Increased intracellular Ca2+ induces Ca2+ influx in human T lymphocytes.

Haverstick, Doris M.; Gray, Lloyd S.

doi:10.1091/mbc.4.2.173

Cited by 34 publications

(18 citation statements)

References 36 publications

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“…The effects of calcium reuptake inhibitors and chelation on the caffeine/Aß response also indicate that a change in [Ca2~j 1 is the responsible factor. Calcium release in some cells also can trigger calcium influx, either through L-channel activation (see below), a "capacitative entry" effect from store depletion, or a "feedforward" mechanism (Haverstick and Gray, 1993). We have not addressed the degree to which influx from any of these mechanisms contributes to caffeinestimulated Aß production.…”

Section: Discussionmentioning

confidence: 99%

Caffeine Stimulates Amyloid β‐Peptide Release from β‐Amyloid Precursor Protein‐Transfected HEK293 Cells

Querfurth

Jiang²,

Geiger

et al. 1997

Journal of Neurochemistry

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Extracellular amyloid ß-peptide (Aß) deposition is a pathological feature of Alzheimer's disease and the aging brain. Intracellular Aß accumulation is observed in the human muscle disease, inclusion body myositis. Aß has been reported to be toxic to neurons through disruption of normal calcium homeostasis. The pathogenic role of Aß in inclusion body myositis is not as clear. Elevation of intracellular calcium following application of calcium ionophore increases the generation of Aß from its precursor protein (ßAPP). A receptor-based mechanism for the increase in Aß production has not been reported to our knowledge. Here, we use caffeine to stimulate ryanodine receptor (RYR)-regulated intracellular calcium release channels and show that internal calcium stores also participate in the genesis of Aß. In cultured HEK293 cells transfected with ßAPP cDNA, caffeine (5-10 mM) significantly increased the release of Aß fourfold compared with control. These actions of caffeine were saturable, modulated by ryanodine, and inhibited by the RYR antagonists ruthenium red and procaine. The calcium reuptake inhibitors thapsigargin and cyclopiazonic acid potentiated caffeine-stimulated Aß release. NH 4CI and monensin, agents that alter acidic gradients in intracellular vesicles, abolished both the caffeine and ionophore effects. Immunocytochemical studies showed some correspondence between the distribution patterns of RYR and cellular ßAPP immunoreactivities. The relevance of these findings to Alzheimer's disease and inclusion body myositis is discussed. Key Words: CaffeineAmyloid ß-peptide-ß-Amyloid precursor protein-HEK293 cells-Alzheimer's disease-Inclusion body myositis. J. Neurochem. 69, 1580-1591 (1997).ß-Amyloid-laden plaques and vascular deposits are pathologic hallmarks common to Alzheimer' s disease (AD) and the normal aging process. The 4-kDa amybid ß-peptide (Aß) is a secreted 39-42 amino acid peptide by-product of endocytotic and secretory processes (involving unidentified proteases referred to as ß-and y-secretases) acting on the ß-amyloid precursor protein (ßAPP) . The predominant proteolytic event of ßAPP processing leads to the secretion of a large NH2-terminal ectodomain (ßPP5) (Weidemann et al., 1989;Esch et al., 1990;Sisodia et al., 1990) and retention of a 10-kDa COOHterminal membrane fragment (Selkoe et al., 1988) that is catalyzed by an unknown protease termed a-secretase. The latter scission occurs at Aß position 16, thereby precluding formation of intact Aß (Esch et al., 1990;Oltersdorf et al., 1990), and occurs either at the cell surface or within secretory vesicles targeted for exocytosis (Sisodia et al., 1990;Sambamurti et al., 1992;De Strooper et al., 1993; Haass et al., 1995b). A second trafficking pathway involves the reinternalization of cell surface ßAPP by endosomes that are ultimately targeted to lysosomes (Yamazaki et al., 1995). Constitutive production of Aß from wild-type ßAPP molecules occurs mainly via endocytosis of cell surface-associated ßAPP (Koo and Squazzo, 1994).Aß deposits ...

