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PubMed2006

[Clinical consequences of muscle dysfunction in chronic obstructive pulmonary disease].

The function of respiratory muscles, and mainly inspiratory muscles, is impaired in COPD patients. Most of these impairments are essentially due to pulmonary hyperinflation that puts these muscles in a disadvantageous situation. The main consequence of this dysfunction is respiratory muscle fatigue that may cause shortness of breath, exertion intolerance, and hypoventilation with onset of hypercapnic respiratory failure. This function may be measured at the pulmonary function laboratory by means of unspecific (spirometry, pulmonary volumes) or specific tests (maxim respiratory pressures [MIP - M], transdiaphragmatic pressure, tension-time index of the diaphragm, electromyography, or endura tests). Therapy should aim at improving hyperinflation with bronchodilator therapy, improving muscular strength with rehabilitation, and in severe cases muscle rest with mechanical ventilation. Peripheral muscle dysfunction is a common complication in moderate-severe COPD, and it may be the result of chronic inactivity, hypoxemia, electrolytic impairments, under nutrition, steroids, oxidative stress, and systemic inflammation. Besides, it may contribute to patients' quality of life worsening, disability, and even an increase in morbimortality. It may tested by impedanciometry, muscle strength tests (dynamometry), imaging tests, and even muscle biopsy in research studies. Peripheral muscle dysfunction is potentially manageable with rehabilitation, nutritional supplementation, and anabolic drugs. However, therapeutic success is often incomplete, so that further studies with new therapeutic strategies are needed.

Humans↗

PubMedDate not supplied

[Ca2+]i in human heart failure: a review and discussion of current areas of controversy.

Multiple abnormalities have been reported in the setting of human heart failure. It is unclear whether detected changes reflect adaptive alterations in myocardium subjected to increased and sustained hemodynamic overload or are pathogenic to the disease process. As a result of the observation that the primary defect in heart failure is decreased pump function, investigators have concentrated their efforts on determining systolic [Ca2+]i as a logical corollary and a causative mechanism for contractile dysfunction. A simple cause and effect relationship has therefore been proposed with regard to contractile dysfunction and [Ca2+]i. Yet some investigators have found no difference in peak systolic [Ca2+]i between failing and non-failing human myocardium, whereas others have found peak [Ca2+]i to be significantly reduced in failing hearts. Resting calcium concentrations have been reported either to be elevated in failing human myocardium or not different from non-failing human myocardium. Investigators should now appreciate that the force-calcium relationship is not a simple relationship. One must take into account the prolonged time course and slowed mobilization of [Ca2+]i as opposed to simply peak [Ca2+]i. When put in perspective of mechanisms and determinants of the Ca(2+)-force relationship, we begin to realize that failing human myocardium has the "potential" to generate normal levels of force. Only when stressed by [Ca2+]i overload and/or frequency perturbation does myocardium from patients with end-stage heart disease demonstrate contractile failure. Although [Ca2+]i availability and mobilization are likely to play a role in the systolic as well as diastolic dysfunction reported in human heart failure, it is likely that other mechanisms are involved as well (e.g., myocardial energetics). Myocardial energetics is directly related to [Ca2+]i and mobilization in failing human myocardium, because metabolites, e.g., ADP, inhibit pumps, such as sarcoplasmic reticulum Ca2+ ATPase activity. We therefore conclude that there is a role for intracellular calcium mobilization and myocardial energetics for systolic and diastolic dysfunction seen in human heart failure.

Action Potentials↗

PubMed2001

Exercise-related female reproductive dysfunction.

Clinical or biochemical abnormalities of gonadal function, consisting of delayed puberty, luteal phase deficiency, oligo-amenorrhea or anovulation, occur in girls and women participating in strenuous sports. The evidence of a causal relationship between athletic activity and menstrual dysfunction has led to increased interest, also because the number of women who practice sports has increased rapidly. The pathogenesis of exercise-related female reproductive dysfunction (ERFRD) is not completely clarified. The heterogeneity of sports practice, the role of overtraining and other factors, as adequate calorie balance or the assumption of exogenous steroids, could play a primary role in the comprehension of the pathogenic mechanisms of reproductive dysfunction. The interest of physicians about ERFRD is also due to the consequences of reduced gonadal function on women's health. Apart from some short-term transient effects (i.e. on muscle, genito-urinary tract or behavior), hypoestrogenemia can induce long-term deleterious effects, as premature osteoporosis and lifelong impairment of skeletal structure. In view of the possible short-term (infertility) and long-term (osteoporosis) consequences of ERFRD, correct physical training and adequate diet approach are mandatory to prevent or to revert neuroendocrine abnormalities so frequently reported in girls and women participating in recreational or competitive athletic activities.

