Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase.
AuthorsThastrup O, Cullen PJ, Drøbak BK, Hanley MR, Dawson AP
JournalProc Natl Acad Sci U S A
PubMed ID2138778
Thapsigargin, a tumor-promoting sesquiterpene lactone, discharges intracellular Ca2+ in rat hepatocytes, as it does in many vertebrate cell types. It appears to act intracellularly, as incubation of isolated rat liver microsomes with thapsigargin induces a rapid, dose-dependent release of stored Ca2+. The thapsigargin-releasable pool of microsomal Ca2+ includes the pools ... More
Muscarinic receptors modulate intracellular Ca(2+) concentration in hyaline cells of the chicken basilar papilla.
AuthorsLippe WR, Zirpel L, Stone JS
JournalJ Comp Physiol A Neuroethol Sens Neural Behav Physiol
PubMed ID12073083
Nonsensory hyaline cells border the sensory epithelium of the auditory end-organ (basilar papilla) in birds and reptiles. Their innervation by cochlear cholinergic efferent fibers and the presence of contractile proteins suggest that hyaline cells may actively regulate basilar membrane mechanics. The cholinergic pharmacology of hyaline cells was studied by measuring ... More
Transmission of cell stress from endoplasmic reticulum to mitochondria: enhanced expression of Lon protease.
AuthorsHori O, Ichinoda F, Tamatani T, Yamaguchi A, Sato N, Ozawa K, Kitao Y, Miyazaki M, Harding HP, Ron D, Tohyama M, M Stern D, Ogawa S
JournalJ Cell Biol
PubMed ID12082077
'The rat homologue of a mitochondrial ATP-dependent protease Lon was cloned from cultured astrocytes exposed to hypoxia. Expression of Lon was enhanced in vitro by hypoxia or ER stress, and in vivo by brain ischemia. These observations suggested that changes in nuclear gene expression (Lon) triggered by ER stress had ... More
Identification of ERSE-II, a new cis-acting element responsible for the ATF6-dependent mammalian unfolded protein response.
AuthorsKokame K, Kato H, Miyata T
JournalJ Biol Chem
PubMed ID11112790
'Herp is a 54-kDa membrane protein in the endoplasmic reticulum (ER). The mRNA expression level of Herp is increased by the accumulation of unfolded proteins in the ER. Transcriptional changes designed to deal with this type of ER stress is called the unfolded protein response (UPR). Most mammalian UPR-target genes ... More
Thapsigargin selectively rescues the trafficking defective LQT2 channels G601S and F805C.
AuthorsDelisle BP, Anderson CL, Balijepalli RC, Anson BD, Kamp TJ, January CT
JournalJ Biol Chem
PubMed ID12837749
'Several mutations in the human ether-a-go-go-related K+ channel gene (HERG or KCNH2) cause long QT syndrome (LQT2) by reducing the intracellular transport (trafficking) of the channel protein to the cell surface. Drugs that bind to and block HERG channels (i.e. E4031) rescue the surface expression of some trafficking defective LQT2 ... More
Baseline cytosolic Ca2+ oscillations derived from a non-endoplasmic reticulum Ca2+ store.
AuthorsMissiaen L, Van Acker K, Parys JB, De Smedt H, Van Baelen K, Weidema AF, Vanoevelen J, Raeymaekers L, Renders J, Callewaert G, Rizzuto R, Wuytack F
JournalJ Biol Chem
PubMed ID11514551
'Cytosolic Ca(2+) oscillations can be due to cycles of release and re-uptake of internally stored Ca(2+). To investigate the nature of these Ca(2+) stores, we expressed the Pmr1 Ca(2+) pump of Caenorhabditis elegans in COS-1 cells and pretreated the cells with thapsigargin to prevent Ca(2+) uptake by the sarco(endo)plasmic reticulum ... More
Focal exocytosis of VAMP3-containing vesicles at sites of phagosome formation.
AuthorsBajno L, Peng XR, Schreiber AD, Moore HP, Trimble WS, Grinstein S
JournalJ Cell Biol
PubMed ID10791982
'Phagocytosis involves the receptor-mediated extension of plasmalemmal protrusions, called pseudopods, which fuse at their tip to engulf a particle. Actin polymerizes under the nascent phagosome and may propel the protrusion of pseudopods. Alternatively, membrane extension could result from the localized insertion of intracellular membranes into the plasmalemma next to the ... More
Trp1, a candidate protein for the store-operated Ca(2+) influx mechanism in salivary gland cells.
AuthorsLiu X, Wang W, Singh BB, Lockwich T, Jadlowiec J, O'Connell B, Wellner R, Zhu MX, Ambudkar IS
JournalJ Biol Chem
PubMed ID10652333
'The trp gene family has been proposed to encode the store-operated Ca(2+) influx (SOC) channel(s). This study examines the role of Trp1 in the SOC mechanism of salivary gland cells. htrp1, htrp3, and Trp1 were detected in the human submandibular gland cell line (HSG). HSG cells stably transfected with htrp1alpha ... More
Cadherins mediate intercellular mechanical signaling in fibroblasts by activation of stretch-sensitive calcium-permeable channels.
AuthorsKo KS, Arora PD, McCulloch CA
JournalJ Biol Chem
PubMed ID11466312
'Cells in mechanically active environments form extensive, cadherin-mediated intercellular junctions that are important in tissue remodeling and differentiation. Currently, it is unknown whether adherens junctions in connective tissue fibroblasts transmit mechanical signals and coordinate multicellular adaptations to physical forces. We hypothesized that cadherins mediate intercellular mechanotransduction by activating calcium-permeable, stretch-sensitive ... More
Acetylcholine-induced calcium signaling and contraction of airway smooth muscle cells in lung slices.
AuthorsBergner A, Sanderson MJ
JournalJ Gen Physiol
PubMed ID11815668
'The Ca(2+) signaling and contractility of airway smooth muscle cells (SMCs) were investigated with confocal microscopy in murine lung slices (approximately 75-microm thick) that maintained the in situ organization of the airways and the contractility of the SMCs for at least 5 d. 10--500 nM acetylcholine (ACH) induced a contraction ... More
Stabilization of cortical actin induces internalization of transient receptor potential 3 (Trp3)-associated caveolar Ca2+ signaling complex and loss of Ca2+ influx without disruption of Trp3-inositol trisphosphate receptor association.
AuthorsLockwich T, Singh BB, Liu X, Ambudkar IS
JournalJ Biol Chem
PubMed ID11524429
'Ca(2+) influx via plasma membrane Trp3 channels is proposed to be regulated by a reversible interaction with inositol trisphosphate receptor (IP(3)R) in the endoplasmic reticulum. Condensation of the cortical actin layer has been suggested to physically disrupt this interaction and inhibit Trp3-mediated Ca(2+) influx. This study examines the effect of ... More
Unreliability of the cytochrome c-enhanced green fluorescent fusion protein as a marker of cytochrome c release in cells that overexpress Bcl-2.
AuthorsUnkila M, McColl KS, Thomenius MJ, Heiskanen K, Distelhorst CW
JournalJ Biol Chem
PubMed ID11489892
'A cytochrome c-enhanced green fluorescent protein chimera (cyt-c.EGFP) was used to monitor the release of cytochrome c from mitochondria in Bcl-2-negative and Bcl-2-positive MDA-MB-468 breast cancer cells. A comparison was made with the intracellular distribution of endogenous cytochrome c based on Western blotting of cell fractions and immunocytochemistry. The release ... More
Temperature-dependent arrest of neutrophil apoptosis. Failure of Bax insertion into mitochondria at 15 degrees C prevents the release of cytochrome c.
