Sphingosine 1-Phosphate and Sphingosine Kinase Activity during Chicken Embryonic Development

ABSTRACT Sphingosine kinase has been recognized as an essential signaling molecule that mediates the intracellular conversion of sphingosine to sphingosine-1-phosphate. In mast cells, induction of sphingosine kinase and generation of sphingosine-1-phosphate have been linked to the initial rise in Ca2+, released from internal stores, and to degranulation. These events either precede or are concomitant with the activation of phospholipase C-γ and the generation of inositol trisphosphate. Here we show that sphingosine kinase type 1 (SPHK1) interacts directly with the tyrosine kinase Lyn and that this interaction leads to the recruitment of this lipid kinase to the high-affinity receptor for immunoglobulin E (FcεRI). The interaction of SPHK1 with Lyn caused enhanced lipid and tyrosine kinase activity. After FcεRI triggering, enhanced sphingosine kinase activity was associated with FcεRI in sphingolipid-enriched rafts of mast cells. Bone marrow-derived mast cells from Lyn−/ − mice, compared to syngeneic wild-type cells, were defective in the initial induction of SPHK1 activity, and the defect was overcome by retroviral Lyn expression. These findings position the activation of SPHK1 as an FcεRI proximal event.

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Epithelial cell extrusion requires the sphingosine-1-phosphate receptor 2 pathway

The Journal of Cell Biology ◽

10.1083/jcb.201010075 ◽

2011 ◽

Vol 193 (4) ◽

pp. 667-676 ◽

Cited By ~ 90

Author(s):

Yapeng Gu ◽

Tetyana Forostyan ◽

Roger Sabbadini ◽

Jody Rosenblatt

Keyword(s):

Stem Cells ◽

Epithelial Cell ◽

Kinase Activity ◽

Apoptotic Cell ◽

Sphingosine Kinase ◽

Live Cells ◽

Sphingosine 1 Phosphate ◽

A Cell ◽

Dying Cells ◽

Cell Extrusion

To maintain an intact barrier, epithelia eliminate dying cells by extrusion. During extrusion, a cell destined for apoptosis signals its neighboring cells to form and contract a ring of actin and myosin, which squeezes the dying cell out of the epithelium. Here, we demonstrate that the signal produced by dying cells to initiate this process is sphingosine-1-phosphate (S1P). Decreasing S1P synthesis by inhibiting sphingosine kinase activity or by blocking extracellular S1P access to its receptor prevented apoptotic cell extrusion. Extracellular S1P activates extrusion by binding the S1P2 receptor in the cells neighboring a dying cell, as S1P2 knockdown in these cells or its loss in a zebrafish mutant disrupted cell extrusion. Because live cells can also be extruded, we predict that this S1P pathway may also be important for driving delamination of stem cells during differentiation or invasion of cancer cells.

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Sphingosine Kinase Activity and Sphingosine-1 Phosphate Production in Rat Pancreatic Islets and INS-1 Cells: Response to Cytokines

Diabetes ◽

10.2337/diabetes.54.5.1429 ◽

2005 ◽

Vol 54 (5) ◽

pp. 1429-1436 ◽

Cited By ~ 50

Author(s):

L. D. Mastrandrea ◽

S. M. Sessanna ◽

S. G. Laychock

Keyword(s):

Pancreatic Islets ◽

Kinase Activity ◽

Sphingosine Kinase ◽

Rat Pancreatic Islets ◽

Sphingosine 1 Phosphate

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Regulation of the metabolism of apolipoprotein M and sphingosine 1-phosphate by hepatic PPARγ activity

Biochemical Journal ◽

10.1042/bcj20180052 ◽

2018 ◽

Vol 475 (12) ◽

pp. 2009-2024 ◽

Cited By ~ 6

Author(s):

Makoto Kurano ◽

Hitoshi Ikeda ◽

Naoyuki Iso-O ◽

Masumi Hara ◽

Kazuhisa Tsukamoto ◽

...

Keyword(s):

Hepg2 Cells ◽

Mouse Liver ◽

Kinase Activity ◽

Sphingosine Kinase ◽

Peroxisome Proliferator ◽

Obese Mice ◽

Peroxisome Proliferator Activated Receptor ◽

Apolipoprotein M ◽

Adenoviral Gene Transfer ◽

Sphingosine 1 Phosphate

Apolipoprotein M (apoM) is a carrier and a modulator of sphingosine 1-phosphate (S1P), an important multifunctional bioactive lipid. Since peroxisome proliferator-activated receptor γ (PPARγ) is reportedly associated with the function and metabolism of S1P, we investigated the modulation of apoM/S1P homeostasis by PPARγ. First, we investigated the modulation of apoM and S1P homeostasis by the overexpression or knockdown of PPARγ in HepG2 cells and found that both the overexpression and the knockdown of PPARγ decreased apoM expression and S1P synthesis. When we activated or suppressed the PPARγ more mildly with pioglitazone or GW9662, we found that pioglitazone suppressed apoM expression and S1P synthesis, while GW9662 increased them. Next, we overexpressed PPARγ in mouse liver through adenoviral gene transfer and observed that both the plasma and hepatic apoM levels and the plasma S1P levels decreased, while the hepatic S1P levels increased, in the presence of enhanced sphingosine kinase activity. Treatment with pioglitazone decreased both the plasma and hepatic apoM and S1P levels only in diet-induced obese mice. Moreover, the overexpression of apoM increased, while the knockdown of apoM suppressed PPARγ activities in HepG2 cells. These results suggested that PPARγ regulates the S1P levels by modulating apoM in a bell-shaped manner, with the greatest levels of apoM/S1P observed when PPARγ was mildly expressed and that hepatic apoM/PPARγ axis might maintain the homeostasis of S1P metabolism.

