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PubMed1991

Induction of T cell CD7 gene transcription by nonmitogenic ionomycin-induced transmembrane calcium flux.

The CD7 molecule is a 40-kDa member of the Ig superfamily that has structural homology to the murine Thy-1 molecule and is acquired early in human T cell ontogeny. Previous studies have demonstrated that expression of the CD7 molecule is markedly up-regulated during T cell activation. In this study, we have studied the signals required for CD7 up-regulation on human T cells. We found that nonmitogenic amounts of ionomycin selectively and maximally up-regulated T cell CD7 on mature (peripheral blood) T cells after 24 h. Whereas CD7 expression was increased 78 +/- 25% by 0.5 microM ionomycin, expression of CD25 (IL-2R alpha), class II MHC, 4F2, transferrin receptor, CD2, CD3, CD4, CD5, and CD8 molecules was not increased. Ionomycin-induced CD7 surface expression was associated with peak increases in CD7 mRNA after 4 to 6 h. Transcriptional analysis and CD7 mRNA half-life determination revealed the increase in CD7 mRNA was the result of increased CD7 gene transcription 1 h after ionomycin stimulation and was not due to prolongation of CD7 mRNA half-life. The up-regulation of surface CD7 expression by ionomycin was dependent on extracellular calcium and did not require the activation of T cell tyrosine protein kinase. Mitogenic CD2 and CD3 mAb as well as stimulation of T cells by PHA also up-regulated CD7 expression. CD7 up-regulation by ionomycin was transient (24 to 72 h) and inhibitable by cyclosporin A, whereas CD7 up-regulation by PHA was sustained over 5 to 7 days and was significantly less inhibitable by cyclosporin A. These data demonstrate that induction of a transmembrane calcium flux generates signals that lead to CD7 gene transcription.

Antibodies, Monoclonal↗
PubMedDate not supplied

The role of external and internal free Ca2+ concentration on ionomycin induced leukotriene C4 formation in rat basophilic leukemia cells.

Rat basophilic leukemia (RBL-2H3) cells serve as a model to examine the role of external and internal free Ca2+ concentration [Ca2+]i, following ionomycin induced stimulation of leukotriene C4 (LTC4) formation. Brief exposure of RBL cells to Ca(2+)-free medium abolished the effect of ionomycin on elevation of [Ca2+]i (monitored by Quin-2/AM) and on stimulation of LTC4 production. In Ca(2+)-rich medium (1.8 mM) however there was a large increase in both parameters. We showed recently (Her et al., 1990) that hydrocortisone (HC) and dexamethasone markedly suppressed the elevated [Ca2+]i induced by antigen. Following HC pretreatment, there was a modest (35%) suppression of [Ca2+]i elevation induced by submaximal (0.1 microM) as well as maximal (1 microM) doses of ionomycin (nevertheless, 8 fold increase above basal level was still observed), LTC4 formation, however, was only inhibited (47%) by HC when induced by submaximal dose of ionomycin, but not that induced by higher doses of ionomycin. Phorbol ester (TPA) abolished elevation of [Ca2+]i induced by antigen. Short treatment with TPA had a modest inhibitory (28%) effect on elevation of [Ca2+]i and on LTC4 formation (23%) induced by ionomycin. It is proposed that high [Ca2+]i, possibly originated mainly from extracellular source, is essential for induction of LTC4 formation.

Animals↗
PubMed1987

Ionomycin inhibits thyrotropin-releasing hormone-induced translocation of protein kinase C in GH4C1 pituitary cells.

Thyrotropin-releasing hormone (TRH) induces rapid and transient conversion of protein kinase C (Ca2+/phospholipid-dependent enzyme) from a soluble to a particulate-bound form in GH4C1 rat pituitary cells. Ionomycin (200 nM), a calcium ionophore, had no effect by itself on the subcellular distribution of protein kinase C. However, pretreatment of the cells with 200 nM ionomycin inhibited by greater than 50% the ability of TRH to cause translocation of protein kinase C from the cytosol to the particulate cell fraction. Inhibition by ionomycin required that the cells be incubated with the ionophore for at least 10 s before TRH addition. Ionomycin pretreatment did not alter the kinetics of TRH-induced protein kinase C redistribution. Incubation of the cells with 43 mM potassium prior to TRH addition almost completely reversed the inhibition induced by ionomycin. We propose that the mechanism by which ionomycin attenuates TRH action on protein kinase C may involve the capacity of the ionophore to empty the intracellular calcium reservoir which normally releases calcium into the cytosol in response to TRH. Our result provides evidence that the rise in intracellular calcium, which accompanies diacylglycerol formation following TRH action on polyphosphatidylinositide hydrolysis, may be required to achieve maximal conversion of protein kinase C to its presumed active, membrane-bound form in these cells.

