Stimulation of Sphingosine-1-phosphate Formation by the P2Y2Receptor in HL-60 Cells: Ca2+Requirement and Implication in Receptor-Mediated Ca2+Mobilization, but Not MAP Kinase Activation

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

doi:10.1124/mol.58.3.491

Cited by 41 publications

(26 citation statements)

References 34 publications

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“…In contrast, S1P 3 mRNA levels were reduced by almost 50% on days 15, 17, and 19 compared with day 1. There were no significant changes in the expression of S1P 2 .…”

Section: Resultsmentioning

confidence: 82%

“…Because little is known about key steps in the regulation of uterine lysophospholipid production, we examined steady-state mRNA levels of enzymes directly involved in the synthesis and degradation of LPA and Sph-1-P. Of the mRNA pool sizes of the LPA synthesis enzymes lysophospholipase D (autotaxin) and cPLA 2 , and the degradative enzymes LPP1 and LYP2, respectively, only that of LPP1 was elevated, about twofold, on days 15 and 17 of pregnancy compared with day 1 (Fig. 1B).…”

Section: Resultsmentioning

confidence: 99%

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Progesterone-induced sphingosine kinase-1 expression in the rat uterus during pregnancy and signaling consequences

Jeng¹,

Suarez²,

Izban³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Jeng YJ, Suarez VR, Izban MG, Wang HQ, Soloff MS. Progesterone-induced sphingosine kinase-1 expression in the rat uterus during pregnancy and signaling consequences. Am J Physiol Endocrinol Metab 292: E1110 -E1121, 2007. First published December 12, 2006; doi:10.1152/ajpendo.00373.2006.-Sphingosine 1-phosphate (Sph-1-P), a product of sphingomyelin metabolism, can act via a family of cognate G protein-coupled receptors or as an intracellular second messenger for agonists acting through their membrane receptors. In view of the general growth promoting and developmental effects of Sph-1-P on target cells, we hypothesized that it plays a role in adaptation of the uterus to pregnancy. We analyzed its potential role and that of the related lysophospholipid lysophosphatidic acid in the pregnant rat uterus by examining changes in mRNA levels of cognate receptors and enzymes involved in their turnover. Of these, only sphingosine kinase-1 (SphK1) was markedly changed (ϳ30-fold increase), being localized in the glandular epithelium, vasculature, and the myometrium. Uterine SphK1 mRNA and protein levels paralleled those of serum progesterone, and treatment with progesterone or an antagonist elevated or reduced SphK1 mRNA expression, respectively. Progesterone also increased SphK1 mRNA steady-state levels in a rat myometrial/leiomyoma cell line (ELT3). Overexpressing human SphK1 in these cells resulted in increased levels of the cell cycle regulator cyclin D1 and increased myosin light-chain phosphorylation. Ectopic expression of SphK1 also resulted in increased proliferation rates, possibly in conjunction with increased cyclin D1 expression. These studies suggest that the uterine expression of SphK1 mediates processes involved in growth and differentiation of uterine tissues during pregnancy. ELT3 cells; myosin light-chain phosphorylation; cyclin D1; lysophospholipids; sphingosine 1-phosphate; sphingosine-1-phosphate lyase THE BIOACTIVE LYSOPHOSPHOLIPIDS sphingosine 1-phosphate (Sph-1-P) and lysophosphatidic acid (LPA) are growth factors that act through a family of G protein-coupled receptors (GPCRs), S1P 1 through S1P 5 and LPA 1 through LPA 4 , respectively (25), causing a broad array of effects on target cells, including cell proliferation, survival, migration, adhesion molecule expression, and morphogenesis (26,31,44,47,52). Sph-1-P also plays a role in vasculogenesis in the mouse embryo (4, 27). Both lysophospholipids increase myosin lightchain phosphorylation in platelets and endothelial cells (10, 37) by inhibiting myosin light-chain phosphatase (43). They also stimulate DNA synthesis in human myometrial cells in primary culture (20,32). Platelets are the major source of circulating Sph-1-P and LPA, releasing the lysophospholipids in response to prothrombotic stimuli (47, 54). Circulating Sph-1-P also arises by constitutive secretion by cells of hemangioblastic lineage, such as monocytes, and by mast, endothelial, and red blood cells (54).Intracellular Sph-1-P is synthesized by a variety of cell types and acts as a...

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“…In contrast, S1P 3 mRNA levels were reduced by almost 50% on days 15, 17, and 19 compared with day 1. There were no significant changes in the expression of S1P 2 .…”

Section: Resultsmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Progesterone-induced sphingosine kinase-1 expression in the rat uterus during pregnancy and signaling consequences

Jeng¹,

Suarez²,

Izban³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

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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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“…These agonists induce calcium signaling by binding to a specific purinergic receptor of the P2Y 2 (previously called P 2U ) subtype (18,19). P2Y 2 receptors were shown previously to be present in HL-60 cells (22).…”

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confidence: 99%

Stimulation of Capacitative Calcium Entry in HL-60 Cells by Nanosecond Pulsed Electric Fields

White

Blackmore

Schoenbach

et al. 2004

Journal of Biological Chemistry

225

157

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Nanosecond pulsed electric fields (nsPEFs) are hypothesized to affect intracellular structures in living cells providing a new means to modulate cell signal transduction mechanisms. The effects of nsPEFs on the release of internal calcium and activation of calcium influx in HL-60 cells were investigated by using real time fluorescent microscopy with Fluo-3 and fluorometry with Fura-2. nsPEFs induced an increase in intracellular calcium levels that was seen in all cells. With pulses of 60 ns duration and electric fields between 4 and 15 kV/cm, intracellular calcium increased 200 -700 nM, respectively, above basal levels (ϳ100 nM), while the uptake of propidium iodide was absent. This suggests that increases in intracellular calcium were not because of plasma membrane electroporation. nsPEF and the purinergic agonist UTP induced calcium mobilization in the presence and absence of extracellular calcium with similar kinetics and appeared to target the same inositol 1,4,5-trisphosphate-and thapsigargin-sensitive calcium pools in the endoplasmic reticulum. For cells exposed to either nsPEF or UTP in the absence of extracellular calcium, there was an electric field-dependent or UTP dose-dependent increase in capacitative calcium entry when calcium was added to the extracellular media. These findings suggest that nsPEFs, like ligand-mediated responses, release calcium from similar internal calcium pools and thus activate plasma membrane calcium influx channels or capacitative calcium entry.

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Stimulation of Sphingosine-1-phosphate Formation by the P2Y₂Receptor in HL-60 Cells: Ca²⁺Requirement and Implication in Receptor-Mediated Ca²⁺Mobilization, but Not MAP Kinase Activation

Cited by 41 publications

References 34 publications

Progesterone-induced sphingosine kinase-1 expression in the rat uterus during pregnancy and signaling consequences

Progesterone-induced sphingosine kinase-1 expression in the rat uterus during pregnancy and signaling consequences

Sphingosine 1-phosphate as a therapeutic agent

Stimulation of Capacitative Calcium Entry in HL-60 Cells by Nanosecond Pulsed Electric Fields

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