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Section: Discussionmentioning

confidence: 99%

Caffeine Stimulates Amyloid β‐Peptide Release from β‐Amyloid Precursor Protein‐Transfected HEK293 Cells

Querfurth

Jiang²,

Geiger

et al. 1997

Journal of Neurochemistry

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“…Secondary antibodies, 1.5 g of F(abЈ) 2 fragment of rabbit anti-mouse IgM per ml (for BCR cross-linking alone) or 3 g of intact rabbit anti-mouse IgM per ml (for BCR plus FcR cross-linking), were added prior to measurement. Using an SLM 8100-C spectrofluorimeter (22), calcium flux was recorded upon excitation at 340 nm as the ratio of fluorescence emissions at 398 and 480 nm. The background was recorded for 20 s, followed by addition of mouse anti-chicken IgM (M4) antibody at 1 g/ml.…”

Section: Methodsmentioning

confidence: 99%

Essential Role for the C-Terminal Noncatalytic Region of SHIP in FcγRIIB1-Mediated Inhibitory Signaling

Aman

Walk

March

et al. 2000

Molecular and Cellular Biology

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B-cell immune response to antigens is terminated or attenuated by surface receptors such as Fc␥RIIB1 and CD22 on B cells (5,11,34,48). These inhibitory receptors recruit specific intracellular signaling proteins, which play a key role in attenuating the early activation events initiated by cross-linking of the B-cell receptor (BCR). Fc␥RIIB1 is an important mediator of the attenuation of B-cell activation by antibody-antigen immune complexes in the later phases of the immune response (49). Coengagement of Fc␥RIIB1 with BCR results in a potent inhibitory signal that depends on the recruitment of Src homology 2-containing inositol phosphatase (SHIP). SHIP binds to the phosphorylated immunotyrosine-based motif (ITIM) in the cytoplasmic region of Fc␥RIIB1 (43, 44), and SHIP-mediated dephosphorylation of specific phosphoinositide products has been implicated in terminating the BCR-induced activation events (4, 14, 53).SHIP was initially characterized in hematopoietic cells as a 145-kDa phosphoprotein that coprecipitated with the adapter protein Shc upon stimulation of specific receptors (6-8, 37, 50, 52, 54). Molecular cloning of SHIP identified it as a 5Ј-inositolphosphatase (5Ј-IPase), based on homology with other 5Ј-IPases (9,13,29,36,45,57). SHIP specifically dephosphorylates phosphatidylinositol-3,4,5-trisphosphate (PIP3), a major product of phosphoinositide-3-kinase (PI3K) enzymatic action, as well as inositoltetrakisphosphate (IP4), both in vitro (28,36) and in vivo (53). The requirement for SHIP in Fc␥RIIB1-mediated inhibition of BCR signaling has been well established (4,5,14,20,32,44,48,53). Recruitment of enzymatically active SHIP to the receptor complex results in potent inhibition of intracellular calcium flux (12,30,44), diminished activation of the serine-threonine kinase Akt (1, 3, 17, 27), inhibition of the Ras/mitogen-activated protein kinase pathway (56), and the regulation of apoptosis (2, 38, 47). Further evidence for a crucial role for SHIP in negative regulation of BCR signaling comes from studies with SHIP knockout mice as well as SHIP Ϫ/Ϫ Rag Ϫ/Ϫ chimeric mice, in which BCR-mediated responses are heightened and the Fc␥RIIB1-dependent inhibition of BCR responses is abolished (23,39).It is noteworthy that SHIP also negatively regulates histamine release in response to engagement of the immunoglobulin E (IgE) receptor and Steel factor (25,26,43), as well as the proliferative response to interleukin-3 and the macrophage colony-stimulating factor (36). Ex vivo studies with cells from SHIP-deficient mice have suggested that in the absence of SHIP, the myeloid progenitor cells hyperproliferate in response to cytokines and hematopoietic growth factors, with the dose-response curve being left-shifted (23). Taken together, these studies have clearly established a functional role for SHIP as a negative regulator of cytokine and antigen receptor signaling.The 145-kDa isoform of SHIP, the predominant form expressed in hematopoietic cells, is composed of an N-terminal Src homology 2 (SH2) domain, a central...

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“…Cells were washed three times in buffer A (10 mM HEPES, pH 7.4, 3 mM KCl, 1 mM MgCl 2 , 1 mM CaCl 2 , 140 mM NaCl, 0.1% glucose, 1% fetal bovine serum) and suspended at a final concentration of 1 ϫ 10 6 /ml in buffer A. The [Ca 2ϩ ] i was determined from the fluorescence ratio (398/480 nm) with excitation at 360 nm in an SLM 8100 spectrofluorometer (SLM/Aminco, Urbana, IL) in the T format as described previously (4,22). Calibration was conducted as described previously (22,23) using the equation developed for an earlier generation of Ca 2ϩ indicator dyes (24,25).…”