Energy Intake↗

PubMed2002

Treatment of heart failure with autologous skeletal myoblasts.

BACKGROUND: The management of patients with heart failure is a daily challenge for cardiologists and cardiac surgeons. Pharmacotherapy, atrio-biventricular resynchronization, myocardial revascularization, valve repair techniques, latissimus dorsi cardiomyopathy, acorn cardiac support device, heart transplantation and mechanical assist devices do not cover all the needs. The recent progress in cellular and molecular biology allows the development of new therapies for heart failure. TRANSPLANTATION OF AUTOLOGOUS CELLS: One of the most innovative consists in the transplantation of autologous ex-vivo expanded cells into the myocardium for heart muscle regeneration. This approach is called "cellular cardiomyoblasty".

Animals↗

PubMed1994

A mutant neurofilament subunit causes massive, selective motor neuron death: implications for the pathogenesis of human motor neuron disease.

A direct role of aberrant neurofilament accumulation in the etiology of human motor neuron diseases, including amyotrophic lateral sclerosis, is suggested by the presence of abnormal accumulations of neurofilaments as an early hallmark of the pathogenic process. Furthermore, forcing increased expression of neurofilament subunits in transgenic mouse models leads to motor neuron dysfunction, albeit without the widespread motor neuron death typical of human disease. We now show that accumulation of a modest level of a point mutant in the smallest neurofilament subunit (NF-L) causes massive, selective degeneration of spinal motor neurons accompanied by abnormal accumulations of neurofilaments and severe neurogenic atrophy of skeletal muscles. As in human disease, sensory neurons show only a modest level of degenerative changes. Thus, neurofilament mutations can cause selective motor neuron death, and neurofilamentous abnormalities may be a common toxic intermediate that significantly contributes to the motor neuron death in human disease.

Amino Acid Sequence↗

PubMed2004

Sildenafil: emerging cardiovascular indications.

The discovery in 1989 of sildenafil, a highly selective inhibitor of phosphodiesterase-5 (PDE-5), was the result of extensive research on chemical agents targeting PDE-5 that might potentially be useful in the treatment of coronary heart disease. Initial clinical studies on sildenafil in the early 1990s were not promising with respect to its antianginal potential. However, the incidental discovery of its antiimpotence effect led to its approval of for the treatment of erectile dysfunction. Thereafter, several reports of adverse cardiac events in patients on sildenafil raised concerns about its safety in cardiovascular disorders. Novel therapeutic indications are emerging for sildenafil with the recent discovery that PDE-5 is expressed in various other tissues such as the arterial vasculature, including pulmonary and coronary arteries, venous vasculature, skeletal muscles, platelets, and visceral and tracheobronchial muscles. In this review we briefly summarize the pharmacology of sildenafil and the current available evidence on its potential therapeutic applications in cardiovascular disorders.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2002

[Regional biochemical and hematologic changes in patients after revascularization of the lower extremities in ischemia of the extremities].

INTRODUCTION: Surgical treatment of PAOD is related to iatrogenic ischaemia caused by arterial clamping and ischaemia which is result of natural development of the disease. The pathway of skeletal muscle reperfusion injury is complex and one of the most important factors related to injury is endothelial damage. The expected reason of endothelial damage is increased production of oxygen free radicals by prematurely activated PMN (polymorphonuclear) leukocytes (direct injury). Non-specific tissue injury is related to releasing of PMN elastase. Endothelial dysfunction, hypercoagulable state and microcirculation stasis are responsible for indirect injury and no-reflow fenomena. STUDY DESIGN: Observational pilot study. METHODS: 10 patients underwent surgery because of PAOD (all suffering from critical limb ischaemia). During reperfusion period in defined intervals following parameters were measured (samples were taken from ipsilateral femoral vein): PMN elastase, lactate, total antioxidant status, malondialdehyd, minerals, acid-base balance, blood count, APTT, prothrombin time, fibrinogen and HTI (heparin tolerance index). RESULTS: Patients with PAOD are threatened by hypercoagulable state with its clinical and surgical consequences. Maximal grade of local acidosis is reached 2 hours from the beginning of reperfusion. Tissue damage is expressed by maximum activity of PMN elastase 18-24 hours during reperfusion and represents non-specific tissue damage. Low total antioxidant status reveals high sensibility to oxygen free radicals. MDA does not achieve the pathological range in observed series. CONCLUSION: Our results confirmed inevitable importance of prevention of hypercoagulability, oxygen free radical tissue damage and PMN elastase activation to avoid of non-specific tissue damage.