Animals↗
PubMed1989

The calcium ionophore ionomycin can prime, but not activate, the reactive oxygen generating system in differentiated HL-60 cells.

Both the chemotactic peptide formylmethionyl-leucyl-phenylalanine (FMLP) and the calcium ionophore ionomycin induced a metabolic response in normal neutrophils. However, the presence of azide, a potent inhibitor of the hydrogen peroxide-consuming enzymes catalase and myeloperoxidase, was required to detect any release of hydrogen peroxide induced by ionomycin. In differentiated HL-60 cells, only FMLP stimulation was associated with any notable metabolic activation. The response to FMLP proceeds with a rate and time course similar to that seen in normal cells. The use of ionomycin as a stimulating agent did not result in any detectable activation of the system that generates reactive oxygen metabolites, even if azide was present in the measuring system. Raising the concentration of cytoplasmic free Ca2+ is therefore not sufficient to activate the system responsible for the generation of reactive oxygen metabolites in HL-60 cells. However, preincubation with ionomycin primed HL-60 cells to an increased response during stimulation with the chemotactic peptide FMLP and the phorbol ester PMA. Since HL-60 cells lack specific granules but have an intact ligand-receptor coupling mechanism, a role for the subcellular granule is proposed, in the generation of reactive oxygen species in normal granulocytes, and analysis of the data presented leads to two conclusions: 1) FMLP, which acts through cells surface receptors, causes the cells to produce oxygen radicals, which to a large extent are released from the cells, a process that is not dependent on the specific granule content of the cells, whereas 2) ionomycin, which bypasses cell-surface receptors, is also capable of stimulating an oxygen-radical formation that is granule dependent and retained inside the cells. Furthermore, the results suggest that an increase in intracellular Ca2+ is not sufficient to initiate activation of the plasma membrane-bound system that generates reactive oxygen metabolites, but the results support a role for Ca2+ in the priming event.

Adult↗
PubMed1989

Reversibility of the ionomycin promoted synaptosomal hydrogen peroxide production.

We previously reported on the release of hydrogen peroxide from guinea pig cerebral cortex synaptosomes (13). An important finding was that in glutathione depleted synaptosomes a linear release of hydrogen peroxide is rapidly induced on addition of the Ca++ -ionophore ionomycin (in the presence of Ca++) or upon depolarization of the plasma membrane. We report here that the ionomycin induced hydrogen peroxide is reversed following the addition of bovine serum albumin which strongly binds the ionophore, to be reactivated by further addition of excess ionomycin, or of the depolarizing agent KC1. Similarly, the effect of ionomycin is removed on decreasing the concentration of free Ca++. Bovine serum albumin, which counteracts the effect of ionomycin on the release of H2O2, also counteracts the effect of the ionophore on the movements of Ca++ and the release of gamma-aminobutyrate. These findings support the idea that the synaptosomal production of H2O2 is a carefully controlled important physiological event.

Animals↗
PubMed1988

Partial restoration of Con A-induced proliferation, IL-2 receptor expression, and IL-2 synthesis in aged murine lymphocytes by phorbol myristate acetate and ionomycin.

The activation by concanavalin A (Con A) of murine lymphocytes derived from aged animals is impaired, as demonstrated by lower IL-2 synthesis, display of fewer IL-2 receptors, and less [3H]thymidine incorporation relative to similarly treated cells from young animals. The ability of the phorbol ester, phorbol 12-myristate 13-acetate (PMA), and the calcium ionophore, ionomycin, in conjunction with Con A, to improve these parameters of activation has been assessed. When splenic lymphocytes derived from aged mice are cultured with Con A plus ionomycin, IL-2 synthesis and IL-2 receptor expression are increased over the values obtained in parallel cultures triggered by Con A alone up to levels equal to that obtained in Con A-activated young cultures. The proliferative response is less sensitive to the augmenting effect of ionomycin. PMA is much less effective in improving these parameters of Con A activation. PMA plus ionomycin, in the absence of Con A, triggers cell cycle transition of lymphocytes derived from both aged and young animals. Both IL-2 synthesis and IL-2 receptor expression induced by PMA plus ionomycin reach levels equal or near equal that found in parallel cultures of cells from young animals; however, proliferation is lower than in young adult cultures.

