1,721,007 research outputs found
Selective maintenance of neurotrophically regulated proteins in denervated rat diaphragm
No full textExp Neurol. 1979 Mar;63(3):468-75.
Selective maintenance of neurotrophically regulated proteins in denervated rat diaphragm.
Carraro U, Catani C, Biral D.
PMID:
155010
[PubMed - indexed for MEDLINE
Loss of Dystrophin and Some Dystrophin-Associated Proteins with Concomitant Signs of Apoptosis in Rat Leg Muscle Overworked in Extension
No full textActa Neuropathol. 2000 Dec;100(6):618-26.
Loss of dystrophin and some dystrophin-associated proteins with concomitant signs of apoptosis in rat leg muscle overworked in extension.
Biral D, Jakubiec-Puka A, Ciechomska I, Sandri M, Rossini K, Carraro U, Betto R.
Source
C.N.R. Unit for Muscle Biology and Physiopathology, Padova, Italy.
Abstract
This study investigated the basis for the high severity of damage to skeletal muscle due to eccentric exercise, i.e., to muscles generating force while lengthened. Fast and slow rat leg muscles maintained in an extended position were examined after 2-24 h of continuous stimulation. The treatment caused the injury to some regions of both muscles. Within the better preserved parts of the muscles, i.e., those without signs of necrotic processes, dystrophin, spectrin, and some of the dystrophin-associated proteins (beta-dystroglycan, alpha-sarcoglycan, and gamma-sarcoglycan) disappeared from sarcolemma of many fibers. The reduction or loss of dystrophin from the sarcolemma was more evident than that of other proteins examined, with sarcoglycans apparently being the most preserved. Several muscle fibers devoid of dystrophin contained apoptotic nuclei. Simultaneously, Bax, Bcl-2 and caspase-3 proteins appeared in many fibers. Our results indicate that a normal muscle overworking in an extended position undergoes the loss of several membrane skeletal proteins because of the excessive stress to the membrane cytoskeleton, which can lead to fiber death by either apoptosis or necrosis. This experimental model may represent a good model for mimicking the pathogenetic events in several muscular dystrophies.
PMID:
11078213
[PubMed - indexed for MEDLINE
Atrophy-resistant fibers in permanent peripheral denervation of human skeletal muscle
No full textNeurol Res. 2008 Mar;30(2):137-44.
Atrophy-resistant fibers in permanent peripheral denervation of human skeletal muscle.
Biral D, Kern H, Adami N, Boncompagni S, Protasi F, Carraro U.
Source
Italian C.N.R. Institute of Neuroscience, and Laboratory of Translational Myology, Interdepartmental Research Center of Myology, c/o Department of Biomedical Sciences, University of Padova, I-35121 Padova, Italy.
Abstract
OBJECTIVE:
Human muscle fibers usually undergo severe atrophy/degeneration as a result of long-term peripheral denervation. However, some biopsies from paraplegic patients suffering complete conus cauda syndrome display the presence of a small percentage of muscle fibers with a very large diameter (big fibers). The objective of the present study is to determine if these big fibers are the result of residual innervation/reinnervation, or if instead they are fibers resistant to atrophy.
METHODS:
Human muscle biopsies were harvested from the vastus lateralis of spinal cord injury (SCI) patients affected by complete lower motor neuron lesion (LML). The specimens were either processed for light microscopy or embedded for electron microscopy (EM).
RESULTS:
Our results indicate that the big fibers are neither the results of residual innervation or sparse reinnervation. In spite of the fact that the extrasynaptic NCAM immunostaining disappear a few months after SCI, the big fibers are characterized by positive molecular markers of denervation, that is, the differential labeling of their dystrophin molecule by anti-C and anti-N terminals antibodies. Furthermore, the EM analysis shows that these cells present the peculiar ultrastructural disarrangements of the contractile apparatus and of the internal membrane systems characteristic of 'peripheral denervation'. No fibers presenting large areas of cross-striation were found. The EM analysis provides the final evidence that these big fibers are muscle fibers which are indeed denervated, very different from normal and/or disused (e.g. upper motor neuron lesion) muscle fibers.
DISCUSSION:
Although these large muscle fibers are surprisingly more frequent in human muscle biopsies after 3 years from SCI than earlier, it remains to be determined whether their presence in some biopsies but not in others is caused by sampling, or is related to other factors such as to subjects' background genetics, or the extent of passive stretching induced by different rehabilitation strategies.
