The Arianna thread: the matching of S-100 family with the RyR's muscle receptor.

The functional state of RyR depends on the intracellular calcium concentration and on the oxidation state of its protein components in some particular sites and of some sentinel amino acids. In addition to the regulation of the RyR channel by exogenous substances (caffeine, ryanodine), ions environmental situations (oxidative state), other components, such as some endogenous proteins present in the sarcoplasm and/or in muscle membranes that are able to determine changes in Ca channel activity. Among these, calmodulin and S-100A could determine modifications in the status of RyR channel in the skeletal muscle.

Association of A Novel Splice Site Mutation in P/Q-Type Calcium Channels with Childhood Epilepsy and Late-Onset Slowly Progressive Non-Episodic Cerebellar Ataxia.

Episodic ataxia type 2 (EA2) is characterized by paroxysmal attacks of ataxia with typical onset in childhood or early adolescence. The disease is associated with mutations in the voltage-gated calcium channel alpha 1A subunit (Cav2.1) that is encoded by the gene.

Small heat shock proteins in the amphibian Pelophylax bergeri: Cloning and characterization of Hsp27 and Hsp30 cDNAs and their expression analysis in ex vivo skin exposed to abiotic stresses.

Small Heat Shock Proteins (sHSP) are molecular chaperones that play an essential role in maintaining protein homeostasis and promoting cell survival. In this work, for the first time, multiple cDNAs encoding for small Hsp27 and Hsp30, designed, respectively, as PbHsp27-(1-2) and PbHsp30-(1-5), were cloned and characterized in the amphibian Pelophylax bergeri, which is a suitable model for studying biological responses to environmental perturbations. Domain architecture analysis showed that PbHsp27 and PbHsp30 cDNAs displayed the typical signature motifs of the sHSP family such as the conserved α-crystallin domain flanked by variable N-terminal and C-terminal regions.

Dexamethasone in Glioblastoma Multiforme Therapy: Mechanisms and Controversies.

Glioblastoma multiforme (GBM) is the most common and malignant of the glial tumors. The world-wide estimates of new cases and deaths annually are remarkable, making GBM a crucial public health issue. Despite the combination of radical surgery, radio and chemotherapy prognosis is extremely poor (median survival is approximately 1 year).

Hypoxia Modulates the Swelling-Activated Cl Current in Human Glioblastoma Cells: Role in Volume Regulation and Cell Survival.

The malignancy of glioblastoma multiforme (GBM), the most common human brain tumor, correlates with the presence of hypoxic areas, but the underlying mechanisms are unclear. GBM cells express abundant Cl channels whose activity supports cell volume and membrane potential changes, ultimately leading to cell proliferation, migration, and escaping death. In non-tumor tissues Cl channels are modulated by hypoxia, which prompted us to verify whether hypoxia would also modulate Cl channels in GBM cells.

Short-term cadmium exposure induces stress responses in frog (Pelophylax bergeri) skin organ culture.

There have been a few studies on the negative effects of pollutants on amphibian skin, the first structural barrier that interacts with the environment and its potential contaminants. In this study an ex vivo skin organ culture from the amphibian Pelophylax bergeri was used to evaluate cell stress responses induced by short-term exposure to cadmium (Cd), a toxic heavy metal known to be an environmental hazard to both humans and wildlife. Histopathological studies were carried out on skin explants using light microscopy and changes in the expression of stress proteins, such as Metallothionein (MT) and Heat shock proteins (HSPs), were investigated by Real-time RT-PCR.

Reconciling the discrepancies on the involvement of large-conductance Ca(2+)-activated K channels in glioblastoma cell migration.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor, and is notable for spreading so effectively through the brain parenchyma to make complete surgical resection virtually impossible, and prospect of life dismal. Several ion channels have been involved in GBM migration and invasion, due to their critical role in supporting volume changes and Ca(2+) influx occuring during the process. The large-conductance, Ca(2+)-activated K (BK) channels, markedly overexpressed in biopsies of patients with GBMs and in GBM cell lines, have attracted much interest and have been suggested to play a central role in cell migration and invasion as candidate channels for providing the ion efflux and consequent water extrusion that allow cell shrinkage during migration.