Animals↗
PubMed1990

Molecular signals in B cell activation. I. Differential refractory effects of incomplete signaling by ionomycin or PMA relate to autocrine IL-2 production and IL-2R expression.

The molecular signals required by resting (G0) B cells for the induction of cell cycle entry, IL-2 production, and high-affinity IL-2 receptor (IL-2R) expression were defined and the effects of incomplete activation signals on the subsequent response to complete signals were examined. Highly enriched rabbit peripheral blood B cells were activated with a calcium ionophore, ionomycin, and a protein kinase C (PKC) activating phorbol ester, phorbol myristate acetate (PMA). It was observed that cell cycle entry to early G1 was induced by either reagent acting alone, but both reagents were required to stimulate IL-2 production, IL-2R expression, and DNA synthesis. These effects of ionomycin and PMA were shown to be mediated by increased intracellular calcium ion concentration [Ca2+]i and PKC activation, respectively. Although, increased [Ca2+]i or PKC activation each led to cell cycle entry, the subsequent response of these preactivated cells to complete activation with both signals was different: Cells pretreated with PMA alone for up to 24 hr could progress further to DNA synthesis after the addition of ionomycin. In contrast, cells activated with ionomycin alone, or those cultured without any stimulus, progressively lost the ability to show DNA synthesis after complete activation. The failure to progress to DNA synthesis in these two cases was, however, differentially regulated by the ability of these cells to produce IL-2 and to express IL-2R. Ionomycin-pretreated cells retained the ability to produce IL-2 but showed about 70% reduction in the numbers of IL-2R; whereas cells cultured without any stimulus lost the ability to produce IL-2 after subsequent complete activation, but showed lesser reduction in IL-2R expression.

Animals↗
PubMed1995

Involvement of CD5 in Th1 and Th2 contact-mediated rescue of anti-mu and ionomycin induced growth inhibition in a B cell lymphoma.

Cross-linking of membrane Ig receptors by anti-mu antibodies (Ab) or treatment with ionomycin induced complete growth arrest and subsequent apoptotic cell death in an immature B cell lymphoma, BKS-2. The growth-inhibitory signals delivered by anti-mu and ionomycin were overcome by anti-CD3-activated Th2 clones D10.G4 and F1 and by Th1 cell clone S53. In this report the Th-mediated growth reversal in BKS-2 cells was shown to require contact-dependent interactions when the inhibition was caused by immobilized anti-mu or ionomycin. Th2 cells in transwells (lymphokines) failed to protect BKS-2 cells from the growth-inhibitory effect of immobilized anti-mu or ionomycin. Monoclonal antibodies to CD5 or CD40 ligands on activated Th cells partially inhibited the Th2 contact-dependent growth reversal of BKS-2 cells whereas simultaneous addition of both antibodies effectively prevented the delivery of contact-mediated growth signal. In contrast, anti-class I or class II Ab did not affect Th cell mediated growth reversal of BKS-2 cells. These data demonstrated that noncognate physical interaction with Th cells was essential for the recovery of BKS-2 cells when the latter were growth-arrested by strong inhibitory stimuli such as immobilized anti-mu and ionomycin. Further CD5 as well as CD40 ligands on Th cells are important for signal transduction in this type of T-B interaction.

Animals↗
PubMed1990

Activation of human T lymphocytes by phorbol-12,13-dibutyrate and ionomycin.

The calcium ionophore ionomycin and the phorbol ester phorbol-12,13-dibutyrate (PDBu) are shown to have a synergistic effect upon interleukin 2 (IL-2) production, interleukin 2 receptor expression, and T-lymphocyte proliferation. The proliferative response was inhibited by addition of a monoclonal antibody directed against the IL-2R (Tac antigen) demonstrating that PDBu and ionomycin induce T-cell growth through an IL-2-dependent autocrine pathway. Sequential stimulation with PDBu and ionomycin failed to induce IL-2 production, IL-2R expression, and consequently proliferation of the T cells, indicating that T-cell activation requires simultaneous activation of protein kinase C (PKC) and elevation of cytosolic calcium. Exposure of T cells to both agents for different times resulted in IL-2 production, IL-2R expression, and proliferation in proportion to the duration of incubation with at least 4 h required for maximal T-cell activation. Further, in the presence of PDBu maximal T-cell activation was found to require stimulation with ionomycin for 4 h, indicating that a sustained increase in free cytoplasmic calcium of several hours' duration is essential for T-cell activation. In contrast T cells incubated with ionomycin were induced to produce IL-2 and express IL-2Rs upon brief exposure to PDBu with a 2-h incubation period being sufficient for maximal T-cell activation. Thus transient activation of PKC seems to be sufficient for activation of the IL-2 gene and IL-2R gene. However, maximal T-cell activation requires activation of PKC for at least 2 h.

