Formyl Peptide Receptor Signaling in HL-60 Cells through Sphingosine Kinase

Alemany, Regina; Heringdorf, Dagmar Meyer zu; Koppen, Chris J. van; Jakobs, Karl H.

doi:10.1074/jbc.274.7.3994

Cited by 100 publications

(98 citation statements)

References 33 publications

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“…It therefore appears that the activation of GTP-binding proteins is required in the toxin-activated SM metabolic system. Alemany et al (57) reported that the direct activation of heterotrimeric GTP-binding protein increased production of S1P in HL-60 cells, and sphingosine kinase was activated by GTP␥S. Pertussis toxin inhibited the ␣-toxin-induced hydrolysis of SM in the cell lysates but had no effect on the SMase activity of ␣-toxin, suggesting that ␣-toxin activates endogenous SMase through pertussis toxin-sensitive G i type GTP-binding protein.…”

Section: ␣-Toxin-induced Hemolysis and Sphingomyelin Metabolismmentioning

confidence: 99%

Clostridium perfringens α-Toxin Activates the Sphingomyelin Metabolism System in Sheep Erythrocytes

Ochi

Oda

Matsuda

et al. 2004

Journal of Biological Chemistry

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Clostridium perfringens ␣-toxin induces hemolysis of rabbit erythrocytes through the activation of glycerophospholipid metabolism. Sheep erythrocytes contain large amounts of sphingomyelin (SM) but not phosphatidylcholine. We investigated the relationship between the toxin-induced hemolysis and SM metabolic system in sheep erythrocytes. ␣-Toxin simultaneously induced hemolysis and a reduction in the levels of SM and formation of ceramide and sphingosine 1-phosphate (S1P). N-Oleoylethanolamine, a ceramidase inhibitor, inhibited the toxin-induced hemolysis and caused ceramide to accumulate in the toxin-treated cells. Furthermore, DL-threo-dihydrosphingosine and B-5354c, isolated from a novel marine bacterium, both sphingosine kinase inhibitors, blocked the toxin-induced hemolysis and production of S1P and caused sphingosine to accumulate. These observations suggest that the toxin-induced activation of the SM metabolic system is closely related to hemolysis. S1P potentiated the toxin-induced hemolysis of saponin-permeabilized erythrocytes but had no effect on that of intact cells. Preincubation of lysated sheep erythrocytes with pertussis toxin blocked the ␣-toxininduced formation of ceramide from SM. In addition, incubation of C. botulinum C3 exoenzyme-treated lysates of sheep erythrocytes with ␣-toxin caused an accumulation of sphingosine and inhibition of the formation of S1P. These observations suggest that the ␣-toxininduced hemolysis of sheep erythrocytes is dependent on the activation of the SM metabolic system through GTP-binding proteins, especially the formation of S1P.

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Section: ␣-Toxin-induced Hemolysis and Sphingomyelin Metabolismmentioning

confidence: 99%

Clostridium perfringens α-Toxin Activates the Sphingomyelin Metabolism System in Sheep Erythrocytes

Ochi

Oda

Matsuda

et al. 2004

Journal of Biological Chemistry

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“…Direct Depletion of ER Calcium Stores Activates S1P Synthesis-The stimulation of S1P production from sphingosine by GPC agonists is well known (39,40), but if S1P links store depletion to SOCE, then direct store depletion should elicit S1P synthesis. This has not been examined.…”

Section: Fig 2 S1p Does Not Induce Emptying Of Pmn Calcium Storesmentioning

confidence: 99%

Sphingosine 1-Phosphate, a Diffusible Calcium Influx Factor Mediating Store-operated Calcium Entry