AuthorsPryde JG, Walker A, Rossi AG, Hannah S, Haslett C
JournalJ Biol Chem
PubMed ID10896657
'Apoptosis is essential for the resolution of neutrophilic inflammation. To define the mechanisms triggering the execution phase of apoptosis we developed and utilized a model in which culture of human neutrophils at 15 degrees C for 20 h arrested apoptosis and subsequent warming to 37 degrees C triggered a synchronous ... More
Direct measurement of free Ca in organelles of gastric epithelial cells.
AuthorsHofer AM, Machen TE
JournalAm J Physiol
PubMed ID7943242
'When loaded as the acetoxymethyl ester (AM) derivative, the fluorescent probe mag-fura 2 accumulates in both the cytoplasm and the subcellular compartments. The relatively high dissociation constant of this dye for Ca (53 microM) permits the measurement of changes in the free concentration of this ion in a variety of ... More
Androgens increase intracellular calcium concentration and inositol 1,4,5-trisphosphate and diacylglycerol formation via a pertussis toxin-sensitive G-protein.
AuthorsLieberherr M, Grosse B
JournalJ Biol Chem
PubMed ID8125934
'Bone is a target tissue of androgens, but the mechanisms by which they act on bone are still unclear. This study examines the early (5-60 s) effects of 1 pM to 1 microM testosterone on cytosolic free Ca2+ concentration ([Ca2+]i) and inositol 1,4,5-trisphosphate (InsP3) and diacyglycerol (DAG) formation in confluent ... More
Contribution of sustained Ca2+ elevation for nitric oxide production in endothelial cells and subsequent modulation of Ca2+ transient in vascular smooth muscle cells in coculture.
AuthorsWang Y, Shin WS, Kawaguchi H, Inukai M, Kato M, Sakamoto A, Uehara Y, Miyamoto M, Shimamoto N, Korenaga R, Ando J, Toyo-oka T
JournalJ Biol Chem
PubMed ID8621428
'To elucidate the intracellular Ca2+ (Ca2+i ) transient responsible for nitric oxide (NO) production in endothelial cells (ECs) and the subsequent Ca2+i reduction in vascular smooth muscle cells (VSMCs), we administrated four agonists with different Ca2+i-mobilizing mechanisms for both cells in iso- or coculture. We monitored the Ca2+i of both ... More
Determinants of metabotropic glutamate receptor-5-mediated Ca2+ and inositol 1,4,5-trisphosphate oscillation frequency. Receptor density versus agonist concentration.
'Diverse patterns of Ca(2+)(i) release differentially regulate Ca(2+)-sensitive enzymes and gene transcription, and generally the extent of agonist activation of phospholipase C-linked G protein-coupled receptors determines the type of Ca(2+) signal. We have studied global Ca(2+) oscillations arising through activation of the metabotropic glutamate receptor mGluR5a expressed in Chinese hamster ... More
An inositol 1,4,5-trisphosphate receptor-gated intracellular Ca(2+) store is involved in regulating sperm hyperactivated motility.
AuthorsHo HC, Suarez SS
JournalBiol Reprod
PubMed ID11673282
'Hyperactivated motility, a swimming pattern displayed by mammalian sperm in the oviduct around the time of ovulation, is essential to fertilization. Ca(2+) has been shown to be crucial for the initiation and maintenance of hyperactivated motility. Nevertheless, how Ca(2+) reaches the axoneme in the core of the flagellum to switch ... More
Fc gamma II receptor-mediated platelet activation induced by anti-CD9 monoclonal antibody opens Ca2+ channels which are distinct from those associated with Ca2+ store depletion.
AuthorsKuroda K, Ozaki Y, Qi R, Asazuma N, Yatomi Y, Satoh K, Nomura S, Suzuki M, Kume S
JournalJ Immunol
PubMed ID7594604
'Anti-human platelet CD9 mAb, NNKY1-19, induced platelet activation in a Fc gamma RII-dependent manner in terms of aggregation and secretion of intracellular granule contents. These responses were considerably suppressed by aspirin. [Ca2+]i elevation in the absence of extracellular Ca2+ ([Ca2+]e), which represents the amount of Ca2+ released from intracellular Ca2+ ... More
Tyrphostin A9 inhibits calcium release-dependent phosphorylations and calcium entry via calcium release-activated channel in Jurkat T cells.
'The mechanism by which calcium-depleted intracellular stores may trigger an external calcium influx through a calcium release-activated channel was investigated by analyzing the effects of several protein tyrosine kinase inhibitors on calcium movements in Jurkat T cells. Tyrphostin A9, an inhibitor of the kinase activity of the platelet-derived growth factor ... More
Farnesol inhibits L-type Ca2+ channels in vascular smooth muscle cells.
AuthorsRoullet JB, Luft UC, Xue H, Chapman J, Bychkov R, Roullet CM, Luft FC, Haller H, McCarron DA
JournalJ Biol Chem
PubMed ID9405427
'Earlier experiments with animal and human arteries have shown that farnesol, a natural 15-carbon (C15) isoprenoid, is an inhibitor of vasoconstriction (Roullet, J.-B., Xue, H., Chapman, J., McDougal, P., Roullet, C. M., and McCarron, D. A. (1996) J. Clin. Invest. 97, 2384-2390). We report here that farnesol reduced KCl- and ... More
Calcium signalling in granule neurones studied in cerebellar slices.
AuthorsKirischuk S, Voitenko N, Kostyuk P, Verkhratsky A
JournalCell Calcium
PubMed ID8653756
'The cytoplasmic free calcium concentration ([Ca2+]i) was studied in Fura-2/AM loaded granule neurones in acutely prepared cerebellar slices isolated from neonatal (6 days old) and adult (30 days old) mice. Bath application of elevated (10-50 mM) KCl-containing extracellular solutions evoked [Ca2+]i rise which was dependent on extracellular Ca2+. The K(+)-induced ... More
A new action of parathyroid hormone. receptor-mediated stimulation of extracellular acidification in human osteoblast-like SaOS-2 cells.
AuthorsBarrett MG, Belinsky GS, Tashjian AH
JournalJ Biol Chem
PubMed ID9334207
'The major physiological function of parathyroid hormone (PTH) is the maintenance of Ca2+/Pi homeostasis via the parathyroid hormone/parathyroid hormone-related protein receptor (PTHR) in kidney and bone. An important consequence of PTHR activation in bone is enhanced local acidification of the extracellular space. Agonist activation of some seven transmembrane-domain receptors increases ... More
Thimerosal potentiates Ca2+ release mediated by both the inositol 1,4,5-trisphosphate and the ryanodine receptors in sea urchin eggs. Implications for mechanistic studies on Ca2+ signaling.
AuthorsTanaka Y, Tashjian AH
JournalJ Biol Chem
PubMed ID8157654
'Two intracellular Ca2+ release pathways are modulated by Ca2+ itself, namely Ca(2+)-induced Ca2+ release (classical CICR), and Ca(2+)-sensitized inositol 1,4,5-trisphosphate (InsP3)-induced Ca2+ release (CSIICR). Both of these pathways are thought to be important in generating cytosolic Ca2+ oscillations. Caffeine and the sulfhydryl reagent thimerosal (TMS) are frequently used as selective ... More
Intracellular free Na+ in resting and activated A7r5 vascular smooth muscle cells.
