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At least 1,099 records · Page 61Linked to original sources
PubMed1995

Calcium signalling initiated by CR1 (CD35) crosslinking is mediated by phagocyte Fc gamma receptors in cis.

We have examined the role of complement receptor type 1 (CR1; CD35) in generating intracellular signals in phagocytic cells, particularly human neutrophils. We find that crosslinking of CR1 alone fails to result in an increase in intracellular ionized calcium [Ca2+]i. However, IgG bound to CR1 is able to interact with Fc gamma receptors to stimulate increases in [Ca2+]i. By examining signals generated in mixed populations of cells, we determined that calcium increases are observed only when CR1 and Fc gamma receptors are engaged on the same cell. Functional interactions between complement receptors and receptors for immunoglobulin G may promote clearance of pathogenic bacteria and fungi that bind limited quantities of complement and IgG.

Animals↗
PubMed1998

Connexins regulate calcium signaling by controlling ATP release.

Forced expression of gap junction proteins, connexins, enables gap junction-deficient cell lines to propagate intercellular calcium waves. Here, we show that ATP secretion from the poorly coupled cell lines, C6 glioma, HeLa, and U373 glioblastoma, is potentiated 5- to 15-fold by connexin expression. ATP release required purinergic receptor-activated intracellular Ca2+ mobilization and was inhibited by Cl- channel blockers. Calcium wave propagation also was reduced by purinergic receptor antagonists and by Cl- channel blockers but insensitive to gap junction inhibitors. These observations suggest that cell-to-cell signaling associated with connexin expression results from enhanced ATP release and not, as previously believed, from an increase in intercellular coupling.

Adenosine Triphosphatases↗
PubMed2006

Calcium transients and calcium signalling during early neurogenesis in the amphibian embryo Xenopus laevis.

Development of the vertebrate embryonic nervous system is characterized by a cascade of signalling events. In Xenopus, the initial step in this cascade results from signals emanating from the dorsal mesoderm that divert the fate of the ectoderm from an epidermal to a neural lineage. These signals include extracellular antagonists of the bone morphogenetic protein (BMP). Experiments performed with isolated ectoderm suggest that epidermis is induced by BMP, whereas neural fates arise by default following BMP inhibition; however, we show that this mechanism is not sufficient for neural determination. Ca2+ imaging of intact Xenopus embryos reveals patterns of Ca2+ transients in the dorsal ectoderm but not in the ventral ectoderm. These increases in intracellular calcium concentration ([Ca2+](i)), which occur via the activation of dihydropyridine (DHP)-sensitive Ca2+ channels, are necessary and sufficient to orientate the ectodermal cells toward a neural fate. On the one hand, the treatments that antagonize the increase in [Ca2+](i), inhibit neuralization, while on the other hand, an artificial increase in [Ca2+](i), whatever its origin, neuralizes the ectoderm. Using these properties, we have constructed a subtractive cDNA library between untreated ectoderm and caffeine-treated ectoderm. The caffeine stimulates an increase in [Ca2+](i) and thus orientates the cells towards the neural pathway. We have identified early Ca2+ target genes expressed in neural territories. One of these genes, an arginine methyl transferase, controls the expression of the early proneural gene, Zic3. Here, we discuss an alternative model where Ca2+ plays a central regulatory role in early neurogenesis. This model integrates the activation of a Ca2+ -dependent signalling pathway due to an influx of Ca2+ through DHP-Ca2+ channels. While Ca2+ is required for neural determination, epidermal determination occurs when Ca2+ -dependent signalling pathways are inactive.

Animals↗
PubMed1998

Ristocetin-mediated interaction of human von Willebrand factor with platelet glycoprotein lb evokes a transient calcium signal: observations with Fura-PE3.