PMID:
18397604
[PubMed - indexed for MEDLINE
Functional roles of dystrophin and of associated proteins. New insights for the sarcoglycans
No full textThe discovery of the dystrophin gene, whose mutations lead to Duchenne's and Becker's muscular dystrophy (DMD and BMD), represents the first important landmark by which, in the last ten years, molecular biology and genetic studies have revealed many of the molecular defects of the major muscular dystrophies. Very rapidly, several studies revealed the presence at skeletal and cardiac muscle sarcolemma of a group of proteins associated to dystrophin. This includes a set of five transmembrane glycoproteins, the sarcoglycans, whose physiological role, however, is still poorly understood. Dystrophin and the associated proteins are believed to play an important role in membrane stability and maintenance during muscle contraction and relaxation. However, the absence of sarcoglycans from sarcolemma does not appear to affect membrane integrity suggesting that these components of the dystrophin complex are recipients of other important functions. This review deals with recent advances in the knowledge of sarcoglycan function and organization that may give important insights into the pathogenetic mechanisms of muscular dystrophies
Subclinical myopathy in patients affected with newly diagnosed colorectal cancer at clinical onset of disease: evidence from skeletal muscle biopsies.
No full textNeurol Res. 2010 Feb;32(1):20-5. Epub 2009 Nov 26.
Subclinical myopathy in patients affected with newly diagnosed colorectal cancer at clinical onset of disease: evidence from skeletal muscle biopsies.
Zampieri S, Doria A, Adami N, Biral D, Vecchiato M, Savastano S, Corbianco S, Carraro U, Merigliano S.
Source
Laboratory of Translational Myology, Interdepartmental Research Center of Myology, c/o, Department of Biomedical Science, University of Padova, Padova, Italy. [email protected]
Abstract
OBJECTIVE:
To evaluate skeletal muscle biopsy from asymptomatic patients affected with newly diagnosed colorectal cancer and to identify pathological features which may be indicative of tumor-associated muscle disorders, potentially leading to cachexia.
METHODS:
Patients affected with newly diagnosed colorectal cancer at clinical onset of disease underwent biopsy of the rectus abdominis muscle during elective laparoscopic tumor resection, before chemotherapeutic treatment. Morphometric analyses, ATPase histochemistry and immunohistochemical studies using antibodies directed to N-CAM and to MHC-emb, two sound makers of muscle denervation and injury-induced muscle regeneration, were performed on intraoperative muscle biopsies from ten patients. Muscle biopsies from rectus abdominis of seven subjects affected with non-neoplastic condition, which underwent laparoscopic surgery, were used as controls.
RESULTS:
In patients' biopsies, we observed a surprisingly high percentage of myofibers with internalized or central nuclei compared to controls (9.15 +/- 8.9 versus 0.6 +/- 0.9, p<0.0003). In addition, in the 30% of patients, small myofibers expressing the MHC-emb have been identified (0.4 +/- 0.5 positive fibers/mm(2)), while in 50% of patients, larger fibers positive for N-CAM have also been detected (0.7 +/- 1.1 positive fibers/mm(2)), suggesting that investigated muscle biopsies exhibit other evidence of muscle fiber injury/regeneration and/or denervation. Among the 10,000 analysed myofibers in control biopsies, no MHC-emb and N-CAM-positive muscle fibers have been detected. Thus, patients affected with newly diagnosed colorectal cancer at clinical onset of disease display early signs of a subclinical myopathy.
DISCUSSION:
Factors and mechanisms of this cancer-associated myopathy are yet unknown. The facts that the great majority of the abnormally nucleated myofibers are of the fast type and that regenerating myofibers are present, suggest a myogenic response to the colorectal cancer and not to the laparoscopic modalities of the biopsy harvesting. Follow-up of the patients will elucidate the clinical relevance of our observation, and further studies investigating the molecular mechanism underlying this early cancer-associated myopathy will hopefully provide some pathogenetic clues leading to the identification of potential specific targets for therapeutic intervention to prevent tumor cachexia.
PMID:
19941733
[PubMed - indexed for MEDLINE
Myosin subunit composition in human developing muscle.