AuthorsBorin ML, Goldman WF, Blaustein MP
JournalAm J Physiol
PubMed ID8333503
'Regulation of intracellular Na+ ([Na+]i) in cultured vascular smooth muscle cells (A7r5 line) was studied with Na(+)-sensitive fluorescent dye sodium-binding benzofuran isophthalate. Digital imaging microscopy was used to study single-cell fluorescence. Na+ was distributed uniformly in cytoplasm and nucleus; mean Na+ concentration in resting cells was 4.4 +/- 0.3 mM ... More
Fc receptor off-signal in the B cell involves apoptosis.
AuthorsAshman RF, Peckham D, Stunz LL
JournalJ Immunol
PubMed ID8683155
'By linking surface Ig to the FcR Fc gamma RII on the mouse B lymphocyte surface, whole anti-Ig has been shown to block cell cycle entry and subsequent Ab production, a phenomenon called the "Fc receptor off-signal." IL-4 or blocking Ab to Fc gamma RII, present with whole anti-Ig, restores ... More
Apparent cytosolic calcium gradients in T-lymphocytes due to fura-2 accumulation in mitochondria.
AuthorsQuintana A, Hoth M
JournalCell Calcium
PubMed ID15193858
'Fura-2 is the most common dye to measure cytosolic Ca2+ concentrations ([Ca2+]i). To facilitate simultaneous imaging of many cells while preserving their cytosolic environment, fura-2 is often loaded into the cytosol in its membrane-permeant ester form. It has been reported that small amounts of fura-2 accumulate in intracellular compartments, an ... More
Elevation of mitochondrial calcium by ryanodine-sensitive calcium-induced calcium release.
AuthorsNassar A, Simpson AW
JournalJ Biol Chem
PubMed ID10821828
'Calcium is an important regulator of mitochondrial function. Since there can be tight coupling between inositol 1,4, 5-trisphosphate-sensitive Ca(2+) release and elevation of mitochondrial calcium concentration, we have investigated whether a similar relationship exists between the release of Ca(2+) from the ryanodine receptor and the elevation of mitochondrial Ca(2+). Perfusion ... More
Cell type-specific modes of feedback regulation of capacitative calcium entry.
AuthorsLouzao MC, Ribeiro CM, Bird GS, Putney JW
JournalJ Biol Chem
PubMed ID8662975
'The Ca2+-ATPase inhibitor, thapsigargin, activated Ca2+ entry into pancreatic acinar cells, a process known as capacitative calcium entry. In cells loaded with the calcium chelator BAPTA, the transient Ca2+ release was blunted and the rise of [Ca2+]i on readdition of Ca2+ was slowed. However, the steady-state [Ca2+]i due to Ca2+ ... More
Increased internal Ca2+ mediates neural induction in the amphibian embryo.
AuthorsMoreau M, Leclerc C, Gualandris-Parisot L, Duprat AM
JournalProc Natl Acad Sci U S A
PubMed ID7809092
'The molecular mechanism of neural induction is still unknown and the identity of the natural inducer remains elusive. It has been suggested that both the protein kinase C and cAMP signal transduction pathways may be involved in mediating its action. Here we provide evidence that Ca2+ is implicated in the ... More
Thapsigargin activates a calcium influx pathway in the unfertilized mouse egg and suppresses repetitive calcium transients in the fertilized egg.
AuthorsKline D, Kline JT
JournalJ Biol Chem
PubMed ID1387638
'At fertilization, the sperm initiates development of the mouse egg by inducing a large transient increase in the intracellular Ca2+ concentration ([Ca2+]i), which is followed by repetitive transient increases in [Ca2+]i. To determine how the repetitive Ca2+ transients are produced, thapsigargin, an inhibitor of the endoplasmic reticulum Ca-ATPase, was used ... More
Lipopolysaccharide-mediated signal transduction through phospholipase D activation in monocytic cell lines.
AuthorsNatarajan V, Iwamoto GK
JournalBiochim Biophys Acta
PubMed ID8011674
'Lipopolysaccharide (LPS)-induced phospholipase D (PLD) activation was investigated in undifferentiated monocytic leukemic cell lines THP-1 and U-937. Treatment of THP-1 or U-937 cells labelled with [32P]orthophosphate, [32P]acyl GPC or [3H]alkyl GPC with LPS, in the presence of 0.5% ethanol, resulted in the accumulation of labelled phosphatidylethanol (PEt) through PLD activation. ... More
A hypo-osmotically induced increase in intracellular Ca2+ in lactating mouse mammary epithelial cells involving Ca2+ influx.
AuthorsSudlow AW, Burgoyne RD
JournalPflugers Arch
PubMed ID9049146
'Using a fluorescent Ca2+-sensitive dye, we studied the effect of hypo-osmotic stress on the intracellular free Ca2+ concentration ([Ca2+]i) in acini freshly isolated from lactating mouse mammary gland. The basal [Ca2+]i of mammary acini was unaffected by a 50% (v/v) dilution of suspensions with isotonic or hypertonic buffer, or after ... More
Nongenomic effects of androstenedione on human granulosa luteinizing cells.
AuthorsMachelon V, Nomé F, Tesarik J
JournalJ Clin Endocrinol Metab
PubMed ID9435453
'This study examines rapid (5-60 s) effects of androgens on the cytosolic free Ca2+ concentration ([Ca2+]i) in human granulosa lutenizing cells. Cells were obtained from human preovulatory follicles, and [Ca2+]i was measured with the use of the Ca(2+)-responsive fluorescent dye fluo-3. Molar concentrations between 100 pmol/L and 1 mumol/L androstenedione ... More
The COOH-terminal domain of Drosophila TRP channels confers thapsigargin sensitivity.
AuthorsSinkins WG, Vaca L, Hu Y, Kunze DL, Schilling WP
JournalJ Biol Chem
PubMed ID8621686
'Previous studies have shown that the Drosophila cation channels designated Trp and Trpl can be functionally expressed in Sf9 insect cells using baculovirus expression vectors. The trp gene encodes a Ca2+-permeable channel that is activated by thapsigargin, blocked by low micromolar Gd3+, and is relatively selective for Ca2+ versus Na+ ... More
Imaging of intracellular calcium stores in single permeabilized lens cells.
AuthorsChurchill GC, Louis CF
JournalAm J Physiol
PubMed ID9950770
'Intracellular Ca2+ stores in permeabilized sheep lens cells were imaged with mag-fura 2 to characterize their distribution and sensitivity to Ca2+-releasing agents. Inositol 1,4,5-trisphosphate (IP3) or cyclic ADP-ribose (cADPR) released Ca2+ from intracellular Ca2+ stores that were maintained by an ATP-dependent Ca2+ pump. The IP3 antagonist heparin inhibited IP3- but ... More
Phosphatidylinositol 4,5-bisphosphate functions as a second messenger that regulates cytoskeleton-plasma membrane adhesion.
AuthorsRaucher D, Stauffer T, Chen W, Shen K, Guo S, York JD, Sheetz MP, Meyer T
JournalCell
PubMed ID10660045
'Binding interactions between the plasma membrane and the cytoskeleton define cell functions such as cell shape, formation of cell processes, cell movement, and endocytosis. Here we use optical tweezers tether force measurements and show that plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) acts as a second messenger that regulates the adhesion energy ... More
Kinetics of thapsigargin-Ca(2+)-ATPase (sarcoplasmic reticulum) interaction reveals a two-step binding mechanism and picomolar inhibition.