High shear stress in narrowed arteries causes von Willebrand factor (vWf) to bind to its platelet receptor, glycoprotein Ib (GpIb). This binding is reported to promote an increase in intracellular free calcium concentration ((Ca2+)i), which may be responsible for platelet activation. The present study examined the platelet (Ca2+)i signal that arises when ristocetin mediates vWf-GpIb binding. Platelet (Ca2+)i was monitored with Fura-PE3 (Vorndran C, Minta A, Poenie M. Biophys J 1995;69:2112-24), a new ratiometric calcium indicator. Fura-PE3 has calcium-binding characteristics (Kd = 146 nmol/L) and fluorescent properties similar to those of Fura-2. However, its zwitterionic nature ensured much slower extrusion from the platelet (0.2% per minute) than that for Fura-2. This eliminated one of the technical problems that seriously distorted previous measurements of vWf-induced changes in platelets (Ca2+)i. Design of a novel stirring arrangement avoided the other major problem, which is the tendency of platelet aggregates to settle to the bottom of the cuvette, beneath the detection zone of the spectrofluorometer. With Fura-PE3 and the new stirrer used in the present study, vWf-induced changes in (Ca2+)i could be measured reliably in aggregating platelets. Ristocetin-mediated vWf-GpIb binding induced a transient increase in platelet (Ca2+)i. This increase occurred after a significant lag phase; platelet (Ca2+)i rose gradually, followed by a decline to almost the resting level. Binding of vWf to platelet Gplb was responsible for the (Ca2+)i signal. A similar signal was found in the absence of extracellular calcium. These characteristics differ substantially from those described in previous reports, in which the vWf-induced rise in (Ca2+)i was attributed to calcium influx through channels in the plasma membrane. Data from those earlier studies, however, were severely distorted by indicator extrusion and loss of platelet aggregates. The present findings are a more accurate representation of the vWf-induced platelet (Ca2+]i signal.

Adult↗
PubMed2002

Induction of COX-2 and reactive gliosis by P2Y receptors in rat cortical astrocytes is dependent on ERK1/2 but independent of calcium signalling.

The present study has been aimed at characterizing the ATP/P2 receptor (and transductional pathways) responsible for the morphological changes induced in vitro by alphabetamethyleneATP on rat astrocytes obtained from cerebral cortex, a brain area highly involved in neurodegenerative diseases. Exposure of cells to this purine analogue resulted in elongation of cellular processes, an event reproducing in vitro a major hallmark of in vivo reactive gliosis. alphabetamethyleneATP-induced gliosis was prevented by the P2X/P2Y blocker pyridoxalphosphate-6-azophenyl-2'-4'-disulfonic acid, but not by the selective P2X antagonist 2',3'-O-(2,4,6-trinitrophenyl)-ATP, ruling out a role for ligand-gated P2X receptors. Conversely, the Gi/Go protein inactivator pertussis toxin completely prevented alphabetamethyleneATP-induced effects. No effects were induced by alphabetamethyleneATP on intracellular calcium concentrations. RT-PCR and western blot analysis showed that alphabetamethyleneATP-induced gliosis involves up-regulation of cyclooxygenase-2 (but not lipooxygenase). Also this effect was fully prevented by pyridoxalphosphate-6-azophenyl-2'-4'-disulfonic acid. Experiments with inhibitors of mitogen-activated protein kinases (MAPK) suggest that extracellular signal regulated protein kinases (ERK)1/2 mediate both cyclooxygenase-2 induction and the associated in vitro gliosis. These findings suggest that purine-induced gliosis involves the activation of a calcium-independent G-protein-coupled P2Y receptor linked to ERK1/2 and cyclooxygenase-2. Based on the involvement of cyclooxygenase-2 and inflammation in neurodegenerative diseases, these findings open up new avenues in the identification of novel biological targets for the pharmacological manipulation of neurodegeneration.

Adenosine Triphosphate↗
PubMed1999

Intracellular calcium signals measured with indo-1 in isolated skeletal muscle fibres from control and mdx mice.