Antioxidants↗

PubMed2003

[Advance in calcium channel blockers relaxing corpus cavernosum smooth muscle].

Calcium channels exist extensively in the membrane of cardiac, skeletal, smooth muscle cell and neuron. Calcium channel blockers (CCB) were widely used for the treatment of cardiovascular diseases because they could relax vascular smooth muscle. Experimental researches on calcium channel blockers relaxing corpus cavernosum smooth muscle have been reported recently. Whether the blockers can be used for the clinical diagnosis and treatment of erectile dysfunction still need to be further investigated.

Animals↗

PubMed1983

Cardiac function in experimental uremia.

In acutely uremic animals, the contractile force of the heart is consistently increased; such an increase can be dissociated from changes of afterload or catecholaminergic drive. It is associated with diminished sarcolemmal Na,K-ATPase activity in the heart which, in turn, may be related to increased levels of endogenous digitalis-like substances (endigens) that have been postulated to represent a natriuretic factor. In patients with chronic uremia, myocardial contractility is usually normal, but occasionally there may be heart failure unrelated to pre-existing hypertension, coronary heart disease, anemia, fluid overload, or other recognizable factors. So far, the experimental basis for this clinical observation is uncertain. Possible causes for the clinical syndrome include an excess of parathyroid hormone or cardiodepressor substances. There is experimental evidence of impaired cardiac response to beta adrenergic agonists, e.g., decreased isoproterenol-dependent calcium uptake, diminished inotropic and chronotropic responses. In acutely uremic rats, cardiac cyclic AMP levels are high but can be reversed by beta blockers. Heart calcium content is variable and heart weight is constantly increased in acutely uremic rats, despite decreased skeletal muscle mass. The change in heart weight is not related to anemia, to an excess of parathyroid hormone, or to sympathetic activity; its cause remains unknown. Experimental studies to date have shown a variety of abnormalities, but do not provide a uniform concept of the mechanisms or an explanation for the cardiac dysfunction so often observed in patients with uremia.

Animals↗

PubMed2001

Cell therapy attenuates deleterious ventricular remodeling and improves cardiac performance after myocardial infarction.

BACKGROUND: Myocardial infarction (MI) promotes deleterious remodeling of the myocardium, resulting in ventricular dilation and pump dysfunction. We examined whether supplementing infarcted myocardium with skeletal myoblasts would (1) result in viable myoblast implants, (2) attenuate deleterious remodeling, and (3) enhance in vivo and ex vivo contractile performance. METHODS AND RESULTS: Experimental MI was induced by 1-hour coronary ligation followed by reperfusion in adult male Lewis rats. One week after MI, 10(6) myoblasts were injected directly into the infarct region. Three groups of animals were studied at 3 and 6 weeks after cell therapy: noninfarcted control (control), MI plus sham injection (MI), and MI plus cell injection (MI+cell). In vivo cardiac function was assessed by maximum exercise capacity testing and ex vivo function was determined by pressure-volume curves obtained from isolated, red cell-perfused, balloon-in-left ventricle (LV) hearts. MI and MI+cell hearts had indistinguishable infarct sizes of approximately 30% of the LV. At 3 and 6 weeks after cell therapy, 92% (13 of 14) of MI+cell hearts showed evidence of myoblast graft survival. MI+cell hearts exhibited attenuation of global ventricular dilation and reduced septum-to-free wall diameter compared with MI hearts not receiving cell therapy. Furthermore, cell therapy improved both post-MI in vivo exercise capacity and ex vivo LV systolic pressures. CONCLUSIONS: Implanted skeletal myoblasts form viable grafts in infarcted myocardium, resulting in enhanced post-MI exercise capacity and contractile function and attenuated ventricular dilation. These data illustrate that syngeneic myoblast implantation after MI improves both in vivo and ex vivo indexes of global ventricular dysfunction and deleterious remodeling and suggests that cellular implantation may be beneficial after MI.