AuthorsDavidson GA, Varhol RJ
JournalJ Biol Chem
PubMed ID7744817
'Thapsigargin is a high affinity inhibitor of sarco- and endoplasmic reticulum (SERCA) type ATPases. We have used kinetics to determine the dissociation constant of thapsigargin-sarcoplasmic reticulum Ca(2+)-ATPase interaction in the absence and presence of non-ionic detergent. The observed "off" rate constant was measured as 0.0052 s-1 at 26 degrees C ... More
The endogenous benzodiazepine receptor ligand ODN increases cytosolic calcium in cultured rat astrocytes.
AuthorsLamacz M, Tonon MC, Smih-Rouet F, Patte C, Gasque P, Fontaine M, Vaudry H
JournalBrain Res Mol Brain Res
PubMed ID8738163
'We have investigated the production of diazepam-binding inhibitor (DBI)-related peptides by astrocytes in primary culture and we have determined the effect of the octadecaneuropeptide DBI[33-50] (ODN) on the intracellular calcium concentration ([Ca2+]i) in astrocytes. Immunocytochemical labeling with antibodies against ODN showed that cultured astrocytes retain their ability to synthesize DBI ... More
Inhibition of Ca2+ entry by Ca2+ overloading of intracellular Ca2+ stores in human platelets.
AuthorsKimura M, Cho JH, Reeves JP, Aviv A
JournalJ Physiol
PubMed ID7527459
'1. This study examined the effect of overloading human platelet intracellular Ca2+ stores on the rate of agonist-evoked external Ca2+ entry. To overload the Ca2+ stores (presumably dense tubules), external Na(+)-dependent Ca2+ efflux via Na(+)-Ca2+ exchange was inhibited by pretreating the cells with ouabain or Na(+)-free medium. Ca2+ regulation was ... More
Superoxide anion impairs contractility in cultured aortic smooth muscle cells.
AuthorsKimura C, Cheng W, Hisadome K, Wang YP, Koyama T, Karashima Y, Oike M, Ito Y
JournalAm J Physiol Heart Circ Physiol
PubMed ID12063312
'We examined the effects of superoxide anion (O) generated by xanthine plus xanthine oxidase (X/XO) on the intracellular Ca(2+) concentration ([Ca(2+)](i)) and muscle contractility in cultured bovine aortic smooth muscle cells (BASMC). Cells were grown on collagen-coated dish for the measurement of [Ca(2+)](i). Pretreatment with X/XO inhibited ATP-induced Ca(2+) transient ... More
Separate analysis of nuclear and cytosolic Ca2+ concentrations in human umbilical vein endothelial cells.
AuthorsIkeda M, Ariyoshi H, Kambayashi J, Fujitani K, Shinoki N, Sakon M, Kawasaki T, Monden M
JournalJ Cell Biochem
PubMed ID8891901
'Ca2+ concentration inside human umbilical vein endothelial cells was studied separately in cytosol and nucleus by a confocal laser scanning microscopy using fluo-3. The in vivo calibration curve for cytosol and nucleus showed good linearity between fluorescence intensity and Ca2+ concentration in cytosol ([Ca2+]i) and nuclei ([Ca2+]n). After calibration, [Ca2+]n ... More
Phosphatidylinositol 3-kinase-dependent extracellular calcium influx is essential for CX(3)CR1-mediated activation of the mitogen-activated protein kinase cascade.
'Fractalkine, the first member of the CX(3)C chemokine family, induces leukocyte chemotaxis through activation of its high affinity receptor, CX(3)CR1. Like other chemokine receptors, CX(3)CR1 is coupled to a pertussis toxin-sensitive heterotrimeric G(i) protein, which is necessary for rapid rise in the concentration of intracellular calcium. Using a Chinese hamster ... More
Synthesis of a radioactive azido derivative of thapsigargin and photolabeling of the sarcoplasmic reticulum ATPase.
AuthorsHua S, Inesi G
JournalBiochemistry
PubMed ID9305979
'A thapsigargin C8-derivative (ZTG) was synthesized by acylating debutanoylthapsigargin with 4-azido[carboxyl-14C]benzoic acid. ZTG retains the inhibitory activity of thapsigargin (TG) with respect to the Ca2+ ATPase of sarcoplasmic reticulum (SR). Covalent ATPase labeling was obtained by photoactivation of the ZTG azido moiety under conditions optimized to reduce nonspecific association of ... More
An increase in intracellular calcium concentration that is induced by basolateral CO2 in rabbit renal proximal tubule.
AuthorsBouyer P, Zhou Y, Boron WF
JournalAm J Physiol Renal Physiol
PubMed ID12812914
'Working with isolated perfused S2 proximal tubules, we asked whether the basolateral CO2 sensor acts, in part, by raising intracellular Ca2+ concentration ([Ca2+]i), monitored with the dye fura 2 (or fura-PE3). In paired experiments, adding 5% CO2/22 mM HCO3- (constant pH 7.40) to the bath (basolateral) solution caused [Ca2+]i to ... More
Target-cell contact activates a highly selective capacitative calcium entry pathway in cytotoxic T lymphocytes.
AuthorsZweifach A
JournalJ Cell Biol
PubMed ID10662784
'Calcium influx is critical for T cell activation. Evidence has been presented that T cell receptor-stimulated calcium influx in helper T lymphocytes occurs via channels activated as a consequence of depletion of intracellular calcium stores, a mechanism known as capacitative Ca(2+) entry (CCE). However, two key questions have not been ... More
Overexpression of CALNUC (nucleobindin) increases agonist and thapsigargin releasable Ca2+ storage in the Golgi.
AuthorsLin P, Yao Y, Hofmeister R, Tsien RY, Farquhar MG
JournalJ Cell Biol
PubMed ID10209024
'We previously demonstrated that CALNUC, a Ca2+-binding protein with two EF-hands, is the major Ca2+-binding protein in the Golgi by 45Ca2+ overlay (Lin, P., H. Le-Niculescu, R. Hofmeister, J.M. McCaffery, M. Jin, H. Henneman, T. McQuistan, L. De Vries, and M. Farquhar. 1998. J. Cell Biol. 141:1515-1527). In this study ... More
Fc epsilon receptor mediated Ca2+ influx into mast cells is modulated by the concentration of cytosolic free Ca2+ ions.
AuthorsDar O, Pecht I
JournalFEBS Lett
PubMed ID1397260
'The relationship between the Fc epsilon receptor mediated stimulation of mast cells and the Ca2+ signal it induces were studied using thapsigargin (TG), a blocker of the endoplasmic reticulum Ca2+ pump. TG induced, in mucosal mast cells (RBL-2H3 line), a dose-dependent and an InsP3-independent increase in [Ca2+]i (from resting levels ... More
Interactions of dihydroxybenzenes with the Ca(2+)-ATPase: separate binding sites for dihydroxybenzenes and sesquiterpene lactones.
AuthorsKhan YM, Wictome M, East JM, Lee AG
JournalBiochemistry
PubMed ID7578042
'The Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum is inhibited by 2,5-di-tert-butyl-1,4-dihydroxybenzene (BHQ) and other hydrophobic 1,4-dihydroxybenzenes. Inhibitory potency increases on increasing substituent chain length from 2,5-dipropyl-1,4-dihydroxybenzene to 2,5-di-tert-amyl-1,4-dihydroxybenzene, the most potent inhibitor, but then decreases for 2,5-bis(7-methylheptyl)-1,4-dihydroxybenzene. Kinetic measurements are consistent with isomerization following the initial binding of BHQ to ... More
Inhibition of bradykinin- and thapsigargin-induced Ca2+ entry by tyrosine kinase inhibitors.