1. Intracellular free calcium concentration ([Ca2+]i) was measured with the fluorescent indicator indo-1 in single skeletal fibres enzymatically isolated from the flexor digitorum brevis and interosseus muscles of control and dystrophic mdx C57BL/10 mice. Measurements were taken from a portion of fibre that was voltage clamped to allow detection of depolarization-induced changes in [Ca2+]i. 2. The mean (+/- s.e.m.) initial resting [Ca2+]i from all control and mdx fibres tested was 56 +/- 5 nM (n = 72) and 48 +/- 7 nM (n = 57), respectively, indicating no significant overall difference between the two groups. However, when comparing a batch of control and mdx fibres obtained from mice older than approximately 35 weeks, resting [Ca2+]i was significantly lower in mdx (16 +/- 4 nM, n = 11) than in control fibres (71 +/- 10 nM, n = 14). 3. Changes in [Ca2+]i elicited by short (5-35 ms) depolarizing pulses from -80 to 0 mV showed similar properties in control and mdx fibres. After a 5 ms duration pulse the mean time constant of [Ca2+]i decay was, however, significantly elevated in mdx as compared to control fibres, by a factor of 1.5-2. For longer pulses, no significant difference could be detected. 4. In response to 50 ms duration depolarizing pulses of various amplitudes the threshold for detection of an [Ca2+]i change and the peak [Ca2+]i reached for a given potential were similar in control and mdx fibres. 5. Overall results show that mdx skeletal muscle fibres are quite capable of handling [Ca2+]i at rest and in response to membrane depolarizations.

Age Factors↗
PubMed1998

Light irradiation of mouse spermatozoa: stimulation of in vitro fertilization and calcium signals.

Irradiation of mouse spermatozoa by 630 nm He-Ne laser was found to enhance the intracellular calcium levels and fertilizing potential of these cells. The effect of light on calcium transport and on fertilization rate was abrogated in the absence of Ca2+ during the irradiation time, indicating that the effect of light is Ca2+ dependent. The stimulatory effect of light on Ca2+ uptake was abolished in the presence of a voltage-dependent Ca(2+)-channel inhibitor nifedipine, indicating the involvement of a plasma membrane voltage-dependent Ca2+ channel. Furthermore, the stimulatory effect of light was completely inhibited by the mitochondrial uncoupler FCCP, indicating that laser irradiation might affect the mitochondrial Ca2+ transport mechanisms. A causal association between laser irradiation, reactive oxygen species (ROS) generation and sperm function was indicated by studies with ROS scavengers, superoxide dismutase (SOD) and catalase, and exogenous hydrogen peroxide. The SOD treatment, which enhanced H2O2 production, resulted in increased Ca2+ uptake and enhanced fertilization rate. On the other hand, catalase, which decomposes H2O2, impaired the light-induced stimulation in Ca2+ uptake and the fertilization rate. Taken together, the data suggest that H2O2 might be involved in the irradiation effects, and indeed laser irradiation enhances the production of H2O2 by spermatozoa. These results indicate that the effect of 630 nm He-Ne laser irradiation is mediated through the generation of H2O2 by the spermatozoa and that this effect plays a significant role in the augmentation of the sperm cells' capability to fertilize metaphase II-arrested eggs in vitro.

Animals↗
PubMedDate not supplied

Reactive oxygen species as mediators of calcium signaling by angiotensin II: implications in vascular physiology and pathophysiology.

Reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, and hydroxyl radical, and reactive nitrogen species, such as nitric oxide and peroxynitrite, are biologically relevant O2 derivatives increasingly being recognized as important in vascular biology through their oxidation/reduction (redox) potential. All vascular cell types produce ROS primarily via membrane-associated NAD(P)H oxidase. ROS influence vascular function by modulating contraction/dilation, cell growth, apoptosis/anoikis, migration, inflammation, and fibrosis. An imbalance in redox state where prooxidants overwhelm antioxidant capacity results in oxidative stress. Oxidative excess and associated oxidative damage are mediators of altered vascular tone and structural remodeling in many cardiovascular diseases. ROS elicit these effects by influencing intracellular signaling events. In addition to modulating protein tyrosine kinases, protein phosphatases, mitogen-activated protein kinases, and transcription factors, ROS are important regulators of intracellular Ca2+ homeostasis and RhoA/Rho kinase signaling. ROS increase vascular [Ca2+]i by stimulating inositol trisphosphate-mediated Ca2+ mobilization, by increasing cytosolic Ca2+ accumulation through sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibition, and by stimulating Ca2+ influx through Ca2+ channels. Increased ROS generation enhances Ca2+ signaling and up-regulates RhoA/Rho kinase, thereby altering vascular contractility and tone. The present review discusses the importance of ROS in angiotensin II signaling in vascular biology and focuses specifically on the role of oxidative stress in Ca2+ signaling in the vasculature.