Antibodies, Monoclonal↗
PubMed1993

Ionomycin-induced acetylcholine release and its inhibition by adenosine at frog motor nerve endings.

1. Acetylcholine (ACh) evoked secretion by the calcium ionophore, ionomycin, was studied at frog motor nerve endings. 2. Bath application of ionomycin stimulated an irreversible increase in the rate of spontaneous, quantal ACh release in the presence of extracellular Ca2+. In contrast, local application of ionomycin stimulated a rapid, reversible acceleration of spontaneous ACh release. 3. The magnitude of the secretory response to ionomycin was dependent both upon the concentration of ionophore and the concentration of extracellular Ca2+. 4. Adenosine or 2-chloroadenosine inhibited ionomycin-stimulated ACh release with the same potency and efficacy observed previously for these adenosine analogues as inhibitors of ACh secretion evoked by nerve impulses. 5. These results support the conclusion that adenosine receptor activation inhibits quantal ACh secretion at a site distal to that of Ca2+ entry at frog motor nerve endings.

2-Chloroadenosine↗
PubMed1997

Mechanisms of ionomycin-induced endothelial cell barrier dysfunction.

Myosin light chain (MLC) phosphorylation catalyzed by the Ca(2+)- calmodulin-dependent MLC kinase (MLCK) is critical to thrombin-mediated endothelial cell gap formation and barrier dysfunction. We have tested the hypothesis that the Ca2+ ionophore ionomycin stimulates MLCK-dependent endothelial cell contraction and permeability. Ionomycin significantly increased albumin clearance and decreased electrical resistance across confluent bovine pulmonary microvascular and macrovascular endothelial cell monolayers in a concentration-dependent manner that was temporally similar to that produced by thrombin. In contrast, however, ionomycin produced a significant Ca(2+)-dependent reduction in the levels of phosphorylated MLC with evidence of serine/threonine phosphatase activation. Potential MLCK-independent mechanisms of endothelial cell permeability were examined with little evidence to support a role for stimulated nitric oxide synthase or phospholipase A2 activities. Importantly, ionomycin produced 1) reductions in the activities of the barrier protective adenylate cyclase and the adenosine 3',5'-cyclic monophosphate-dependent protein kinase A, 2) dramatic dose- and time-dependent inhibition of endothelial cell tyrosine kinase activities, and 3) marked decreases in the phosphotyrosine content of the p125 focal adhesion kinase. These data indicate that ionomycin produces endothelial cell barrier dysfunction by mechanisms that are independent of MLCK activation and may involve reductions in endothelial cell tethering forces via inhibition of protein kinase A and tyrosine kinase activities, especially the p125 focal adhesion kinase.

Adenylyl Cyclases↗
PubMed1998

Two distinct effects of 12S-hydroxyeicosatetraenoic acid on platelet aggregation by zooxanthellatoxin-A and ionomycin.

The marine toxin zooxanthellatoxin-A (ZT-A) and the Ca2+ ionophore ionomycin caused aggregation in rabbit platelets. While ZT-A-induced platelet aggregation was inhibited by indomethacin, ionomycin-induced aggregation was potentiated by the drug. In contrast, both ZT-A- and ionomycin-induced accumulations of thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2), were completely inhibited by indomethacin. 12S-Hydroxyeicosatetraenoic acid (12-HETE), which could be accumulated in the presence of indomethacin, inhibited ZT-A-induced aggregation, but it potentiated the ionomycin-induced one. These results suggest that the different effects of indomethacin may be attributed to the distinct effects of 12-HETE on ZT-A- and ionomycin-induced platelet aggregations.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

Stimulation of phospholipase D by phorbol esters and ionomycin in bovine corneal epithelial cells.