AuthorsLee KM, Toscas K, Villereal ML
JournalJ Biol Chem
PubMed ID7683685
'We examined the involvement of tyrosine kinase activity in the bradykinin (BK)-mediated signal transduction process. Immunoblots with anti-phosphotyrosine antibodies following BK stimulation of human fibroblasts showed tyrosine phosphorylation of specific proteins that could be inhibited by the tyrosine kinase inhibitors genistein and tyrphostin. Image analysis data from individual cells stimulated ... More
The relationship between depletion of intracellular Ca2+ stores and activation of Ca2+ current by muscarinic receptors in neuroblastoma cells.
AuthorsMathes C, Thompson SH
JournalJ Gen Physiol
PubMed ID8648300
'The relationship between the depletion of IP3-releasable intracellular Ca2+ stores and the activation of Ca(2+)-selective membrane current was determined during the stimulation of M1 muscarinic receptors in N1E-115 neuroblastoma cells. External Ca2+ is required for refilling Ca2+ stores and the voltage-independent, receptor-regulated Ca2+ current represents a significant Ca2+ source for ... More
Fibrinogen induces IL-8 synthesis in human neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine or leukotriene B(4).
AuthorsKuhns DB, Nelson EL, Alvord WG, Gallin JI
JournalJ Immunol
PubMed ID11509634
'Human exudative neutrophils have greatly increased stores of the neutrophil chemoattractant IL-8 compared with peripheral blood cells, but the mechanism for the increase is not defined. In this report, we show that treatment of peripheral blood neutrophils with the chemotactic peptide fMLP or with leukotriene B(4) or fibrinogen results in ... More
The FcgammaRII receptor triggers pp125FAK phosphorylation in platelets.
AuthorsHaimovich B, Regan C, DiFazio L, Ginalis E, Ji P, Purohit U, Rowley RB, Bolen J, Greco R
JournalJ Biol Chem
PubMed ID8663117
'Platelets express a single low affinity receptor for immunoglobulin, FcgammaRII, that triggers multiple cellular responses upon interaction with multivalent immune complexes. In this study we show that immobilized IgG is also a potent stimulant of platelet activation triggering adhesion, aggregation, massive dense granule secretion, and thromboxane production. Platelet adhesion to ... More
Calcium sensing receptor activation by a calcimimetic suggests a link between cooperativity and intracellular calcium oscillations.
AuthorsMiedlich S, Gama L, Breitwieser GE
JournalJ Biol Chem
PubMed ID12399473
'Activation of the calcium sensing receptor (CaR) by small increments in extracellular calcium (Ca(2+)(e)) induces intracellular calcium (Ca(2+)(i)) oscillations that are dependent on thapsigargin-sensitive intracellular calcium stores. Phenylalkylamines such as NPS R-568 are allosteric modulators (calcimimetics) that activate CaR by increasing the apparent affinity of the receptor for calcium. We ... More
Mechanisms of Hydrogen Peroxide-Induced Increase in Intracellular Calcium in Cardiomyocytes.
'BACKGROUND: Hydrogen peroxide (H(2)O(2)) in high concentrations has been implicated in heart dysfunction attributable to ischemia-reperfusion. Although H(2)O(2) is also known to increase the intracellular concentration of Ca(2+) ([Ca(2+)](i)) in cardiomyocytes, the mechanisms for such a change are not clear. In this study, the sources and mechanisms of increase in ... More
Signal transduction in Jurkat T lymphocytes. Evidence for early Ca2+ movements between the cytoplasm and the nucleoplasm in activated cells.
AuthorsGagné D, Ahnadi CE, Martel J, Payet MD, Dupuis G
JournalJ Leukoc Biol
PubMed ID9400830
'Spatial analyses of the distribution of Ca2+ in resting and activated T and B lymphocytes have shown that the bulk of increased [Ca2+]i appears to be associated with the nuclear region. These observations suggest that Ca2+ is released from the perinuclear space or that it diffuses to the nucleoplasm, or ... More
Regulated trafficking of the human dopamine transporter. Clathrin-mediated internalization and lysosomal degradation in response to phorbol esters.
AuthorsDaniels GM, Amara SG
JournalJ Biol Chem
PubMed ID10585462
'The dopamine transporter plays an essential role in the modulation of dopaminergic neurotransmission by mediating the reuptake of dopamine into presynaptic neurons. In cells expressing the dopamine transporter, activation of protein kinase C by phorbol esters results in a significant reduction in dopamine uptake. This phorbol ester-mediated inhibition of dopamine ... More
Nuclear calcium transport and the role of calcium in apoptosis.
AuthorsNicotera P, Zhivotovsky B, Orrenius S
JournalCell Calcium
PubMed ID7820847
'The last decade has been the rapid development of research investigating the molecular mechanisms whereby hormones, peptide growth factors and cytokines regulate cell metabolism, differentiation and proliferation. One general signalling mechanism used to transfer the information delivered by agonists into appropriate intracellular compartments involves the rapid Ca2+ redistribution throughout the ... More
Depletion of intracellular Ca2+ stores activates nitric-oxide synthase to generate cGMP and regulate Ca2+ influx.
AuthorsXu X, Star RA, Tortorici G, Muallem S
JournalJ Biol Chem
PubMed ID7513692
'The mechanism of activation of the agonist-stimulated Ca2+ entry pathway in the plasma membrane is not known. To determine the role of nitric-oxide synthase (NOS) and cGMP in the regulation of this pathway, we used intact and streptolysin O (SLO)-permeable pancreatic acini and measured the relationship between Ca2+ release from ... More
Caldesmon inhibits nonmuscle cell contractility and interferes with the formation of focal adhesions.
AuthorsHelfman DM, Levy ET, Berthier C, Shtutman M, Riveline D, Grosheva I, Lachish-Zalait A, Elbaum M, Bershadsky AD
JournalMol Biol Cell
PubMed ID10512853
'Caldesmon is known to inhibit the ATPase activity of actomyosin in a Ca(2+)-calmodulin-regulated manner. Although a nonmuscle isoform of caldesmon is widely expressed, its functional role has not yet been elucidated. We studied the effects of nonmuscle caldesmon on cellular contractility, actin cytoskeletal organization, and the formation of focal adhesions ... More
Dissociation of platelet-activating factor production and arachidonate release by the endomembrane Ca(2+)-ATPase inhibitor thapsigargin. Evidence for the involvement of a Ca(2+)-dependent route of priming in the production of lipid mediators by human polymorphonuclear leukocytes.
AuthorsGarcia Rodriguez C, Montero M, Alvarez J, García-Sancho J, Sánchez Crespo M
JournalJ Biol Chem
PubMed ID8227034
'The production of platelet-activating factor (PAF) and the release of [3H]arachidonate were studied in human polymorphonuclear leukocytes (PMN) stimulated with thapsigargin, an inhibitor of endomembrane Ca(2+)-ATPase. Concentrations of thapsigargin as low as 10-25 nM primed PMN for both PAF production and [3H]arachidonate release in response to the chemotactic peptide (fMLP), ... More
Thapsigargin potentiates histamine-stimulated HCl secretion in gastric parietal cells but does not mimic cholinergic responses.