Angiotensin II↗
PubMed2006

Discovery of a small-molecule inhibitor for kidney ADP-ribosyl cyclase: Implication for intracellular calcium signal mediated by cyclic ADP-ribose.

ADP-ribosyl cyclase (ADPR-cyclase) produces a Ca2+-mobilizing second messenger, cyclic ADP- ribose (cADPR), from beta-NAD+. A prototype of mammalian ADPR-cyclases is a lymphocyte antigen CD38. Accumulating evidence indicates that ADPR-cyclases other than CD38 are expressed in various cells and organs. In this study, we discovered a small molecule inhibitor of kidney ADPR-cyclase. This compound inhibited kidney ADPR-cyclase activity but not CD38, spleen, heart or brain ADPR-cyclase activity in vitro. Characterization of the compound in a cell-based system revealed that an extracellular calcium-sensing receptor (CaSR)- mediated cADPR production and a later long-lasting increase in intracellular Ca2+ concentration ([Ca2+]i) in mouse mesangial cells were inhibited by the pre-treatment with this compound. In contrast, the compound did not block CD3/TCR-induced cADPR production and the increase of [Ca2+]i in Jurkat T cells, which express CD38 exclusively. The long-lasting Ca2+ signal generated by both receptors was inhibited by pre-treatment with an antagonistic cADPR derivative, 8-Br-cADPR, indicating that the Ca2+ signal is mediated by the ADPR-cyclase metabolite, cADPR. Moreover, among structurally similar compounds tested, the compound inhibited most potently the cADPR production and Ca2+ signal induced by CaSR. These findings provide evidence for existence of a distinct ADPR-cyclase in the kidney and basis for the development of tissue specific inhibitors.

ADP-ribosyl Cyclase↗
PubMed2002

Mitochondrial stress-induced calcium signaling, phenotypic changes and invasive behavior in human lung carcinoma A549 cells.

We have investigated mechanisms of mitochondrial stress-induced phenotypic changes and cell invasion in tumorigenic but poorly invasive human pulmonary carcinoma A549 cells that were partly depleted of mitochondrial DNA (mtDNA). Depletion of mtDNA (genetic stress) caused a markedly lower electron transport-coupled ATP synthesis, loss of mitochondrial membrane potential, elevation of steady state [Ca(2+)](c), and notably induction of both glycolysis and gluconeogenic pathway enzymes. Markers of tumor invasion, cathepsin L and TGFbeta1, were overexpressed; calcium-dependent MAP kinases (ERK1 and ERK2) and calcineurin were activated. The levels of anti-apoptotic proteins Bcl2 and Bcl-X(L) were increased, and the cellular levels of pro-apoptotic proteins Bid and Bax were reduced. Both mtDNA-depleted cells (genetic stress) and control cells treated with carbonyl cyanide m-chlorophenylhydrazone (metabolic stress) exhibited higher invasive behavior than control cells in a Matrigel basement membrane matrix assay system. MtDNA-depleted cells stably expressing anti-sense cathepsin L RNA, TGFbeta1 RNA, or treated with specific inhibitors showed reduced invasion. Reverted cells with 80% of control cell mtDNA exhibited marker protein levels, cell morphology and invasive property closer to control cells. Our results suggest that the mitochondria-to-nucleus signaling pathway operating through increased [Ca(2+)](c) plays an important role in cancer progression and metastasis.

Adenocarcinoma↗
PubMed2006

Differential calcium signaling in dairy cows with specific CXCR1 genotypes potentially related to interleukin-8 receptor functionality.