Animals↗

PubMed1999

A nemaline myopathy mutation in alpha-tropomyosin causes defective regulation of striated muscle force production.

Nemaline myopathy (NM) is a rare autosomal dominant skeletal muscle myopathy characterized by severe muscle weakness and the subsequent appearance of nemaline rods within the muscle fibers. Recently, a missense mutation inTPM3, which encodes the slow skeletal alpha-tropomyosin (alphaTm), was linked to NM in a large kindred with an autosomal-dominant, childhood-onset form of the disease. We used adenoviral gene transfer to fully differentiated rat adult myocytes in vitro to determine the effects of NM mutant human alphaTm expression on striated muscle sarcomeric structure and contractile function. The mutant alphaTm was expressed and incorporated correctly into sarcomeres of adult muscle cells. The primary defect caused by expression of the mutant alphaTm was a decrease in the sensitivity of contraction to activating Ca(2+), which could help explain the hypotonia seen in NM. Interestingly, NM mutant alphaTm expression did not directly result in nemaline rod formation, which suggests that rod formation is secondary to contractile dysfunction and that load-dependent processes are likely involved in nemaline rod formation in vivo.

Adenoviridae↗

PubMed2006

Effects of congestive heart failure on Ca2+ handling in skeletal muscle during fatigue.

Skeletal muscle weakness and decreased exercise capacity are major symptoms reported by patients with congestive heart failure (CHF). Intriguingly, these skeletal muscle symptoms do not correlate with the decreased heart function. This suggests that CHF leads to maladaptive changes in skeletal muscles, and as reported most markedly in slow-twitch muscles. We used rats at 6 weeks after infarction to measure expression of key proteins involved in SR Ca(2+) release and uptake in slow-twitch soleus muscles. We also measured force and myoplasmic free [Ca(2+)] ([Ca(2+)](i)) in intact single fibers of soleus muscles. CHF rats showed clear signs of severe cardiac dysfunction with marked increases in heart weight and left ventricular end-diastolic pressure compared with sham operated rats (Sham). There were small, but significant, changes in the content of proteins involved in cellular Ca(2+) handling in CHF muscles: slight increases in SR Ca(2+) release channels (ie, the ryanodine receptors) and in SR Ca(2+)-ATPase. Tetanic force and [Ca(2+)](i) were not significantly different between CHF and Sham soleus fibers under resting conditions. However, during the stimulation period there was a decrease in tetanic force without changes in [Ca(2+)](i) in CHF fibers that was not observed in Sham fibers. The fatigue-induced changes recovered rapidly. We conclude that CHF soleus fibers fatigue more rapidly than Sham fibers because of a reversible fatigue-induced decrease in myofibrillar function.

Animals↗

PubMed2001

Biochemical and anatomical evidence for specialized voltage-dependent calcium channel gamma isoform expression in the epileptic and ataxic mouse, stargazer.

Inherited forms of ataxia and absence seizures in mice have been linked to defects in voltage-dependent calcium channel subunits. However, a correlation between the sites of neuronal dysfunction and the impact of the primary lesion upon calcium channel subunit expression or function has not been clearly established. For example, the mutation in stargazer mice has pleiotropic consequences including synaptic alterations in cerebellar granule cells, hippocampal CA3/mossy fibers, and cortical neurons in layer V that, presumably, lead to ataxia and seizures. Genetic analysis of stargazer mice determined that the defective gene encodes a protein expressed in brain (gamma2) with limited homology to the skeletal muscle L-type calcium channel gamma1 subunit. Although additional gamma isoforms have been subsequently identified primarily in neural tissue, little was known about the proteins they encode. Therefore, this study explored the distribution and biochemical properties of gamma2 and other gamma isoforms in wild-type and stargazer brain. We cloned human gamma2, gamma3, and gamma4 isoforms, produced specific anti-peptide antibodies to gamma isoforms and characterized both heterologously expressed and endogenous gamma. We identified regional specificity in the expression of gamma isoforms by western analysis and immunohistochemistry. We report for the first time that the mutation in the stargazer gene resulted in the loss of gamma2 protein. Furthermore, no compensatory changes in the expression of gamma3 or gamma4 protein were evident in stargazer brain. In contrast to other voltage-dependent calcium channel subunits, gamma immunostaining was striking in that it was primarily detected in regions highly enriched in excitatory glutamatergic synapses and faintly detected in cell bodies, suggesting a role for gamma in synaptic functions. Sites of known synaptic dysfunction in stargazer (the hippocampal CA3 region, dentate gyrus, and cerebellar molecular layer) were revealed as relying primarily upon gamma2, as total gamma isoform expression was dramatically decreased in these regions. Electron microscopy localized anti-gamma antibody immunostaining to dendritic structures of hippocampal mossy fiber synapses, with enrichment at postsynaptic densities. To assess the association of native gamma with voltage-dependent calcium channel or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits, gamma isoforms (gamma2, gamma3 and gamma4) were detergent solubilized from mouse forebrain. Antibodies against a highly conserved C-terminal epitope present in gamma2, gamma3 and gamma4 immunoprecipitated voltage-dependent calcium channel subunits (alpha1B), providing the first in vivo evidence that gamma and voltage-dependent calcium channels form stable complexes. Furthermore, both anti-gamma2 antibodies and anti-alpha1B antibodies independently immunoprecipitated the AMPA receptor subunit, GluR1, from mouse forebrain homogenates. In summary, loss of gamma2 immunoreactivity in stargazer is precisely localized so as to contribute to previously characterized synaptic defects. The data in this paper provide compelling evidence that gamma isoforms form complexes in vivo with voltage-dependent calcium channels as well as AMPA receptors, are selectively and differentially expressed in neuronal processes, and localize primarily to dendritic structures in the hippocampal mossy fiber region.

