Echinocandins accelerate the particle transport velocity in the murine tracheal epithelium: dependency on intracellular Ca 2+ stores

The mucociliary clearance of lower airways is modulated by different physiologic stimuli and also by pathophysiologic agents like polluting substances or pharmaceutical molecules. In the present investigation, we measured the particle transport velocity (the PTV) of mouse tracheae as a surrogate for mucociliary clearance. In mouse tracheal preparations, we detected a sustained increase in the PTV under the application of the echinocandins caspofungin, anidulafungin, and micafungin. In further experiments we observed the effects of echinocandins on the PTV were dependent on intracellular Ca 2+ homeostasis. In Ca 2+ -free buffer solutions, the amplitude of the echinocandin-evoked rise in the PTV was significantly reduced relative to in the experiments in Ca 2+ -containing solutions. Depletion of intracellular Ca 2+ stores of the endoplasmic reticulum (ER) by caffeine completely prevented an increase in the PTV with subsequent caspofungin applications. Mitochondrial Ca 2+ stores seemed to be unaffected by echinocandin treatment. We also observed no altered generation of reactive oxygen species under the application of echinocandins as probable mediators of the PTV. Consequently, the observed echinocandin effects on the PTV depend upon the Ca 2+ influx and Ca 2+ contents of the ER. We assume that all three echinocandins may act intracellularly on ER Ca 2+ stores to activate Ca 2+ -dependent signal-transduction cascades, enhancing the PTV.

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Capacitative Ca2+ entry in agonist-induced pulmonary vasoconstriction

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.280.5.l870 ◽

2001 ◽

Vol 280 (5) ◽

pp. L870-L880 ◽

Cited By ~ 111

Author(s):

Sharon S. McDaniel ◽

Oleksandr Platoshyn ◽

Jian Wang ◽

Ying Yu ◽

Michele Sweeney ◽

...

Keyword(s):

Transient Receptor Potential ◽

Channel Blocker ◽

Receptor Potential ◽

Rt Pcr ◽

Pulmonary Vasoconstriction ◽

Store Depletion ◽

Intracellular Ca ◽

Gene Transcripts ◽

Transient Receptor ◽

Sustained Increase

Agonist-induced increases in cytosolic Ca2+ concentration ([Ca2+]cyt) in pulmonary artery (PA) smooth muscle cells (SMCs) consist of a transient Ca2+ release from intracellular stores followed by a sustained Ca2+ influx. Depletion of intracellular Ca2+ stores triggers capacitative Ca2+ entry (CCE), which contributes to the sustained increase in [Ca2+]cyt and the refilling of Ca2+ into the stores. In isolated PAs superfused with Ca2+-free solution, phenylephrine induced a transient contraction, apparently by a rise in [Ca2+]cyt due to Ca2+ release from the intracellular stores. The transient contraction lasted for 3–4 min until the Ca2+ store was depleted. Restoration of extracellular Ca2+ in the presence of phentolamine produced a contraction potentially due to a rise in [Ca2+]cyt via CCE. The store-operated Ca2+ channel blocker Ni2+ reduced the store depletion-activated Ca2+ currents, decreased CCE, and inhibited the CCE-mediated contraction. In single PASMCs, we identified, using RT-PCR, five transient receptor potential gene transcripts. These results suggest that CCE, potentially through transient receptor potential-encoded Ca2+ channels, plays an important role in agonist-mediated PA contraction.

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Subversion of host cell signalling by the protozoan parasiteLeishmania

Parasitology ◽

10.1017/s0031182005008139 ◽

2005 ◽

Vol 130 (S1) ◽

pp. S27-S35 ◽

Cited By ~ 61

Author(s):

D. J. GREGORY ◽

M. OLIVIER

Keyword(s):

Nitric Oxide ◽

Reactive Oxygen Species ◽

Cell Signalling ◽

Protein Tyrosine Phosphatases ◽

Innate Immune ◽

Signalling Pathways ◽

Oxygen Species ◽

Obligate Intracellular ◽

Intracellular Parasites ◽

Intracellular Ca

The protozoaLeishmaniaspp. are obligate intracellular parasites that inhabit the macrophages of their host. Since macrophages are specialized for the identification and destruction of invading pathogens, both directly and by triggering an innate immune response,Leishmaniahave evolved a number of mechanisms for suppressing some critical macrophage activities. In this review, we discuss how various species ofLeishmaniadistort the host macrophage's own signalling pathways to repress the expression of various cytokines and microbicidal molecules (nitric oxide and reactive oxygen species), and antigen presentation. In particular, we describe how MAP Kinase and JAK/STAT cascades are repressed, and intracellular Ca2+and the activities of protein tyrosine phosphatases, in particular SHP-1, are elevated.