The role of ion channels in the hypoxia-induced aggressiveness of glioblastoma.

The malignancy of glioblastoma multiform (GBM), the most common and aggressive form of human brain tumors, strongly correlates with the presence of hypoxic areas, but the mechanisms controlling the hypoxia-induced aggressiveness are still unclear. GBM cells express a number of ion channels whose activity supports cell volume changes and increases in the cytosolic Ca(2+) concentration, ultimately leading to cell proliferation, migration or death. In several cell types it has previously been shown that low oxygen levels regulate the expression and activity of these channels, and more recent data indicate that this also occurs in GBM cells.

New insights into the relationship between mIGF-1-induced hypertrophy and Ca2+ handling in differentiated satellite cells.

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.

Oxidative balance in lymphocytes from patients with nonalcoholic steatohepatitis.

Oxidative stress is linked to several human diseases, including nonalcoholic steatohepatitis (NASH). In this study, lymphocytes were used as a model to study this disease. These cells offer several advantages for cellular and molecular studies such as easy accessibility, and they are easily accessible and constitute a "time-persistent" system capable of reflecting the condition of the whole organism.

Moderate exercise training induces ROS-related adaptations to skeletal muscles.

Aim of the present work was the evaluation of the effects of moderate exercise training on 2 skeletal muscles differing in fibre-type composition, Tibialis Anterior (TA) and Soleus (SOL). Fibre adaptations, including their metabolic shift and mechanisms underlying proliferation and differentiation, oxidative stress markers, antioxidant and cytoprotective molecules, activity of Ca2+-handling molecules were examined. 6 male 2-month-old rats trained on a treadmill for 1 h/day, 3 days/week, for 14 weeks, reaching 30 m/min at the end of training.

Oxidative stress in the denervated muscle.

Following experimental hind limb denervation in rats, this study demonstrates that oxidative stress occurs and advances an hypothesis about its origin. In fact: (i) ROS are formed; (ii) membrane lipids are oxidized; (iii) oxidized ion channels and pumps may lead to increased [Ca(2+)](i); all the above mentioned events increase with denervation time. In the denervated muscle, (iv) mRNA abundance of cytoprotective and anti-oxidant proteins (Hsp70, Hsp27, Sod1, Catalase, Gpx1, Gpx4, Gstm1), as well as (v) SOD1 enzymatic activity and HSP70i protein increase; (vi) an unbalance in mitochondrial OXPHOS enzymes occurs, presumably leading to excess mitochondrial ROS production; (vii) increased cPLA2alpha expression (mRNA) and activation (increased [Ca(2+)](i)) may lead to increased hydroperoxides release.

Oxidative-induced membrane damage in diabetes lymphocytes: effects on intracellular Ca(2 +) homeostasis.

Oxidative stress is linked to several human diseases, including diabetes. However, the intracellular signal transduction pathways regulated by reactive oxygen species (ROS) remain to be established. Deleterious effects of ROS stem from interactions with various ion transport proteins such as ion channels and pumps, primarily altering Ca(2 +) homeostasis and inducing cell dysfunction.

Skeletal muscle is a primary target of SOD1G93A-mediated toxicity.

The antioxidant enzyme superoxide dismutase 1 (SOD1) is a critical player of the antioxidative defense whose activity is altered in several chronic diseases, including amyotrophic lateral sclerosis. However, how oxidative insult affects muscle homeostasis remains unclear. This study addresses the role of oxidative stress on muscle homeostasis and function by the generation of a transgenic mouse model expressing a mutant SOD1 gene (SOD1(G93A)) selectively in skeletal muscle.

Researchers misunderstand confidence intervals and standard error bars.

Little is known about researchers' understanding of confidence intervals (CIs) and standard error (SE) bars. Authors of journal articles in psychology, behavioral neuroscience, and medicine were invited to visit a Web site where they adjusted a figure until they judged 2 means, with error bars, to be just statistically significantly different (p < .05).