AuthorsChew CS, Petropoulos AC
JournalCell Regul
PubMed ID1848793
'The role of calcium in control of HCl secretion by the gastric parietal cell was examined using a recently available intracellular calcium-releasing agent, thapsigargin, which has been shown, in some cell types, to induce sustained elevation of intracellular calcium ([Ca2+]i), an action that appears to be independent of inositol lipid ... More
Arachidonic acid inhibits capacitative calcium entry in rat thymocytes and human neutrophils.
AuthorsAlonso-Torre SR, García-Sancho J
JournalBiochim Biophys Acta
PubMed ID9315617
'Emptying the intracellular Ca2+ stores by treatment with the endomembrane Ca2+-ATPase inhibitor thapsigargin activates capacitative Ca2+ entry (CCE). This can be evidenced in fura-2-loaded cells by an increase of [Ca2+]i or by an acceleration of Mn2+ entry. Micromolar concentrations of arachidonic acid inhibited CCE induced by treatment with thapsigargin in ... More
Evidence for cadmium mobilization of intracellular calcium through a divalent cation receptor in renal distal epithelial A6 cells.
AuthorsFaurskov B, Bjerregaard HF
JournalPflugers Arch
PubMed ID12397385
'The effect of Cd(2+) on intracellular Ca(2+) homeostasis was examined in renal epithelial A6 cells loaded with Fura-2. Cd(2+) (10 microM to 1 mM) produced a transient spike in cytosolic Ca(2+) in a dose-dependent manner. The phospholipase C inhibitor U73122 and the cation receptor agonist, neomycin, both diminish Cd(2+)-evoked increase ... More
Induction of cytosolic Ca2+ elevation mediated by Mas-7 occurs through membrane pore formation.
AuthorsSuh BC, Song SK, Kim YK, Kim KT
JournalJ Biol Chem
PubMed ID8955110
'Mas-7, a mastoparan derivative, induces elevation of intracellular free Ca2+ concentration ([Ca2+]i) along two independent pathways. The minor contribution occurs via phospholipase C activation and is negatively regulated by treatment with phorbol 12-myristate 13-acetate, a protein kinase C activator. The major contribution involves plasma membrane pores allowing not only Ca2+, ... More
Thapsigargin-induced increase in cytoplasmic Ca2+ concentration and aldosterone production in rat adrenal glomerulosa cells: interaction with potassium and angiotensin-II.
'Thapsigargin (Tg), a microsomal Ca2+ pump inhibitor, dose-dependently increases the cytoplasmic Ca2+ concentration and aldosterone production without having any striking effect on the formation of inositol phosphates in isolated rat adrenal glomerulosa cells. The interaction of Tg with the major Ca2(+)-mediated stimuli of glomerulosa cells on aldosterone production was also ... More
Nitric oxide disrupts Ca2+ homeostasis in hippocampal neurons.
AuthorsBrorson JR, Sulit RA, Zhang H
JournalJ Neurochem
PubMed ID8978714
'Nitric oxide has been recognized in recent years as an important mediator of neuronal toxicity, which in many cases involves alterations of the cytoplasmic Ca2+ concentration ([Ca2+]i). In [Ca2+]i fluorimetric experiments on cultured hippocampal neurons, the nitric oxide-releasing agent S-nitrosocysteine produced a delayed rise in [Ca2+]i over a 20-min exposure, ... More
L-type Ca2+ channels and K+ channels specifically modulate the frequency and amplitude of spontaneous Ca2+ oscillations and have distinct roles in prolactin release in GH3 cells.
AuthorsCharles AC, Piros ET, Evans CJ, Hales TG
JournalJ Biol Chem
PubMed ID10066818
'GH3 cells showed spontaneous rhythmic oscillations in intracellular calcium concentration ([Ca2+]i) and spontaneous prolactin release. The L-type Ca2+ channel inhibitor nimodipine reduced the frequency of Ca2+ oscillations at lower concentrations (100nM-1 microM), whereas at higher concentrations (10 microM), it completely abolished them. Ca2+ oscillations persisted following exposure to thapsigargin, indicating ... More
Ligand-affected shift of Na+/H+ exchange pHi set point in human blood platelets, rapidly revealed by a novel approach.
AuthorsLivne AA, Aharonovitz O
JournalBiochim Biophys Acta
PubMed ID1591268
'The Na+/H+ exchange time-course of BCECF-loaded human platelets, suspended in isotonic media containing NaCl and sodium propionate and activated by intracellular acidification, was measured spectrofluorimetrically. Sequential alkalinization rates decline exponentially as a function of the changing intracellular pH (pHi) and its linear expression (log rate vs. pHi) extrapolates reproducibly to ... More
alpha(2A)-adrenergic receptor stimulation potentiates calcium release in platelets by modulating cAMP levels.
'alpha(2A)-Adrenergic receptor-mediated Ca(2+) signaling and integrin alpha(IIb)beta(3) exposure were investigated in human platelets under conditions where indirect, thromboxane- or ADP-mediated effects were absent. The alpha(2)-adrenergic receptor agonists, UK14304 and epinephrine (EPI), were unable to raise cytosolic levels of inositol 1,4,5-trisphosphate (InsP(3)) or Ca(2+) but potentiated the [Ca(2+)](i) rises evoked by ... More
Ca2+-dependent production and release of IL-8 in human neutrophils.
AuthorsKuhns DB, Young HA, Gallin EK, Gallin JI
JournalJ Immunol
PubMed ID9780210
'IL-8, a potent neutrophil chemoattractant that is elevated about 200-fold in exudative neutrophils isolated from localized inflammatory sites in vivo, is thought to play a major role in recruitment of neutrophils to inflammatory sites. Incubation of peripheral blood neutrophils with thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-sequestering-ATPase, causes a ... More
Evidence against a major role for Ca2+ in hypoxia-induced gene expression in human hepatoma cells (Hep3B).
AuthorsMetzen E, Fandrey J, Jelkmann W
JournalJ Physiol
PubMed ID10358107
'1. The human hepatoma cell line Hep3B is a widely used model for studies of hypoxia-related gene expression. Cytosolic free calcium concentration ([Ca2+]i) has been implicated in cellular oxygen-sensing processes. We investigated whether calcium ions have a significant impact on the production of erythropoietin (EPO) and vascular endothelial growth factor ... More
Secretagogues modulate the calcium concentration in the endoplasmic reticulum of insulin-secreting cells. Studies in aequorin-expressing intact and permeabilized ins-1 cells.
AuthorsMaechler P, Kennedy ED, Sebö E, Valeva A, Pozzan T, Wollheim CB
JournalJ Biol Chem
PubMed ID10212237
'The precise regulation of the Ca2+ concentration in the endoplasmic reticulum ([Ca2+]er) is important for protein processing and signal transduction. In the pancreatic beta-cell, dysregulation of [Ca2+]er may cause impaired insulin secretion. The Ca2+-sensitive photoprotein aequorin mutated to lower its Ca2+ affinity was stably expressed in the endoplasmic reticulum (ER) ... More
Formyl peptide receptor signaling in HL-60 cells through sphingosine kinase.
AuthorsAlemany R, Meyer zu Heringdorf D, van Koppen CJ, Jakobs KH
JournalJ Biol Chem
PubMed ID9933590
'Sphingosine-1-phosphate (SPP) produced from sphingosine by sphingosine kinase has recently been reported to act as intracellular second messenger for a number of plasma membrane receptors. In the present study, we investigated whether the sphingosine kinase/SPP pathway is involved in cellular signaling of the Gi protein-coupled formyl peptide receptor in myeloid ... More
The endoplasmic reticulum can act as a functional Ca2+ store in all subcellular regions of the pancreatic acinar cell.