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Lagrangian Solution for an Irrotational Progressive Water Wave Propagating on a Uniform Current

Journal of Atmospheric and Oceanic Technology ◽

10.1175/jtech-d-12-00171.1 ◽

2013 ◽

Vol 30 (4) ◽

pp. 825-845 ◽

Cited By ~ 4

Author(s):

Yang-Yih Chen ◽

Hsuan-Shan Chen ◽

Chu-Yu Lin ◽

Meng-Syue Li

Keyword(s):

Particle Velocity ◽

Particle Motion ◽

Particle Transport ◽

Water Wave ◽

Particle Trajectory ◽

Lagrangian Solution ◽

Transport Velocity ◽

Motion Period ◽

Fifth Order ◽

Horizontal Particle

Abstract Experiments are conducted to measure the motion properties of water particle for the progressive water wave propagation in the presence of following and adverse uniform currents. The experimental data are used to validate the fifth-order Lagrangian solution from Chen and Chen. The experimental results show that the measured data of the particle motion properties such as the b line (denoted as the line connecting the positions of consecutive particles of the same b label), the particle velocity, the particle transport velocity (drift velocity), the particle trajectory, the particle motion period, and the Lagrangian mean level are in close agreement with those of the fifth-order Lagrangian solution. The study also shows that the particle label could adopt the position coordinates of the particle as if it were in still water. The motion of the b line oscillates like wave motion: its wavelength is equal to the progressive wavelength and its wave velocity obeys the Doppler effect so the sum of the velocities of the progressive wave and current, the particle motion period, the Lagrangian mean level, and the particle transport velocity less current velocity are the same as for the case of pure progressive waves. For following currents, the shape of particle trajectory depends on the horizontal particle velocity at the trajectory trough. For adverse currents, the shape of particle trajectory depends on the horizontal particle velocity at the trajectory crest. For a description of the flow motion, the Lagrangian solution could be more effective and precise than the Eulerian solution.

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Capacitative Ca2+ entry is involved in cAMP synthesis in mouse parotid acini

AJP Cell Physiology ◽

10.1152/ajpcell.1998.274.3.c557 ◽

1998 ◽

Vol 274 (3) ◽

pp. C557-C565 ◽

Cited By ~ 31

Author(s):

Eileen L. Watson ◽

Zhiliang Wu ◽

Kerry L. Jacobson ◽

Daniel R. Storm ◽

Jean C. Singh ◽

...

Keyword(s):

Adenylyl Cyclase ◽

Time Course ◽

Phosphodiesterase Inhibitors ◽

Receptor Interaction ◽

Muscarinic Agonist ◽

Camp Accumulation ◽

Camp Synthesis ◽

Intracellular Ca ◽

Camp Levels ◽

Sustained Increase

Muscarinic receptor interaction leading to augmentation of isoproterenol-stimulated cAMP accumulation in mouse parotid acini involves Ca2+ (28). The effectiveness of capacitative Ca2+entry and intracellular Ca2+release on this response was determined in time course studies by using three independent tools to manipulate the free intracellular Ca2+ concentration: the muscarinic agonist carbachol, thapsigargin, and ionomycin. Time course studies revealed that Ca2+ release from intracellular stores by carbachol produced an early rapid increase (0.25–0.5 min) in stimulated cAMP levels, whereas capacitative Ca2+ entry resulted in a sustained increase in stimulated cAMP levels that was blocked by La3+. Capacitative Ca2+ entry, alone, was involved in thapsigargin and ionomycin augmentation of stimulated cAMP accumulation. The inability of phosphodiesterase inhibitors, 3-isobutyl-1-methylxanthine and milrinone, to prevent agonist augmentation of cAMP levels, as well as the finding that the type VIII adenylyl cyclase (ACVIII) is expressed in parotid acini, suggests that capacitative Ca2+ entry augments stimulated cAMP accumulation, at least in part, via activation of this adenylyl cyclase isoenzyme.