Sarcopenia is more than a muscular deficit.

Sarcopenia is a complex process that appears in aged muscle associated with a decrease in mass, strength, and velocity of contraction. This process is the result of many molecular, cellular and functional alterations. It has been suggested that sarcopenia may be triggered by reactive oxygen species (ROS) that have accumulated throughout one's lifetime.

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

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.

Evaluation of indices of skeletal muscle contraction in areas of referred hyperalgesia from an artificial ureteric stone in rats.

This study examined indices of skeletal muscle contraction in a rat model of referred muscle hyperalgesia from artificial ureteric calculosis [left oblique muscle (OE) for ipsilateral stone]. In specimens from the left versus right OE of stone-implanted female rats, a significant increase was found in membrane fluidity (P<0.01) and Ca(2+)-ATPase activity (P<0.

Age and sex influence on oxidative damage and functional status in human skeletal muscle.

A reduction in muscle mass, with consequent decrease in strength and resistance, is commonly observed with advancing age. In this study we measured markers of oxidative damage to DNA, lipids and proteins, some antioxidant enzyme activities as well Ca2+ transport in sarcoplasmic reticulum membranes in muscle biopsies from vastus lateralis of young and elderly healthy subjects of both sexes in order to evaluate the presence of age- and sex-related differences. We found a significant increase in oxidation of DNA and lipids in the elderly group, more evident in males, and a reduction in catalase and glutathione transferase activities.

Modifications of Ca2+ transport induced by glutathione in sarcoplasmic reticulum membranes of frog skeletal muscle.

The Ca2+ transport across the membrane of vesicles purified from the sarcoplasmic reticulum (SR) of frog skeletal muscle is modified by raising the concentration of the reduced form of glutathione (GSH). Passive release of Ca2+ is inhibited through the direct action of GSH on ryanodine receptors while active uptake is increased by a dose-dependent stimulation of Ca2+ pumps (Ca2+ -ATPase). These effects are physiological since the concentrations of GSH utilised (0.

Rapid desensitization of PC12 cells stimulated with high concentrations of extracellular S100.

Undifferentiated PC12 cells undergo apoptosis, via a calcium-induced calcium release mechanism, when the calcium-binding protein purified from bovine brain (native S100) is present in micromolar concentration in the medium. This process begins when S100 binds to specific membrane binding sites and involves up to 50% of the cell population. In the experiments reported here, we demonstrate that, by utilizing [3H]S100, the S100 protein can be displaced from its binding sites only during the first 10 min of incubation.

Sodium nitroprusside, a NO donor, modifies Ca2+ transport and mechanical properties in frog skeletal muscle.

Recently it has been hypothesized that, in skeletal muscle, NO produced directly by high-frequency stimulation could produce contraction through reactions with thiol groups on the sarcoplasmic reticulum (SR). However, a possible cGMP-mediated relaxing effect, similar to that seen in smooth muscle, has also been demonstrated. We used purified SR preparations and single fibres from frog fast muscles incubated with different concentrations of sodium nitroprusside (SNP) in this study.

Salicylates inhibit adhesion and transmigration of T lymphocytes by preventing integrin activation induced by contact with endothelial cells.

The inhibition of cyclooxygenase does not fully account for the spectrum of activities of nonsteroidal antiinflammatory drugs. It is evident, indeed, that regulation of inflammatory cell function may contribute in explaining some of the effects of these drugs. Tissue recruitment of T cells plays a key role in the development of chronic inflammation.

Nerve growth factor inhibits apoptosis induced by S-100 binding in neuronal PC12 cells.

When grown for seven days in a medium containing nerve growth factor (100 ng/ml), 10% horse serum and 5% fetal bovine serum PC12 cells stopped dividing, extended neurites and assumed a neuronal phenotype. Withdrawal of nerve growth factor from these cells resulted in loss of neurites and apoptotic changes in many cells. The apoptotic changes were exacerbated if the cells were also exposed to 1-2 microM S-100, a calcium binding protein purified from bovine brain.