This study was performed to determine the effects of phorbol esters and ionomycin on phospholipase D (PLD) activity in bovine corneal epithelial cells (BCEC). The cells were prelabeled with [3H]myristic acid and incubated for specific time intervals with various test agents in the presence and absence of ethanol. The PLD activity was assayed by monitoring the formation of labeled phosphatidylethanol ([3H]PEt) in [3H]myristate labeled cells. In the absence of ethanol, 1 microM phorbol 12-myristate 13-acetate (PMA) increased the formation of labeled phosphatidic acid ([3H]PA) with no significant effect on the radioactivity of [3H]PEt. In the presence of 85 mM ethanol, whereas there was only a small further increase in [3H]PA, the formation of [3H]PEt was increased by several-fold, demonstrating activation of PLD by the phorbol ester. The effects of PMA were time- and dose-dependent, and were mimicked by phorbol 12,13-dibutyrate. The inactive phorbol derivatives, 4-alpha-phorbol, 4-alpha-phorbol 12,13-didecanoate, 4-alpha-phorbol 12-myristate 13-acetate and 4-alpha-phorbol 12,13-dibutyrate, were without effect. Short-time (30 min) incubation of BCEC with staurosporine or H-7, or prolonged (20 hours) incubation with PMA rendered the cells less sensitive to subsequent treatment with PMA, suggesting that activation of PLD in the cells is mediated by protein kinase C (PKC). Addition of 20 microM ionomycin in the presence of ethanol also increased the formation of [3H]PA and [3H]PEt in a time- and dose-dependent manner. Co-presence of ionomycin and PMA at submaximal concentrations in the incubation medium resulted in increased formation of [3H]PA and [3H]PEt which was less than their individual effects combined, indicating a lack of synergism between Ca2+ and PMA in activating PLD. Incubation of BCEC with staurosporine resulted in significant inhibition of ionomycin-induced production of [3H]PEt, suggesting that in addition to direct activation of PLD by Ca2+, the enzyme is probably stimulated by sequential activation of PLC (producing diacylglycerol) and PKC following the ionomycin addition. We conclude that BCEC possess PLD which is stimulated by PKC as well as elevated intracellular Ca2+.

Animals↗
PubMed1995

cAMP-independent effects of cholera toxin on B cell activation. III. Cholera toxin A subunit-mediated ADP-ribosylation acts synergistically with ionomycin or IL-4 to induce B cell proliferation.

To investigate whether ADP-ribosylation of proteins by cholera toxin could influence B cell activation, B cells were incubated with the A subunit of cholera toxin. Ionomycin acted synergistically to induce B cell proliferation with the A subunit of cholera toxin but not with cAMP-enhancing agents or with the B subunit of cholera toxin, suggesting that the synergistic effect of the A subunit was mediated via ADP-ribosylation and not via cAMP elevations or ganglioside GM1 binding. Indeed, inhibitors of ADP-ribosylation blocked the synergistic effect. Unlike anti-Ig, B cell proliferation stimulated by LPS or by the combination of the A subunit and ionomycin was observed in protein kinase C (PKC)-depleted B cells. However, neither the A subunit nor ionomycin enhanced B cell proliferation stimulated by low dose LPS, suggesting that the A subunit plus ionomycin stimulated an activation pathway distinct from the LPS-stimulated pathway. Additionally, unlike LPS, the A subunit plus ionomycin did not stimulate B cells in vitro to secrete Ig. IL-4 acted synergistically with the A subunit to induce B cell proliferation to the same extent as it did with anti-Ig; unlike the anti-Ig plus IL-4 synergy, however, the A subunit plus IL-4-mediated synergy persisted in PKC-depleted B cells. Taken together, our data suggest that cholera toxin A subunit-catalyzed ADP-ribosylation modifies a non-Gs protein involved in the activation of B cells, either through a novel pathway or at a point distal to the activation of PKC along the anti-Ig-stimulated pathway.

Adenosine Diphosphate Ribose↗
PubMed1992

Importance of bicarbonate ion for intracellular pH regulation in antigen- and ionomycin-stimulated RBL-2H3 mast cells.