Itagaki

Hauser

2003

Journal of Biological Chemistry

108

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Store-operated calcium entry (SOCE) is a fundamental mechanism of calcium signaling. The mechanisms linking store depletion to SOCE remain controversial, hypothetically involving both diffusible messengers and conformational coupling of stores to channels. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that can signal via cell surface G-protein-coupled receptors, but S1P can also act as a second messenger, mobilizing calcium directly via unknown mechanisms. We show here that S1P opens calcium entry channels in human neutrophils (PMNs) and HL60 cells without prior store depletion, independent of G-proteins and of phospholipase C. S1P-mediated entry has the typical divalent cation permeability profile and inhibitor profile of SOCE in PMNs, is fully inhibited by 1 M Gd 3؉ , and is independent of [Ca 2؉ ] i . Depletion of PMN calcium stores by thapsigargin induces S1P synthesis. Inhibition of S1P synthesis by dimethylsphingosine blocks thapsigargin-, ionomycin-, and platelet-activating factor-mediated SOCE despite normal store depletion. We propose that S1P is a "calcium influx factor," linking calcium store depletion to downstream SOCE.Store-operated calcium entry (SOCE) 1 is the primary mechanism of regulated calcium entry into "non-excitable" cells like immunocytes. The mechanisms governing SOCE are controversial but have centered on two main hypotheses (1). In one model, emptying of endoplasmic reticulum (ER) calcium stores leads to the release of small diffusible messenger molecules that act on channels to increase Ca 2ϩ entry (2). Randriamampita and Tsien (3) found strong suggestions of such a messenger molecule in extracts from Jurkat T-cells. They termed this molecule "calcium influx factor" (CIF).Other hypotheses suggest that store depletion leads to calcium channel activation via direct physical interactions between cell membranes and intracellular structures. The "exocytosis model" (4, 5) of physical interactions suggests that vesicles bearing calcium channels fuse with the cell membrane after store depletion. The "conformational coupling" model suggests that ER calcium store depletion can lead to direct physical interactions between ER proteins such as the IP 3 receptor and cell membrane calcium channels such as TRPC3 (6, 7). No specific molecular mechanisms have been proposed however, that might initiate such physical interactions. Moreover, data has continued to accumulate supporting the existence of an unidentified, low molecular weight CIF (8, 9).Sphingosine 1-phosphate (S1P) is a universally bioactive, small (M r 380) sphingolipid metabolite. S1P is derived from the metabolism of sphingolipids and, most notably, from the actions of sphingosine kinase (10, 11) on sphingosine. In 1991, Zhang et al. (12) showed that S1P induces proliferation in Swiss 3T3 fibroblasts. Since that time, the actions of S1P have been studied in detail, and it has been found to be an important extracellular messenger molecule affecting cell growth, differentiation, adhesion, motility, and survival in many organ...

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“…In addition to its extracellular actions, S1P functions as a second messenger in the regulation of Ca 2+ homeostasis, 24,28,50,51 and suppression of apoptosis. 11,12,14,23,31,52 Although the intracellular targets of S1P remain to be identified, several lines of evidence support the second messenger role of S1P: (1) dihydro-S1P binds to and activates all of the identified S1PRs, but it does not mimic all of the effects of S1P, especially those related to cell survival; 30 (2) yeast cells do not possess GPCRs, yet the abundance of phosphorylated long-chain sphingoid bases regulates environmental stress responses, cell proliferation, and cell survival in a manner reminiscent of the function of S1P in mammalian cells; (3) in plants, which do not express S1PRs, S1P regulates Ca 2+ homeostasis and ion channels; 53 and (4) microinjection of S1P into, or photolysis of caged S1P within, mammalian cells induces both Ca 2+ mobilization 54 and cell proliferation.…”

Section: S1p As An Intracellular Second Messengermentioning

confidence: 99%

Sphingosine 1-phosphate as a therapeutic agent

2002

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The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P), formed by activation of sphingosine kinase in response to diverse stimuli, is an important lipid mediator that has novel dual actions -both inside and outside of cells. S1P is the ligand for a family of five G protein-coupled receptors. Activation of these GPCRs by S1P or dihydro-S1P regulates diverse processes, including cell migration, angiogenesis, vascular maturation, heart development, and neurite retraction. There is also abundant evidence that S1P can function as a second messenger important for regulation of calcium homeostasis, cell growth, and suppression of apoptosis. In many cases, the intracellular level of S1P and ceramide, another important sphingolipid metabolite associated with cell death and cell growth arrest, coordinately determine cell fate. Changes in S1P and ceramide have been implicated in a number of pathological conditions in which apoptosis plays an important role. Importantly, radiation-induced oocyte loss in adult female mice, the event that drives premature ovarian failure and infertility in female cancer patients, was completely prevented by in vivo therapy with S1P. Understanding the biosynthesis, metabolism and functions of S1P can uncover new targets for the pharmaceutical and therapeutic applications of S1P.

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Formyl Peptide Receptor Signaling in HL-60 Cells through Sphingosine Kinase

Cited by 100 publications

References 33 publications

Clostridium perfringens α-Toxin Activates the Sphingomyelin Metabolism System in Sheep Erythrocytes

Clostridium perfringens α-Toxin Activates the Sphingomyelin Metabolism System in Sheep Erythrocytes

Sphingosine 1-Phosphate, a Diffusible Calcium Influx Factor Mediating Store-operated Calcium Entry

Sphingosine 1-phosphate as a therapeutic agent

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