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Developmental plasticity of cardiac anoxia-tolerance in juvenile common snapping turtles ( Chelydra serpentina )

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2019.1072 ◽

2019 ◽

Vol 286 (1905) ◽

pp. 20191072 ◽

Cited By ~ 1

Author(s):

Ilan M. Ruhr ◽

Heather McCourty ◽

Afaf Bajjig ◽

Dane A. Crossley ◽

Holly A. Shiels ◽

...

Keyword(s):

Developmental Plasticity ◽

Hypoxia Tolerance ◽

Anoxia Tolerance ◽

Ros Production ◽

Oxygen Species ◽

Early Exposure ◽

Cellular Mechanisms ◽

Isolated Cardiomyocytes ◽

Intracellular Ca ◽

The Common

For some species of ectothermic vertebrates, early exposure to hypoxia during embryonic development improves hypoxia-tolerance later in life. However, the cellular mechanisms underlying this phenomenon are largely unknown. Given that hypoxic survival is critically dependent on the maintenance of cardiac function, we tested the hypothesis that developmental hypoxia alters cardiomyocyte physiology in a manner that protects the heart from hypoxic stress. To test this hypothesis, we studied the common snapping turtle, which routinely experiences chronic developmental hypoxia and exploits hypoxic environments in adulthood. We isolated cardiomyocytes from juvenile turtles that embryonically developed in either normoxia (21% O 2 ) or hypoxia (10% O 2 ), and subjected them to simulated anoxia and reoxygenation, while simultaneously measuring intracellular Ca 2+ , pH and reactive oxygen species (ROS) production. Our results suggest developmental hypoxia improves cardiomyocyte anoxia-tolerance of juvenile turtles, which is supported by enhanced myofilament Ca 2+ -sensitivity and a superior ability to suppress ROS production. Maintenance of low ROS levels during anoxia might limit oxidative damage and a greater sensitivity to Ca 2+ could provide a mechanism to maintain contractile force. Our study suggests developmental hypoxia has long-lasting effects on turtle cardiomyocyte function, which might prime their physiology for exploiting hypoxic environments.

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The inhibition of chloride intracellular channel 1 enhances Ca2+ and reactive oxygen species signaling in A549 human lung cancer cells

Experimental & Molecular Medicine ◽

10.1038/s12276-019-0279-2 ◽

2019 ◽

Vol 51 (7) ◽

Cited By ~ 2

Author(s):

Jae-Rin Lee ◽

Jong-Yoon Lee ◽

Hyun-Ji Kim ◽

Myong-Joon Hahn ◽

Jong-Sun Kang ◽

...

Keyword(s):

Lung Cancer ◽

Reactive Oxygen Species ◽

Cancer Cells ◽

Human Lung ◽

A549 Cells ◽

Human Lung Cancer ◽

Oxygen Species ◽

Human Lung Cancer Cells ◽

Intracellular Ca ◽

Intracellular Channel

AbstractChloride intracellular channel 1 (CLIC1) is a promising therapeutic target in cancer due to its intrinsic characteristics; it is overexpressed in specific tumor types and its localization changes from cytosolic to surface membrane depending on activities and cell cycle progression. Ca2+ and reactive oxygen species (ROS) are critical signaling molecules that modulate diverse cellular functions, including cell death. In this study, we investigated the function of CLIC1 in Ca2+ and ROS signaling in A549 human lung cancer cells. Depletion of CLIC1 via shRNAs in A549 cells increased DNA double-strand breaks both under control conditions and under treatment with the putative anticancer agent chelerythrine, accompanied by a concomitant increase in the p-JNK level. CLIC1 knockdown greatly increased basal ROS levels, an effect prevented by BAPTA-AM, an intracellular calcium chelator. Intracellular Ca2+ measurements clearly showed that CLIC1 knockdown significantly increased chelerythrine-induced Ca2+ signaling as well as the basal Ca2+ level in A549 cells compared to these levels in control cells. Suppression of extracellular Ca2+ restored the basal Ca2+ level in CLIC1-knockdown A549 cells relative to that in control cells, implying that CLIC1 regulates [Ca2+]i through Ca2+ entry across the plasma membrane. Consistent with this finding, the L-type Ca2+ channel (LTCC) blocker nifedipine reduced the basal Ca2+ level in CLIC1 knockdown cells to that in control cells. Taken together, our results demonstrate that CLIC1 knockdown induces an increase in the intracellular Ca2+ level via LTCC, which then triggers excessive ROS production and consequent JNK activation. Thus, CLIC1 is a key regulator of Ca2+ signaling in the control of cancer cell survival.