Section: Methodsmentioning

confidence: 99%

“…[Ca 2ϩ ] i -In most electrically nonexcitable cells, the Ca 2ϩ entry pathway can be opened by depletion of the intracellular Ca 2ϩ storage depot (1). In T cells, the Ca 2ϩ entry pathway can be opened in a receptor-dependent or -independent manner, using, respectively, an activating monoclonal antibody to the T cell receptor (OKT3) or thapsigargin (4). The effects of activation of PKC by the phorbol ester PMA on these two methods of opening the Ca 2ϩ entry pathway are shown in Fig.…”

Section: Methodsmentioning

confidence: 99%

“…In T lymphocytes, as well as in most electrically nonexcitable cells, this depletion of the intracellular storage pool induces the opening of the plasma membrane Ca 2ϩ entry pathway and permits influx of extracellular Ca 2ϩ (1). Previously, we have provided evidence that the pathway between release of intracellular Ca 2ϩ and influx of extracellular Ca 2ϩ is mediated by Ca 2ϩ -activated calmodulin (4), which permits Ca 2ϩ entry carried by a current we have called I T (5).…”

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confidence: 99%

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A Role for Protein Kinase CβI in the Regulation of Ca2+ Entry in Jurkat T Cells

Haverstick¹,

Dicus²,

Resnick³

et al. 1997

Journal of Biological Chemistry

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T cell activation leading to cytokine production and cellular proliferation involves a regulated increase and subsequent decrease in the intracellular concentration of Ca 2؉ ([Ca 2؉ ] i ). While much is understood about agonist-induced increases in [Ca 2؉ ] i , less is known about down-regulation of this pathway. Understanding the mechanism of this down-regulation is critical to the prevention of cell death that can be the consequence of a sustained elevation in [Ca 2؉ ] i . Protein kinase C (PKC), activated by the diacylglycerol produced as a consequence of T cell receptor engagement, has long been presumed to be involved in this down-regulation, although the precise mechanism is not wholly clear. In this report we demonstrate that activation of PKC by phorbol esters slightly decreases the rate of Ca 2؉ efflux from the cytosol of Jurkat T cells following stimulation through the T cell receptor or stimulation in a receptorindependent manner by thapsigargin. On the other hand, phorbol ester treatment dramatically reduces the rate of Ca 2؉ influx following stimulation. Phorbol ester treatment is without an effect on Ca 2؉ influx in a different T cell line, HSB. Down-regulation of PKC␤I expression by 18-h phorbol ester treatment is associated with a loss of the response to acute phorbol ester treatment in Jurkat cells, suggesting that PKC␤I may be the isozyme responsible for the effects on Ca 2؉ influx. Electroporation of an anti-PKC␤I antibody, but not antibodies against PKC␣ or PKC␥, led to an increase in the rate of Ca 2؉ influx following stimulation. Taken together, these data suggest that PKC␤I may be a component of the down-regulation of increases in [Ca 2؉ ] i associated with Jurkat T cell activation.Activation of T lymphocytes via stimulation through the T cell receptor for antigen (TCR) 1 leading to proliferation, cytokine production, or effector function requires a regulated increase and subsequent decrease in the intracellular concentration of Ca 2ϩ ([Ca 2ϩ ] i ). The biochemical events associated with activation of T lymphocytes and leading to Ca 2ϩ entry have been extensively studied (1). Engagement of the TCR leads to the activation of phospholipase C, which subsequently cleaves phosphatidylinositol bisphosphate into inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol (DAG). IP 3 , binding to an intracellular receptor, induces the release of Ca 2ϩ from an intracellular storage depot (2). In a receptor-independent manner, the Ca 2ϩ /ATPase inhibitor thapsigargin (3) causes an uncompensated leak of Ca 2ϩ from this internal storage pool. In T lymphocytes, as well as in most electrically nonexcitable cells, this depletion of the intracellular storage pool induces the opening of the plasma membrane Ca 2ϩ entry pathway and permits influx of extracellular Ca 2ϩ (1). Previously, we have provided evidence that the pathway between release of intracellular Ca 2ϩ and influx of extracellular Ca 2ϩ is mediated by Ca 2ϩ -activated calmodulin (4), which permits Ca 2ϩ entry carried by a current we have called I T...

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Increased intracellular Ca2+ induces Ca2+ influx in human T lymphocytes.

Cited by 34 publications

References 36 publications

Caffeine Stimulates Amyloid β‐Peptide Release from β‐Amyloid Precursor Protein‐Transfected HEK293 Cells

Caffeine Stimulates Amyloid β‐Peptide Release from β‐Amyloid Precursor Protein‐Transfected HEK293 Cells

Essential Role for the C-Terminal Noncatalytic Region of SHIP in FcγRIIB1-Mediated Inhibitory Signaling

A Role for Protein Kinase CβI in the Regulation of Ca2+ Entry in Jurkat T Cells

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