In RBL-2H3 rat basophilic leukemia cells, Ca2+ influx and secretion are activated by antigens that crosslink IgE-receptor complexes and by the Ca2+ ionophore, ionomycin. Here we report that antigen-stimulated Ca2+ influx and secretion are impaired and ionomycin-induced responses are strongly inhibited following the removal of HCO3- from the medium. These results raised the possibility that HCO3(-)-dependent pH regulation mechanisms play a role in the cascade of events leading to mast cell activation. To test this hypothesis, intracellular pH (pHi) was measured by ratio imaging microscopy in individual RBL-2H3 cells labeled with 2',7'-bis-(2-carboxyethyl)-5-(6) carboxyfluorescein (BCECF). In unstimulated cells, it was found that basal pHi in the presence of HCO3- is 7.26, significantly greater than pHi in its absence, 7.09 (P less than 10(-6]. These results, as well as evidence that pHi increases rapidly when HCO3- is added to cells initially incubated in HCO3(-)-free medium, indicate that unstimulated cells use a HCO3(-)-dependent mechanism to maintain cytoplasmic pH. Further analyses comparing unstimulated with stimulated cells showed that antigen causes a small transient acidification in medium containing HCO3- and a larger sustained acidification in HCO3(-)-depleted medium. Ionomycin is a more potent acidifying agent, stimulating a sustained acidification in complete medium and causing further acidification in HCO3(-)-free medium. These results support the hypothesis that the inhibition of antigen- and ionomycin-induced 45Ca2+ influx and secretion in cells incubated in HCO3(-)-free medium is at least partially due to the inactivation of HCO3(-)-dependent mechanisms required to maintain pH in unstimulated cells and to permit pH recovery from stimulus-induced acidification.

Animals↗
PubMed1984

Characterization of the response of human thymocytes and blood lymphocytes to the synergistic mitogenicity of 12-O-tetradecanoylphorbol-13-acetate (TPA)-ionomycin.

The combination of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore ionomycin is synergistically mitogenic for human fetal and infant thymocytes as well as peripheral blood lymphocytes. Optimal mitogenic stimulation is achieved when TPA and ionomycin are used at doses of 0.5-1 ng/ml and 0.5-1 microgram/ml, respectively. Phenotypic analysis and cell sorting show that the thymocytes responsive to the mitogen have a mature or medullary phenotype (T1+, T3+, T11+, T6-, HLA-A,B++, [TdT]-); similarly in blood the T cell subsets (T11+, T4+ and T11+, T8+) are selectively responsive to TPA-ionomycin. Both activated lymphocytes and thymocytes express HLA-DR antigens as well as activation antigens such as T9, T10 and T cell activation antigen. T cells activated by TPA-ionomycin can be grown for periods of up to 50 days without addition of exogeneous interleukin 2. The observations may have implications for the membrane-associated signals involved in T cell growth and proliferation.

Cell Division↗
PubMed2002

Activation of stress response by ionomycin in rat hepatoma cells.

All living systems respond to a variety of stress conditions by inducing the synthesis of stress or heat shock proteins (HSPs), which transiently protect cells. HSP synthesis was preceded by an increase in intracellular free calcium concentration [(Ca(2+))i]. In this study, we show that Ca(2+) ionophore, ionomycin, induced an immediate increase in intracellular free Ca(2+) and examined how this increase affects heat shock response in rat hepatoma cell line H4II-E-C3. Results indicate that incubating H4II-E-C3 cells with 0.3 microM ionomycin at 37 degrees C for 15 min results in the induction of HSP 70 in both Ca(2+)-containing and Ca(2+)-free medium. Associated with this increase in free Ca(2+) is an in vivo change in membrane organization and activation of signaling molecules like ERKS and SAPKs/JNK. In Ca(2+) containing medium HSP 70 induction mediated by HSF-HSE interaction was faster upon ionomycin treatment as compared to heat shock. Our results show that ionomycin, at sub lethal concentration, increases intracellular free Ca(2+) concentration, activates SAPK/JNK and HSF-HSE interaction, and induces HSP 70 synthesis.

Animals↗
PubMed1996

Effect of ionomycin on cell pH in isolated renal proximal tubules.

In isolated rabbit proximal tubules the addition of 2.0 microM but not 0.2 microM ionomycin induced a sustained increase in cell pH ([pH]i). This [pH]i response to 2.0 microM ionomycin was shown to be independent of several transporters such as Na+/H+ exchanger, Na(+)-HCO3- cotransporter, Cl-/HCO3- exchanger, or H(+)-ATPase. On the other hand, the removal of extracellular Ca2+ abolished the [pH]i increase or even induced a transient [pH]i decrease in the presence of ionomycin. These results are consistent with the induction of Ca2+/H+ exchange by ionomycin. Therefore Ca2+ ionophores should be used with caution as probes to estimate renal tubule functions.

Animals↗