Neutrophil migration and activation are critical components of innate immunity and are mediated by a variety of inflammatory mediators, which include interleukin-8 (IL-8) and epithelial-derived neutrophil activating peptide-78 (ENA-78). Limited knowledge on the expression of receptors for these inflammatory mediators (CXCR1 and CXCR2) in bovine, in addition to the association of a polymorphism (G-->C) in position +777 of the CXCR1 gene with impaired neutrophil function, prompted evaluation of CXCR1 and CXCR2 mRNA and protein expression, ligand binding affinity, and intracellular receptor signaling in neutrophils from cows with different CXCR1 genotypes. Initial observations revealed that overall IL-8 receptor numbers appeared to be lower in cows with a CC genotype compared to cows with a GG genotype. However, in the presence of SB225002, a CXCR2 inhibitor, CXCR1 affinity was about fivefold lower in cows with a CC genotype and may have resulted in an underestimation of receptor numbers in cows with this genotype. In addition, intracellular calcium ([Ca++]i) release was lower in cows with a CC genotype when cells were stimulated with IL-8 but not ENA-78. Furthermore, when neutrophils were stimulated with an optimal dose of IL-8 in the presence of SB225002, [Ca++]i release was lower in cows with a CC genotype, suggesting differential CXCR1 signaling among genotypes. These findings offer knowledge of the role that each of these receptors plays in the inflammatory response in the bovine and provide insight into the potential mechanisms that may be affected in neutrophils of cows with different CXCR1 genotypes.

Animals↗
PubMed1992

Calcium signaling and secretory responses in agonist-stimulated pituitary gonadotrophs.

In cultured pituitary gonadotrophs, gonadotropin-releasing hormone (GnRH) caused dose-dependent and biphasic increases in cytoplasmic calcium concentration ([Ca2+]i) and LH release. Both extra- and intracellular calcium pools participate in GnRH-induced elevation of [Ca2+]i and LH secretion. The spike phase of the [Ca2+]i response represents the primary signal derived predominantly from the rapid mobilization of intracellular Ca2+. In contrast, the prolonged phase of the Ca2+ signal depends exclusively on Ca2+ entry from the extracellular pool. The influx of Ca2+ occurs partially through dihydropyridine-sensitive calcium channels. Both [Ca2+]i and LH responses to increasing concentrations of GnRH occur over very similar time scales, suggesting that increasing degrees of receptor occupancy are transduced into amplitude-modulated Ca2+ responses, which in turn activate exocytosis in a linear manner. However, several lines of evidence indicated the complexity over the relationship between Ca2+ signaling and LH exocytosis. In contrast to [Ca2+]i measurements in cell suspension, single cell Ca2+ measurements revealed the existence of a more complicated pattern of Ca2+ response to GnRH, with a biphasic response to high agonist doses and prominent oscillatory responses to lower GnRH concentrations, with a log-linear correlation between GnRH dose and the frequency of Ca2+ spiking. In addition, analysis of the magnitudes of the [Ca2+]i and LH responses of gonadotrophs to a wide range of GnRH concentrations in the presence and absence of extracellular Ca2+, and to K+ and phorbol ester stimulation, showed non-linearity between these parameters with amplification of [Ca2+]i-mediated exocytosis. Studies on cell depleted of protein kinase C under conditions that did not change the LH pool suggested the participation of protein kinase C in this amplification, especially during the plateau phase of the secretory response to GnRH.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Activation of human neutrophils after contact with cellulose-based haemodialysis membranes: intracellular calcium signalling in single cells.

PURPOSE OF STUDY: In vitro contact of human leukocytes with cellulose-based dialysis membranes under complement-independent conditions results in activation of various leukocyte functions. To analyse signals involved in the mechanism of cell activation, we measured changes in cytosolic free calcium ([Ca2+]i) in individual human blood neutrophils (PMN) upon contact with flat sheet haemodialysis membranes. RESULTS: By confocal laser-scanning microscopy (CLSM), changes in [Ca2+]i were monitored in Fluo-3-labelled cells up to 10 min after contact with a regenerated cellulose (RC) membrane. Multiple [Ca2+]i transients were observed for cells in contact with RC; biostochastic analysis showed that up to 67% of the PMN responded with a high increase in [Ca2+]i, the rest were low- or non-responding cells. After contact with the new synthetic polycarbonate-polyether (PC-PE) membrane only non-responding cells were seen, indicating reduced cellular contact activation. The increase in [Ca2+]i of cells on RC could be inhibited by 5mM L-fucose. This monosaccharide was recently found to be present in cellulose-based polymers in picomolar concentrations. CONCLUSIONS: The data supports the hypothesis that dialysis-membrane-associated L-fucose residues participate in complement-independent leukocyte activation during haemodialysis therapy.

Biocompatible Materials↗