Authorsvan de Put FH, Elliott AC
JournalJ Biol Chem
PubMed ID9346920
'Stimulation of pancreatic acinar cells raises [Ca2+]i via Ca2+ release from inositol-1,4,5-trisphosphate (InsP3)-sensitive intracellular Ca2+ stores, generally considered to reside within the endoplasmic reticulum (ER). However, with physiological doses of cholinergic agonists, the [Ca2+]i increase is localized to the apical (secretory) pole of the cell, leading to suggestions that zymogen ... More
Ca(2+) as second messenger in PTTH-stimulated prothoracic glands of the silkworm, Bombyx mori.
AuthorsBirkenbeil H, Dedos SG
JournalInsect Biochem Mol Biol
PubMed ID12429114
'Measurements of Ca(2+) influx and [Ca(2+)](i) changes in Fura-2/AM-loaded prothoracic glands (PGs) of the silkworm, Bombyx mori, were used to identify Ca(2+) as the actual second messenger of the prothoracicotropic hormone (PTTH) of this insect. Dose-dependent increases of [Ca(2+)](i) in PG cells were recorded in the presence of recombinant PTTH ... More
Effects of cell swelling on intracellular calcium and membrane currents in bovine articular chondrocytes.
AuthorsYellowley CE, Hancox JC, Donahue HJ
JournalJ Cell Biochem
PubMed ID12111998
'Chondrocytes experience a dynamic extracellular osmotic environment during normal joint loading when fluid is forced from the matrix, increasing the local proteoglycan concentration and therefore the ionic strength and osmolarity. To exist in such a challenging environment, chondrocytes must possess mechanisms by which cell volume can be regulated. In this ... More
cAMP-dependent protein kinase induces cAMP-response element-binding protein phosphorylation via an intracellular calcium release/ERK-dependent pathway in striatal neurons.
AuthorsZanassi P, Paolillo M, Feliciello A, Avvedimento EV, Gallo V, Schinelli S
JournalJ Biol Chem
PubMed ID11139572
'Activation of the cAMP-dependent protein kinase A (PKA) pathway may induce cAMP-response element-binding protein (CREB) phosphorylation either directly or via cross-talk mechanisms with other signal transduction pathways. In this study, we have investigated in striatal primary cultures the mechanism by which activation of the cAMP/PKA-dependent pathway leads to CREB phosphorylation ... More
Effect of glucose and deoxyglucose on cytoplasmic [Ca2+] in Ehrlich ascites tumor cells.
AuthorsTeplova VV, Bogucka K, Czyz A, Evtodienko YV, Duszynski J, Wojtczak L
JournalBiochem Biophys Res Commun
PubMed ID8250873
'Concentration of free cytoplasmic Ca2+ ([Ca2+]i) in Ehrlich ascites tumor cells, measured using fura-2, amounted to 170-300 nM and was increased by 50-160 nM after addition of 10 mM D-glucose or D-2-deoxyglucose but not 3-O-methylglucose at pH 7.4. In the range of external pH between 6.8 and 7.8 the increase ... More
Depletion of intracellular calcium stores activates smooth muscle cell calcium-independent phospholipase A2. A novel mechanism underlying arachidonic acid mobilization.
AuthorsWolf MJ, Wang J, Turk J, Gross RW
JournalJ Biol Chem
PubMed ID8999823
'Herein we present multiple lines of evidence which demonstrate that depletion of internal calcium stores is both necessary and sufficient for the activation of calcium-independent phospholipase A2 during arginine vasopressin (AVP)-mediated mobilization of arachidonic acid in A-10 smooth muscle cells. First, AVP-induced [3H]arachidonic acid release was independent of increases in ... More
The role of luminal Ca2+ in the generation of Ca2+ waves in rat ventricular myocytes.
AuthorsLukyanenko V, Subramanian S, Gyorke I, Wiesner TF, Gyorke S
JournalJ Physiol
PubMed ID10373699
'1. We used confocal Ca2+ imaging and fluo-3 to investigate the transition of localized Ca2+ releases induced by focal caffeine stimulation into propagating Ca2+ waves in isolated rat ventricular myocytes. 2. Self-sustaining Ca2+ waves could be initiated when the cellular Ca2+ load was increased by elevating the extracellular [Ca2+] ([Ca2+]o) ... More
Requirement of the inositol trisphosphate receptor for activation of store-operated Ca2+ channels.
'The coupling mechanism between endoplasmic reticulum (ER) calcium ion (Ca2+) stores and plasma membrane (PM) store-operated channels (SOCs) is crucial to Ca2+ signaling but has eluded detection. SOCs may be functionally related to the TRP family of receptor-operated channels. Direct comparison of endogenous SOCs with stably expressed TRP3 channels in ... More
Versatile regulation of cytosolic Ca2+ by vanilloid receptor I in rat dorsal root ganglion neurons.
AuthorsLiu M, Liu MC, Magoulas C, Priestley JV, Willmott NJ
JournalJ Biol Chem
PubMed ID12454015
'Analysis of small dorsal root ganglion (DRG) neurons revealed novel functions for vanilloid receptor 1 (VR1) in the regulation of cytosolic Ca(2+). The VR1 agonist capsaicin induced Ca(2+) mobilization from intracellular stores in the absence of extracellular Ca(2+), and this release was inhibited by the VR1 antagonist capsazepine but was ... More
The HIV Nef protein alters Ca(2+) signaling in myelomonocytic cells through SH3-mediated protein-protein interactions.
'Human immunodeficiency virus Nef plays an important role in AIDS pathogenesis. In addition to the well known down-regulation of cell surface receptors (CD4, MHCI), Nef is able to alter cellular signaling. Of particular interest for this study is the ability of Nef to bind with a very high affinity to ... More
'Parathyroid hormone secretion is exquisitely sensitive to small changes in serum Ca2+ concentration, and these responses are transduced via the Ca2+-sensing receptor (CaR). We utilized heterologous expression in HEK-293 cells to determine the effects of small, physiologically relevant perturbations in extracellular Ca2+ on CaR signaling via phosphatidylinositol-phospholipase C, using changes ... More
Significance of Na/Ca exchange for Ca2+ buffering and electrical activity in mouse pancreatic beta-cells.
AuthorsGall D, Gromada J, Susa I, Rorsman P, Herchuelz A, Bokvist K
JournalBiophys J
PubMed ID10096898
'We have combined the patch-clamp technique with microfluorimetry of the cytoplasmic Ca2+ concentration ([Ca2+]i) to characterize Na/Ca exchange in mouse beta-cells and to determine its importance for [Ca2+]i buffering and shaping of glucose-induced electrical activity. The exchanger contributes to Ca2+ removal at [Ca2+]i above 1 microM, where it accounts for ... More
Thapsigargin and di-tert-butylhydroquinone induce synergistic stimulation of DNA synthesis with phorbol ester and bombesin in Swiss 3T3 cells.
AuthorsCharlesworth A, Rozengurt E
JournalJ Biol Chem
PubMed ID7798254
'The specific inhibitors of the endoplasmic reticulum Ca2+ pump, thapsigargin and 2,5-di-tert-butylhydroquinone (DBHQ), stimulated reinitiation of DNA synthesis in synergy with either phorbol 12,13-dibutyrate or bombesin in Swiss 3T3 cells. Maximum stimulation was achieved at 0.5 nM thapsigargin and 7.5 microM DBHQ. Kinetics of [3H]thymidine incorporation were consistent with exit ... More
Differences in intracellular CA2+ stores of submandibular cells of adult and newborn rats.