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Endothelin-1 increases intracellular Ca2+ in rabbit pulmonary artery smooth muscle cells through phospholipase C

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00131.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. H1551-H1559 ◽

Cited By ~ 15

Author(s):

Eun A. Ko ◽

Won Sun Park ◽

Jae-Hong Ko ◽

Jin Han ◽

Nari Kim ◽

...

Keyword(s):

Smooth Muscle ◽

Pulmonary Artery ◽

Smooth Muscle Cells ◽

Phospholipase C ◽

Muscle Cells ◽

Transient Increase ◽

Rabbit Pulmonary Artery ◽

Intracellular Ca ◽

Pulmonary Artery Smooth Muscle ◽

Sustained Increase

In freshly isolated rabbit pulmonary artery smooth muscle cells, endothelin (ET)-1 induced a transient increase in intracellular Ca2+ concentration ([Ca2+]i) followed by a return to the initial [Ca2+]i. This response was not abolished by the voltage-dependent Ca2+ channel blocker nicardipine or removal of Ca2+ from the bath solution but was inhibited by ryanodine and thapsigargin. This finding suggested that the increase in [Ca2+]i induced by ET-1 was attributable to release of Ca2+ from ryanodine- and inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ stores. The transient increase in [Ca2+]i induced by ET-1 was also inhibited by pretreatment with antagonists of ET type A and B (ETA and ETB) receptors (BQ-123 and BQ-788, respectively). Furthermore, the ETB receptor agonist IRL-1620 induced an increase in [Ca2+]i that was followed by a sustained increase in [Ca2+]i; the sustained increase in [Ca2+]i was blocked by nicardipine. Using the nystatin-perforated patch-clamp technique, we found that IRL-1620 caused an increase in Ca2+ current that was inhibited by addition of ET-1. ET-1 did not inhibit Ca2+ current when cells were pretreated with BQ-123. These results suggested that when both receptor types are activated, the opposing responses lead to abolition of the sustained [Ca2+]i increases induced by ETB receptor activation. Western blot analysis confirmed expression of ETA and ETB receptors. Finally, U-73122 inhibited the ET-1-induced [Ca2+]i increase, indicating that phospholipase C was involved in modulation of the ET-1-induced [Ca2+]i increase in rabbit pulmonary artery smooth muscle cells.

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The Subcellular Localization of the Receptor for Platelet-Activating Factor in Neutrophils Affects Signaling and Activation Characteristics

Clinical and Developmental Immunology ◽

10.1155/2013/456407 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

Emil Andréasson ◽

Karin Önnheim ◽

Huamei Forsman

Keyword(s):

Reactive Oxygen Species ◽

Plasma Membrane ◽

Subcellular Localization ◽

Platelet Activating Factor ◽

Subcellular Fractionation ◽

Oxygen Species ◽

High Affinity ◽

Formyl Peptide ◽

Intracellular Ca ◽

Vesicle Secretion

The localization in neutrophils, of the receptor for platelet-activating factor (PAFR), has been determined using subcellular fractionation and a receptor mobilization protocol. We show that the PAFR is expressed primarily in the plasma membrane. Although activation of neutrophils by PAF induces responses typical also of agonists that bind the formyl peptide receptors (FPR), known to be stored in mobilizable organelles, some quantitative as well as qualitative differences were observed when neutrophils were activated through these receptors. PAF is equipotent to fMLF (high affinity agonist for FPR1) to cleave off L-selectin and to induce granule/vesicle secretion but is more potent than fMLF to induce a rise in intracellular Ca2+. Similar to fMLF, PAF induced also a robust release of reactive oxygen species, but with higher EC50value and was less sensitive to a PI3K inhibitor compared to the fMLF response. Despite the lack of a granule localized storage pool of receptors, the PAF-induced superoxide production could be primed; receptor mobilization was, thus, not required for priming of the PAF response. The desensitized PAFR could not be reactivated, suggesting that distinct signaling pathways are utilized for termination of the responses triggered through FPR1 and PAFR.

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Excitotoxicity and overnutrition additively impair metabolic function and identity of pancreatic β-cells

10.2337/figshare.12170184.v2 ◽

2020 ◽

Author(s):

Ada Admin ◽

Anna B. Osipovich ◽

Jennifer S. Stancill ◽

Jean-Philippe Cartailler ◽

Karrie D.Dudek ◽

...