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Erythrocytes increase endogenous sphingosine 1-phosphate (S1P) levels as an adaptive response to SARS-CoV-2 infection

Clinical Science ◽

10.1042/cs20210666 ◽

2021 ◽

Author(s):

Martin Sebastian Winkler ◽

Ralf A Claus ◽

Mareike Schilder ◽

Stefan Pöhlmann ◽

Sina Coldewey ◽

...

Keyword(s):

Cell Culture ◽

Blood Cells ◽

Adaptive Response ◽

Kinase Activity ◽

Density Lipoprotein ◽

Sphingosine Kinase ◽

Healthy Controls ◽

Sphingosine Kinase 1 ◽

Adaptive Mechanisms ◽

Sphingosine 1 Phosphate

Low plasma levels of the signaling lipid metabolite sphingosine 1-phosphate (S1P) are associated with disrupted endothelial cell barriers, lymphopenia and reduced responsivity to hypoxia. Total S1P levels were also reduced in 23 critically ill patients with coronavirus disease 2019 (COVID-19), and the two main S1P carrier serum albumin (SA) and high-density lipoprotein (HDL) were dramatically low. Surprisingly, we observed a carrier changing shift from SA to HDL, which probably prevented an even further drop of S1P levels. Furthermore, intracellular S1P levels in red blood cells (RBC) were significantly increased in COVID-19 patients compared to healthy controls due to upregulation of S1P producing sphingosine kinase 1 and downregulation of S1P degrading lyase expression. Cell culture experiments supported increased sphingosine kinase activity and unchanged S1P release from RBC stores of COVID-19 patients. These observations suggest adaptive mechanisms for maintenance of the vasculature and immunity as well as prevention of tissue hypoxia in COVID-19 patients.

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Sphingosine kinase activity and sphingosine‐1‐phosphate in the inflamed human periodontium.

Oral Diseases ◽

10.1111/odi.13995 ◽

2021 ◽

Author(s):

Nader Hamdan ◽

Anjali Y. Bhagirath ◽

Eraldo L. Batista

Keyword(s):

Kinase Activity ◽

Sphingosine Kinase ◽

Sphingosine 1 Phosphate

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Apoptotic cell extrusion depends on single-cell synthesis of sphingosine-1-phosphate by sphingosine kinase 2

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ◽

10.1016/j.bbalip.2021.158888 ◽

2021 ◽

Vol 1866 (4) ◽

pp. 158888

Author(s):

Bruno Jaime Santacreu ◽

Daniela Judith Romero ◽

Lucila Gisele Pescio ◽

Estefanía Tarallo ◽

Norma Beatriz Sterin-Speziale ◽

...

Keyword(s):

Single Cell ◽

Apoptotic Cell ◽

Sphingosine Kinase ◽

Sphingosine Kinase 2 ◽

Sphingosine 1 Phosphate ◽

Cell Synthesis ◽

Cell Extrusion

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The control of the balance between ceramide and sphingosine-1-phosphate by sphingosine kinase: Oxidative stress and the seesaw of cell survival and death

Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology ◽

10.1016/j.cbpb.2012.05.006 ◽

2012 ◽

Vol 163 (1) ◽

pp. 26-36 ◽

Cited By ~ 117

Author(s):

James R. Van Brocklyn ◽

Joseph B. Williams

Keyword(s):

Oxidative Stress ◽

Cell Survival ◽

Sphingosine Kinase ◽

Sphingosine 1 Phosphate

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Mice Deficient in Sphingosine Kinase 1 Are Rendered Lymphopenic by FTY720

Journal of Biological Chemistry ◽

10.1074/jbc.m406512200 ◽

2004 ◽

Vol 279 (50) ◽

pp. 52487-52492 ◽

Cited By ~ 339

Author(s):

Maria L. Allende ◽

Teiji Sasaki ◽

Hiromichi Kawai ◽

Ana Olivera ◽

Yide Mi ◽

...

Keyword(s):

Vascular Development ◽

Sphingosine Kinase ◽

Sphingosine Kinase 1 ◽

Cellular Functions ◽

Lymphocyte Trafficking ◽

Signaling Molecule ◽

Physiological Functions ◽

Sphingosine 1 Phosphate ◽

Sphingosine Kinases ◽

S1p Receptor

Sphingosine-1-phosphate (S1P), a lipid signaling molecule that regulates many cellular functions, is synthesized from sphingosine and ATP by the action of sphingosine kinase. Two such kinases have been identified, SPHK1 and SPHK2. To begin to investigate the physiological functions of sphingosine kinase and S1P signaling, we generated mice deficient in SPHK1.Sphk1null mice were viable, fertile, and without any obvious abnormalities. Total SPHK activity in mostSphk1-/-tissues was substantially, but not completely, reduced indicating the presence of multiple sphingosine kinases. S1P levels in most tissues from theSphk1-/- mice were not markedly decreased. In serum, however, there was a significant decrease in the S1P level. Although S1P signaling regulates lymphocyte trafficking, lymphocyte distribution was unaffected in lymphoid organs ofSphk1-/- mice. The immunosuppressant FTY720 was phosphorylated and elicited lymphopenia in theSphk1null mice showing that SPHK1 is not required for the functional activation of this sphingosine analogue prodrug. The results with theseSphk1null mice reveal that some key physiologic processes that require S1P receptor signaling, such as vascular development and proper lymphocyte distribution, can occur in the absence of SPHK1.

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