Modification of the functional capacity of sarcoplasmic reticulum membranes in patients suffering from chronic fatigue syndrome

Laboratorio Interuniversitario di Miologia, Università 'G. d'Annunzio', Nuovo Polo Didattico, 66013 Chieti Scalo, Italy.
Neuromuscular Disorders (Impact Factor: 2.64). 09/2003; 13(6):479-84. DOI: 10.1016/S0960-8966(03)00042-7
Source: PubMed


In chronic fatigue syndrome, several reported alterations may be related to specific oxidative modifications in muscle. Since sarcoplasmic reticulum membranes are the basic structures involved in excitation-contraction coupling and the thiol groups of Ca(2+) channels of SR terminal cisternae are specific targets for reactive oxygen species, it is possible that excitation-contraction coupling is involved in this pathology. We investigated the possibility that abnormalities in this compartment are involved in the pathogenesis of chronic fatigue syndrome and consequently responsible for characteristic fatigue. The data presented here support this hypothesis and indicate that the sarcolemmal conduction system and some aspects of Ca(2+) transport are negatively influenced in chronic fatigue syndrome. In fact, both deregulation of pump activities (Na(+)/K(+) and Ca(2+)-ATPase) and alteration in the opening status of ryanodine channels may result from increased membrane fluidity involving sarcoplasmic reticulum membranes.

Download full-text


Available from: Stefania Fulle, Oct 08, 2015
31 Reads
  • Source
    • "This binding assay was performed with membranes purified from the wild-type and MLC/mIGF-1 mature myotubes sonicated in sodium phosphate buffer (20 mM NaPO4, pH 7.0) supplemented with protease inhibitors according to a procedure described by Fulle et al. [22]. The dihydropyridine receptor (DHPR) concentrations were determined using the radioligand [3H]-PN200-110. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Muscle regeneration involves the activation of satellite cells, is regulated at the genetic and epigenetic levels, and is strongly influenced by gene activation and environmental conditions. The aim of this study was to determine whether the overexpression of mIGF-1 can modify functional features of satellite cells during the differentiation process, particularly in relation to modifications of intracellular Ca2+ handling. Satellite cells were isolated from wild-type and MLC/mIGF-1 transgenic mice. The cells were differentiated in vitro, and morphological analyses, intracellular Ca2+ measurements, and ionic current recordings were performed. mIGF-1 overexpression accelerates satellite cell differentiation and promotes myotube hypertrophy. In addition, mIGF-1 overexpression-induced potentiation of myogenesis triggers both quantitative and qualitative changes to the control of intracellular Ca2+ handling. In particular, the differentiated MLC/mIGF-1 transgenic myotubes have reduced velocity and amplitude of intracellular Ca2+ increases after stimulation with caffeine, KCl and acetylcholine. This appears to be due, at least in part, to changes in the physico-chemical state of the sarcolemma (increased membrane lipid oxidation, increased output currents) and to increased expression of dihydropyridine voltage-operated Ca2+ channels. Interestingly, extracellular ATP and GTP evoke intracellular Ca2+ mobilization to greater extents in the MLC/mIGF-1 transgenic satellite cells, compared to the wild-type cells. These data suggest that these MLC/mIGF-1 transgenic satellite cells are more sensitive to trophic stimuli, which can potentiate the effects of mIGF-1 on the myogenic programme.
    PLoS ONE 09/2014; 9(9):e107753. DOI:10.1371/journal.pone.0107753 · 3.23 Impact Factor
  • Source
    • "Increased activity of Na + /K + -ATPase has been reported in several other pathological conditions such as in experimentally induced epilepsy (Fernandes et al., 1996; Reime et al., 2007), and in Crush syndrome (Desai and Desai, 2007). In chronic fatigue syndrome, the activities of both Na + / K + -ATPase and Ca 2+ /Mg 2+ -ATPase are increased in sarcoplasmic reticulum membranes (Fulle et al., 2003). In addition, Takser et al. (2003) reported a correlation of ATPase activities with early psychomotor development in humans. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase are enzymes known to maintain intracellular gradients of ions that are essential for signal transduction. The aim of this study was to compare the activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase in postmortem brain samples from the cerebellum and frontal, temporal, parietal, and occipital cortices from autistic and age-matched control subjects. The frozen postmortem tissues from different brain regions of autistic and control subjects were homogenized. The activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase were assessed in the brain homogenates by measuring inorganic phosphorus released by the action of Na(+)/K(+)- and Ca(2+)/Mg(2+)-dependent hydrolysis of ATP. In the cerebellum, the activities of both Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase were significantly increased in the autistic samples compared with their age-matched controls. The activity of Na(+)/K(+)-ATPase but not Ca(2+)/Mg(2+)-ATPase was also significantly increased in the frontal cortex of the autistic samples as compared to the age-matched controls. In contrast, in other regions, i.e., the temporal, parietal and occipital cortices, the activities of these enzymes were similar in autism and control groups. The results of this study suggest brain-region specific increases in the activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase in autism. Increased activity of these enzymes in the frontal cortex and cerebellum may be due to compensatory responses to increased intracellular calcium concentration in autism. We suggest that altered activities of these enzymes may contribute to abnormal neuronal circuit functioning in autism.
    Life sciences 10/2009; 85(23-26):788-93. DOI:10.1016/j.lfs.2009.10.008 · 2.70 Impact Factor
  • Source
    • "In vitro studies performed with CFS muscle sarcoplasmic membranes indicate a diminished capacity of RyR-channels derived from pathological muscles to be maintained in the open status. This finding was confirmed in experiments in which caffeine (an alkaloid that stimulates the opening of SR Ca 2+ channels) was unable to activate full load Ca 2+ release from RyR (Fulle et al. 2003). Compared to healthy sedentary people, CFS patients display significantly decreased exercise capacity, similar to that recorded in an aged population (CFS = old muscle in young body). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic fatigue syndrome (CFS) is a relatively common disorder defined as a status of severe persistent disabling fatigue and subjective unwellness. While the biological basis of the pathology of this disease has recently been confirmed, its pathophysiology remains to be elucidated. Moreover, since the causes of CFS have not been identified, treatment programs are directed at symptom relief, with the ultimate goal of the patient regaining some level of pre-existing function and well-being. Several studies have examined whether CFS is associated with: (i) a range of infectious agents and or immune disturbance; (ii) specific changes of activity in the central or peripheral nervous systems; and (iii) elevated stress periods, which may be associated with the pathology via genetic mechanisms. The role of oxidative stress in CFS is an emerging focus of research due to evidence of its association with some pathological features of this syndrome. New data collectively support the presence of specific critical points in the muscle that are affected by free radicals and in view of these considerations, the possible role of skeletal muscle oxidative imbalance in the genesis of CFS is discussed.
    Journal of Muscle Research and Cell Motility 02/2007; 28(6):355-62. DOI:10.1007/s10974-008-9128-y · 2.09 Impact Factor
Show more