Keyword(s):

B Cell ◽

Cell Function ◽

Metabolic Stress ◽

Cell Junction ◽

Mitochondrial Energy Metabolism ◽

B Cell Function ◽

Intracellular Ca ◽

Metabolic Inflexibility ◽

The Impact ◽

Sustained Increase

A sustained increase in intracellular Ca2+ concentration (referred to herein as excitotoxicity), brought on by chronic metabolic stress, may contribute to pancreatic b-cell failure. To determine the additive effects of excitotoxicity and overnutrition on b-cell function and gene expression, we analyzed the impact of a high fat diet (HFD) on Abcc8 knock-out mice. Excitotoxicity caused b-cells to be more susceptible to HFD-induced impairment of glucose homeostasis, and these effects were mitigated by verapamil, a Ca2+ channel blocker. Excitotoxicity, overnutrition and the combination of both stresses caused similar but distinct alterations in the b-cell transcriptome, including additive increases in genes associated with mitochondrial energy metabolism, fatty acid b-oxidation and mitochondrial biogenesis, and their key regulator Ppargc1a. Overnutrition worsened excitotoxicity-induced mitochondrial dysfunction, increasing metabolic inflexibility and mitochondrial damage. In addition, excitotoxicity and overnutrition, individually and together, impaired both b-cell function and identity by reducing expression of genes important for insulin secretion, cell polarity, cell junction, cilia, cytoskeleton, vesicular trafficking, and regulation of b-cell epigenetic and transcriptional program. Sex had an impact on all b-cell responses, with male animals exhibiting greater metabolic stress-induced impairments than females. Together, these findings indicate that a sustained increase in intracellular Ca2+, by altering mitochondrial function and impairing b-cell identity, augments overnutrition-induced b-cell failure.

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Mechano-arrhythmogenicity is enhanced during late repolarisation in ischemia and driven by a TRPA1-, calcium-, and reactive oxygen species-dependent mechanism

10.1101/2021.08.20.457138 ◽

2021 ◽

Author(s):

Breanne Ashleigh Cameron ◽

T Alexander Quinn

Keyword(s):

Reactive Oxygen Species ◽

Ventricular Myocytes ◽

Reactive Oxygen ◽

Oxygen Species ◽

Cellular Mechanisms ◽

Sustained Activity ◽

Intracellular Ca ◽

Rabbit Ventricular Myocytes ◽

Induced Changes ◽

Dependent Mechanism

Background: Cardiac dyskinesis in regional ischemia results in arrhythmias through mechanically-induced changes in electrophysiology ('mechano-arrhythmogenicity') that involve ischemic alterations in voltage-calcium (Ca2+) dynamics, creating a vulnerable period (VP) in late repolarisation. Objective: To determine cellular mechanisms of mechano-arrhythmogenicity in ischemia and define the importance of the VP. Methods and Results: Voltage-Ca2+ dynamics were simultaneously monitored in rabbit ventricular myocytes by dual-fluorescence imaging to assess the VP in control and simulated ischemia (SI). The VP was longer in SI than in control (146±7 vs 54±8 ms; p<0.0001) and was reduced by blocking KATP channels with glibenclamide (109±6 ms; p<0.0001). Cells were rapidly stretched (10-18% increase in sarcomere length over 110-170 ms) with carbon fibres during diastole or the VP. Mechano-arrhythmogenicity, associated with stretch and release in the VP, was greater in SI than control (7 vs 1% of stretches induced arrhythmias; p<0.005) but was similar in diastole. Arrhythmias during the VP were more complex than in diastole (100 vs 69% had sustained activity; p<0.05). In the VP, incidence was reduced with glibenclamide (2%; p<0.05), by chelating intracellular Ca2+ (BAPTA; 2%; p<0.05), blocking mechano-sensitive TRPA1 (HC-030031; 1%; p<0.005), or by scavenging (NAC; 1%; p<0.005) or blocking reactive oxygen species (ROS) production (DPI; 2%; p<0.05). Ratiometric Ca2+ imaging revealed that SI increased diastolic Ca2+ (+9±1%, p<0.0001), which was not prevented by HC-030031 or NAC. Conclusion: In ischemia, mechano-arrhythmogenicity is enhanced specifically during the VP and is mediated by ROS, TRPA1, and Ca2+.

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