Animals↗

PubMed1998

Mitochondrial dysfunction of human muscle in chronic alcoholism detected by using 31P-magnetic resonance spectroscopy and near-infrared light absorption.

We previously examined the effect of alcohol on muscle energy metabolism in chronic alcoholics by using 31P-magnetic resonance spectroscopy. Measurements of intracellular pH and PCr index [PCr/(PCr + Pi)] during resting, hand grasping, and recovery in the left flexor digitorum superficialis muscle of alcoholics with neurological signs showed a marked decrease and delayed recovery of pH, but rapid recovery of PCr index indicating that the muscle produces lactate during and after exercise to maintain the ATP level. To clarify the reason for this preference for anaerobic metabolism, we conducted simultaneous measurements of the muscle blood supply during and after exercise by using the near-infrared light method and energy metabolism by using 31P-magnetic resonance spectroscopy. In alcoholics with neurological signs, we observed a significant increase of oxyhemoglobin after exercise with a slight increase of total hemoglobin. In healthy volunteers and chronic alcoholics without neurological signs, such an overshoot of oxyhemoglobin was not observed. We conclude that chronic alcoholics with neurological signs have an abnormality of aerobic metabolism owing to muscle mitochondrial dysfunction.

Acid-Base Equilibrium↗

PubMed2006

Exercise pressor reflex function is altered in spontaneously hypertensive rats.

In hypertension, exercise elicits excessive elevations in mean arterial pressure (MAP) and heart rate (HR) increasing the risk for adverse cardiac events and stroke during physical activity. The exercise pressor reflex (a neural drive originating in skeletal muscle), central command (a neural drive originating in cortical brain centres) and the tonically active arterial baroreflex contribute importantly to cardiovascular control during exercise. Each of these inputs potentially mediates the heightened cardiovascular response to physical activity in hypertension. However, given that exercise pressor reflex overactivity is known to elicit enhanced circulatory responses to exercise in disease states closely related to hypertension (e.g. heart failure), we tested the hypothesis that the exaggerated cardiovascular response to exercise in hypertension is mediated by an overactive exercise pressor reflex. To test this hypothesis, we used a rat model of exercise recently developed in our laboratory that selectively stimulates the exercise pressor reflex independent of central command and/or the arterial baroreflex. Activation of the exercise pressor reflex during electrically induced static muscle contraction in the absence of input from central command resulted in significantly larger increases in MAP and HR in male spontaneously hypertensive rats as compared to normotensive Wistar-Kyoto rats over a wide range of exercise intensities. Similar findings were obtained in animals in which input from both central command and the arterial baroreflex were eliminated. These findings suggest that the enhanced cardiovascular response to exercise in hypertension is mediated by an overactive exercise pressor reflex. Potentially, effective treatment of exercise pressor reflex dysfunction may reduce the cardiovascular risks associated with exercise in hypertension.

Animals↗

PubMed1997

Skeletal muscle oxygenation and oxygen uptake kinetics following constant work rate exercise in chronic congestive heart failure.