'The intracellular Ca2+ stores of submandibular acinar cells of adult and newborn rats were compared by measuring changes in cytosolic Ca2+ ([Ca2+]i) with the Ca2+-sensitive fluorescent probe, fura-2, in intact cells and 45Ca2+ release in permeabilized cells. In cells of adult rats, acetylcholine (ACh) and thapsigargin (TG) elicited, respectively, a ... More
Agonist-specific behaviour of the intracellular Ca2+ response in rat hepatocytes.
AuthorsChatton JY, Cao Y, Stucki JW
JournalBiochem J
PubMed ID9371717
'A variety of agonists stimulate in hepatocytes a response that takes the shape of repetitive cytosolic free Ca2+ transients called Ca2+ oscillations. The shape of spikes and the pattern of oscillations in a given cell differ depending on the agonist of the phosphoinositide pathway that is applied. In this study, ... More
A noninvasive fluorimetric procedure for measurement of membrane potential. Quantification of the NADPH oxidase-induced depolarization in activated neutrophils.
AuthorsJankowski A, Grinstein S
JournalJ Biol Chem
PubMed ID10473559
'The electrogenic activity of the NADPH oxidase is associated with depolarization of the plasma membrane in activated neutrophils. The magnitude and consequences of this depolarization, however, remain unknown. Neutrophils are not amenable to electrophysiological determinations of membrane potential by current clamp. Instead, the occurrence of depolarization has been inferred from ... More
Tumor necrosis factor-alpha autoregulates interleukin-6 synthesis via activation of protein kinase C. Function of sphingosine 1-phosphate and phosphatidylcholine-specific phospholipase C.
AuthorsKozawa O, Suzuki A, Kaida T, Tokuda H, Uematsu T
JournalJ Biol Chem
PubMed ID9312119
'We investigated the mechanism of interleukin-6 (IL-6) synthesis induced by tumor necrosis factor-alpha (TNF) in osteoblast-like MC3T3-E1 cells. TNF stimulated the synthesis of IL-6 dose dependently in the range between 1 and 30 ng/ml. Staurosporine and calphostin C, inhibitors of protein kinase C (PKC), significantly enhanced the TNF-induced synthesis of ... More
Effects of MeCh, thapsigargin, and La3+ on plasmalemmal and intracellular Ca2+ transport in lacrimal acinar cells.
AuthorsKwan CY, Takemura H, Obie JF, Thastrup O, Putney JW
JournalAm J Physiol
PubMed ID2360617
'The Ca2(+)-mobilizing actions of the muscarinic receptor agonist, methacholine (MeCh), and the microsomal Ca2+ pump inhibitor, thapsigargin, were investigated in lacrimal acinar cells. As previously shown for parotid cells (J. Biol. Chem. 264: 12266-12271, 1989), thapsigargin activates both internal Ca2+ release and Ca2+ entry from the extracellular space without increasing ... More
Calcium is a key signaling molecule in beta-lapachone-mediated cell death.
AuthorsTagliarino C, Pink JJ, Dubyak GR, Nieminen AL, Boothman DA
JournalJ Biol Chem
PubMed ID11279125
'beta-Lapachone (beta-Lap) triggers apoptosis in a number of human breast and prostate cancer cell lines through a unique apoptotic pathway that is dependent upon NQO1, a two-electron reductase. Downstream signaling pathway(s) that initiate apoptosis following treatment with beta-Lap have not been elucidated. Since calpain activation was suspected in beta-Lap-mediated apoptosis, ... More
Evidence for reduced capacity for Ca2+ removal from the cytosol in submandibular cells of newborn rats.
AuthorsZhang GH, Wells J, Willis S, Martinez JR
JournalBiochem Biophys Res Commun
PubMed ID8912654
'The increase in cytosolic free Ca2+ concentration ([Ca2+]i) seen in submandibular cells of early postnatal rats following exposure to acetylcholine (ACh) is larger than in cells of adult rats. To elucidate possible reasons for this difference, we compared Ca2+ movements through Ca2+ pumps in both types of cells using Ca(2+)-sensitive ... More
Endoplasmic reticulum Ca2+ depletion unmasks a caffeine-induced Ca2+ influx in human aortic endothelial cells.
AuthorsCorda S, Spurgeon HA, Lakatta EG, Capogrossi MC, Ziegelstein RC
JournalCirc Res
PubMed ID7554146
'Intracellular Ca2+ pools contribute to changes in cytosolic [Ca2+] ([Ca2+]i), which play an important role in endothelial cell signaling. Recently, endothelial ryanodine-sensitive Ca2+ stores were shown to regulate agonist-sensitive intracellular Ca2+ pools. Since caffeine binds the ryanodine Ca2+ release channel on the endoplasmic reticulum in a variety of cell types, ... More
Potentiation of Fcepsilon receptor I-activated Ca(2+) current (I(CRAC)) by cholera toxin: possible mediation by ADP ribosylation factor.
AuthorsMcCloskey MA, Zhang L
JournalJ Cell Biol
PubMed ID10629224
'Antigen-evoked influx of extracellular Ca(2+) into mast cells may occur via store-operated Ca(2+) channels called calcium release-activated calcium (CRAC) channels. In mast cells of the rat basophilic leukemia cell line (RBL-2H3), cholera toxin (CT) potentiates antigen-driven uptake of (45)Ca(2+) through cAMP-independent means. Here, we have used perforated patch clamp recording ... More
Induction of maturation-promoting factor during Xenopus oocyte maturation uncouples Ca(2+) store depletion from store-operated Ca(2+) entry.
AuthorsMachaca K, Haun S
JournalJ Cell Biol
PubMed ID11781335
'During oocyte maturation, eggs acquire the ability to generate specialized Ca(2+) signals in response to sperm entry. Such Ca(2+) signals are crucial for egg activation and the initiation of embryonic development. We examined the regulation during Xenopus oocyte maturation of store-operated Ca(2+) entry (SOCE), an important Ca(2+) influx pathway in ... More
Thapsigargin-induced degranulation of mast cells is dependent on transient activation of phosphatidylinositol-3 kinase.
AuthorsHuber M, Hughes MR, Krystal G
JournalJ Immunol
PubMed ID10861044
'Thapsigargin, which elevates cytosolic calcium levels by inhibiting the sarcoplasmic/endoplasmic reticulum calcium-dependent ATPase, was tested for its ability to degranulate bone marrow-derived mast cells (BMMCs) from src homology 2-containing inositol phosphatase +/+ (SHIP+/+) and SHIP-/- mice. As was found previously with steel factor, thapsigargin stimulated far more degranulation in SHIP-/- ... More
Meiosis reinitiation in Ruditapes philippinarum (Mollusca): involvement of L-calcium channels in the release of metaphase I block.
AuthorsMoreau M, Leclerc C, Guerrier P
JournalZygote
PubMed ID8913029
'Prophase-arrested oocytes of Ruditapes philippinarum cannot be fertilised or stimulated by excess KCl, in contrast to the situation found in other bivalve species such as Barnea and Spisula. However, these oocytes can be triggered to reinitiate meiosis following treatment by serotonin or several pharmacological agents (calcium ionophores, thapsigargin, weak bases) ... More