture were influenced by the type of injury, rather than by the method of repair.

Part of the muscle creatine kinase (MM-CK) in skeletal muscle of chicken is localized in the M-band of myofibrils, while chicken heart cells containing myofibrils and BB-CK, but not expressing MM-CK, do not show this association. The specificity of the MM-CK interaction was tested using cultured chicken heart cells as "living test tubes" by microinjection of in vitro generated MM-CK and hybrid M-CK/B-CK mRNA with SP6 RNA polymerase. The resulting translation products were detected in injected cells with isoprotein-specific antibodies. M-CK molecules and translation products of chimeric cDNA molecules containing the head half of the B-CK and the tail half of the M-CK coding regions were localized in the M-band of the myofibrils. The tail, but not the head portion of M-CK is essential for the association of M-CK with the M-band of myofibrils. We conclude that gross biochemical properties do not always coincide with a molecule's specific functions like the participation in cell cytoarchitecture which may depend on molecular targeting even within the same cellular compartment.

✓ The three-dimensional cytoarchitecture of the smooth muscles and pericytes of rat cerebral blood vessels was studied by scanning electron microscopy after removing extracellular connective tissue matrices with the KOH-collagenase digestion method. The tunica media of major intracranial arteries such as the internal carotid, vertebral, basilar, and other cerebral arteries measuring more than 100 µm in outer diameter consisted of spindle-shaped smooth-muscle cells arranged circularly to the long axis of the vessel. Muscle cells at the branching points, however, showed a variety of shapes, sizes, and arrangements. As the vessel size decreased, smooth-muscle cells showed bi- or trifurcations at the cell poles. In the precapillary arterioles, smooth-muscle cells which had helically surrounded the endothelial tubes had bulging cell bodies with various cytoplasmic processes extending from the cell poles. Distinct specializations presumed to be sphincters were not found on the arteries or arterioles. Pericytes of the capillary had become extended along the vessel axis, having fusiform cell bodies with longitudinally oriented long cytoplasmic processes. Cells located periendothelially in the venules and veins were stellate in shape with many cytoplasmic processes which were interwoven to form complicated cellular networks around the endothelial tube.

Syncoilin is a striated muscle-specific intermediate filament-like protein, which is part of the dystrophin-associated protein complex (DPC) at the sarcolemma and provides a link between the extracellular matrix and the cytoskeleton through its interaction with α-dystrobrevin and desmin. Its upregulation in various neuromuscular diseases suggests that syncoilin may play a role in human myopathies. To study the functional role of syncoilin in cardiac and skeletal muscle in vivo, we generated syncoilin-deficient ( syncoilin−/−) mice. Our detailed analysis of these mice up to 2 yr of age revealed that syncoilin is entirely dispensable for cardiac and skeletal muscle development and maintenance of cellular structure but is required for efficient lateral force transmission during skeletal muscle contraction. Notably, syncoilin−/− skeletal muscle generates less maximal isometric stress than wild-type (WT) muscle but is as equally susceptible to eccentric contraction-induced injury as WT muscle. This suggests that syncoilin may play a supportive role for desmin in the efficient coupling of mechanical stress between the myofibril and fiber exterior. It is possible that the reduction in isometric stress production may predispose the syncoilin skeletal muscle to a dystrophic condition.

Myofibrillogenesis is a complex process involving assembly of many structural proteins in an orchestrated spatio-temporal manner to form a highly ordered contractile sarcomeric unit. Mutations in the proteins involved in muscle contraction and function lead to myopathic conditions in human. Hence, understanding the etiology of these diseases and genes involved may help in accurate diagnosis, prognosis and exploration of possible therapeutics. Molecular players and signaling pathways of myogenesis are highly conserved across phyla, enabling us to exploit indirect flight muscles (IFM) of Drosophila melanogaster as a model to study muscle development and function. IFM is the only fibrillar muscle which has considerable functional similarity to vertebrate cardiac muscles. It also enables the analyses of all stages of muscle development from its earliest stages of fusion of the imaginal myoblasts to fully differentiated muscle with its assembled contractile apparatus. Perturbance of developmental process in IFM leads to flightless flies with dysfunctional muscle. High throughput mutant screens, designed to isolate flightless flies have led to the identification of large number of genetic loci which are involved in muscle patterning and myofibrillogenesis, thus giving useful insights into the structural and functional aspects of fibre formation. One such classical mutant, flightless H (fliH), isolated during mutagenesis screen leads to IFM degeneration after fibres are formed normally. This interesting phenomenon is designated as muscle hypercontraction and is comparable to hypertrophic cardiomyopathies in humans. The muscle hypercontraction phenotype in this mutant was found to be temperature dependent and development of the process initiated at later stages of pupation. Cellular events associated with the IFM hypercontraction were followed up through development using this mutant. Further, interaction of fliH allele with other genetic backgrounds gave valuable insights on mechanisms of causation of muscle hypercontraction. Genetics played a pivotal role in identifying the mutant locus. The mutation was genetically mapped to the regulatory region of the wupA gene which was confirmed by sequencing data. The wupA gene codes for Troponin I (TnI), an inhibitory component of the troponin-tropomyosin complex of thin filaments. The mutation leads to reduced level of TnI transcript and hence reduced amount of protein, as a consequence, troponin complex formation is impeded leading to uninhibited acto-myosin interactions, thus causing muscle fibre breakdown. Our study reveals that fliH is a unique allele which confers temperature sensitive muscle phenotype. This is the first mutation found in the regulatory region of any structural gene which is temperature dependant and leads to muscle hypercontraction. This study also emphasizes that stoichiometry of structural proteins is important for proper functioning of muscle. Apart from mutations in sarcomeric genes, perturbations in calcium signaling also affect muscle functioning and lead to development of cardiac hypertrophy and failure. Hence, the role of calcineurin β-subunit (canB2), a calcium dependant protein phosphatase, in muscle was analyzed. Studies involving overexpression of canB2 in IFM showed that it leads to muscle hypercontraction. In addition, characterization of one of the new allele generated for the present study confirmed presence of muscle tearing and sarcomeric structure abnormality. canB2 alleles genetically interact with other hypercontracting alleles and enhance the hypercontraction phenotype. Overall, present study will help us to understand how genetic predisposition can enhance or suppress muscle hypercontraction. In a reverse genetics approach, role of muscle LIM protein, Beadex (Bx) in IFM was analyzed, as point mutations and loss of function alleles of LIM genes are associated with cardiomyopathies in humans. Immuno-histochemistry showed that Bx is expressed in myoblasts associated with wing imaginal disc which gives rise to IFM. Expression is also seen in developing IFM and in the neurons innervating the IFM. However, unlike the other known LIM proteins in Drosophila, Bx was not adhered to muscle fibre and showed predominant cytosolic localization. Targeted knockout and over-expression in muscles showed fibre rupturing and Z-disc deformities. Our results suggest that Bx may be involved in mechano-sensory stress signaling pathway like the other LIM proteins in humans and proper maintenance of the sarcomeric structure. Thus, present study elucidates the role of three loci namely: wupA, canB2 and Bx in proper muscle development and function. All the three loci code for proteins having orthologues in higher vertebrates and have been implicated in the pathogenesis of cardiomyopathies and/or skeletal myopathies in humans. Overall, such studies involving analyses of genes implicated in muscle development and function will help in exploring disease pathways which may help in derivation of new therapeutic strategies.