The aim of the present study was to determine the kinetics of recovery of muscle oxygenation (MO) from comparable levels of exercise in patients with chronic congestive heart failure (CHF) and in normal subjects, and to relate MO kinetics to the level of exercise intolerance. Ten patients with stable CHF secondary to ischemic cardiomyopathy (ejection fraction 34 +/- 6%) (mean age 47 +/- 10 years) and 8 healthy matched control subjects underwent an upright incremental cycle ergometer exercise test with gas exchange analysis and a 6-minute constant work rate protocol at 60% of peak oxygen consumption (VO2). Oxygenation of the vastus lateralis muscle was continuously monitored during exercise and recovery using near infrared spectroscopy. Recovery VO2 and MO mean response times for the constant work rate exercise test were longer in patients with CHF than in control subjects (p <0.05). Both VO2 and MO mean response times were inversely related to peak VO2 (r = -0.73 and -0.52, respectively; p <0.05 for both). Thus recovery of muscle and total body oxygenation from submaximal exercise is more delayed the greater the cardiac dysfunction, as assessed by peak VO2. This suggests that regeneration of phosphocreatine and/or resaturation of venous oxyhemoglobin take place more slowly the worse the cardiac function.

Adult↗

PubMedDate not supplied

The impact of vitamin C on diabetes induced alterations at murine neuromuscular junction.

Physiological functions of skeletal muscle are compromised in diabetes. This may involve free radical mechanisms and may be reversed by antioxidants. We have studied effects of vitamin C on twitch tension, resting membrane potential (RMP) and miniature endplate potentials (MEPPs) frequencies in dorsiflexor muscle of diabetic murine. Forty mice were divided randomly into 2 groups (n = 20 each). One group served as control and the other was injected once with streptozotocin (STZ) solution (60 mg/kg, i.p.) to induce diabetes. The animals were then divided further into two subgroups (n = 10 each). Vitamin C (200 mg/kg, i.p.) was administered daily to one control and one diabetic group for three weeks prior to recording day. Experiments were conducted four weeks following diabetes induction. Isometric twitch tension (evoked directly by muscle stimulation and indirectly by nerve stimulation) was measured in urethane anesthetized (2 mg/g, i.p.) mice via a transducer connected to computer system. Utilizing intracellular recording method, resting membrane potential RMP and MEPPs frequencies were also measured. Compared to control, diabetic mice showed reduced twitch tension (4.2 +/- 0.5 g control versus 2.6 +/- 0.2 g diabetic) and demonstrated delayed half time of decay. Diabetic flexor muscle also displayed significant reduction in MEPPs frequencies with no changes in RMP. Vitamin C reversed tension reduction in diabetic mice (from 2.6 +/- 0.2 g to 3.9 +/- 0.3 g), impacted delayed half time of decay and increased MEPPs frequencies. Vitamin C improves diabetes-induced nerve and muscle dysfunction possibly via a free radical scavenging mechanism.

Animals↗

PubMed2001

Association of syncoilin and desmin: linking intermediate filament proteins to the dystrophin-associated protein complex.

We recently identified a novel protein called syncoilin, a putative intermediate filament protein that interacts with alpha-dystrobrevin, a member of the dystrophin-associated protein complex. Syncoilin is found at the neuromuscular junction, sarcolemma, and Z-lines and is thought to be important for muscle fiber integrity. Based on the similar protein structure and cellular localization of syncoilin and desmin, we proposed that these proteins interact in vivo. The data presented confirm an interaction between syncoilin and desmin and demonstrate their co-localization in skeletal muscle. Intriguingly, whereas these proteins interact, COS-7 cell expression studies show that desmin and syncoilin do not assemble into heterofilaments. Furthermore, fractionation assay and immunofluorescence study of H2K myoblasts and myotubes suggest that, unlike typical intermediate filament proteins, syncoilin does not participate in filament formation with any protein. However, it is possible that syncoilin is involved in the anchoring of the desmin intermediate filament network at the sarcolemma and the neuromuscular junction. This interaction is likely to be important for maintaining muscle fiber integrity and may also link the dystrophin-associated protein complex to the cytoskeleton. The dysfunction or absence of syncoilin may result in the disruption of the intermediate filament network leading to muscle necrosis. Syncoilin is therefore an ideal candidate gene for muscular dystrophies and desmin-related myopathies.

Animals↗