No full textPrevious pyrophosphate-gel studies have reported the existence of embryonic neonatal myosin isoenzymes in human developing muscle. The present investigation was undertaken to characterize their subunit composition more precisely. Two immature muscle myosins are contrasted with adult myosin: neonatal myosin and foetal myosin. The neonatal form of myosin is weakly cross-reactive with rabbit slow myosin and contains only fast-type light chains (LC), LC1F and LC2F. The associated heavy chains consist of a single electrophoretic component that reacts exclusively with antibodies against human foetal myosin and has a mobility and peptide pattern distinct from that of adult fast and slow heavy chains. Foetal myosin is distinguished by the presence of low amounts of a heavy chain immunologically cross-reactive with the adult slow form and of two additional light-chain components: a LC2S light chain and a foetal-specific light chain (LCemb.). The foetal-specific light chain, as shown by one-dimensional-peptide-map analysis, is structurally unrelated to both LC1S and LC1F light chains of human adult myosin. We conclude from these results that the ontogenesis of human muscle myosin shares certain common features with that observed in other species, except for the persistence until birth of a foetal form of heavy chain (HCemb.)
Ontogenesis of chick iris intrinsic muscles: evidence for a smooth-to-striated muscle transition.
No full textThe iris sphincter muscle consists of striated muscle fibers in the adult chicken. The ontogenetic development of this muscle has been studied by immunocytochemistry, from Embryonic Day 7 to the time of hatching. The time course of expression of specific markers of either smooth or striated muscle, i.e., smooth and skeletal muscle myosin heavy chains along with the inositol 1,4,5-trisphosphate (IP3) receptor, the intracellular Ca2+ release channel gated by the second messenger IP3, was investigated. We observed the parallel and transient expression, from about Embryonic Day 8 until hatching, of smooth muscle myosin heavy chain and IP3 receptor in early differentiating cells at the pupillary margin, as well as in migrating cells at subsequent stages; the sequential expression of sarcomeric myosin heavy chain around the end of the second embryonic week; and its spreading throughout the iris sphincter by the time of hatching. The present findings are consistent with a smooth muscle differentiation stage as an intermediate stage in the ontogenic development of the iris sphincter muscle of the chicken
Effects of fatigue on sarcoplasmic reticulum and myofibrillar properties of rat slow-and fast-twitch muscle fibers
No full textForce decline during fatigue in skeletal muscle is attributed mainly to progressive alterations of the intracellular milieu. Metabolite changes and the decline in free myoplasmic calcium influence the activation and contractile processes. This study was aimed at evaluating whether fatigue also causes persistent modifications of key myofibrillar and sarcoplasmic reticulum (SR) proteins that contribute to tension reduction. The presence of such modifications was investigated in chemically skinned fibers, a procedure that replaces the fatigued cytoplasm from the muscle fiber with a normal medium. Myofibrillar Ca(2+) sensitivity was reduced in slow-twitch muscle (for example, the pCa value corresponding to 50% of maximum tension was 6.23 +/- 0.03 vs. 5.99 + 0.05, P < 0.01, in rested and fatigued fibers) and not modified in fast-twitch muscle. Phosphorylation of the regulatory myosin light chain isoform increased in fast-twitch muscle. The rate of SR Ca(2+) uptake was increased in slow-twitch muscle fibers (14.2 +/- 1.0 vs. 19.6 +/- 2. 5 nmol. min(-1). mg fiber protein(-1), P < 0.05) and not altered in fast-twitch fibers. No persistent modifications of SR Ca(2+) release properties were found. These results indicate that persistent modifications of myofibrillar and SR properties contribute to fatigue-induced muscle force decline only in slow fibers. These alterations may be either enhanced or counteracted, in vivo, by the metabolic changes that normally occur during fatigue development
Role of dystrophin and dystrophin-associated proteins in the pathogenesis of muscular dystrophies
No full textIdentification and localization of the myotonic dystrophy gene product in skeletal and cardiac muscles
No full textWe have raised a polyclonal antibody against a synthetic peptide chosen within the deduced sequence of the myotonic dystrophy gene product. This antibody binds to a protein whose molecular weight is in the range of 50-54 kDa in Western blotting of rat, rabbit and human muscles. Biochemical studies seem to indicate that this protein is a peripheral component of sarcoplasmic reticulum as well as of plasma membrane
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