Lysophosphatidic acid as a phospholipid mediator: pathways of synthesis

Gaits, Frédérique; Fourcade, Olivier; Balle, François Le; Gueguen, Geneviéve; Gaigé, Bernadette; Gassama‐Diagne, Ama; Fauvel, Josette; Salles, Jean‐Pierre; Mauco, Gérard; Simon, Marie‐Pierre; Chap, Hugues

doi:10.1016/s0014-5793(97)00411-0

Cited by 167 publications

(109 citation statements)

References 56 publications

(70 reference statements)

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“…Concentrations of 2.5 µM and 10 µM LPA were chosen because they seemed to be within the common range of concentrations used with other cell types [24,25] in addition to RBCs [17]. Moreover, this concentration is comparable to the local LPA concentration in the immediate surroundings of activated platelets, e.g., inside a blood clot [26,27]. While the choice of the LPA concentration did not seem to have any significant effect on the adhesion rate itself, it had an impact on the shape of the RBCs.…”

Section: Quantification Of the Intracellular Adhesionmentioning

confidence: 99%

Stimulation of human red blood cells leads to Ca2+-mediated intercellular adhesion

et al. 2011

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Red blood cells (RBCs) are a major component of blood clots, which form physiologically as a response to injury or pathologically in thrombosis. The active participation of RBCs in thrombus solidification has been previously proposed but not yet experimentally proven. Holographic optical tweezers and single-cell force spectroscopy were used to study potential cell-cell adhesion between RBCs. Irreversible intercellular adhesion of RBCs could be induced by stimulation with lysophosphatidic acid (LPA), a compound known to be released by activated platelets. We identified Ca 2+ as an essential player in the signaling cascade by directly inducing Ca 2+ influx using A23187. Elevation of the internal Ca 2+ concentration leads to an intercellular adhesion of RBCs similar to that induced by LPA stimulation. Using single-cell force spectroscopy, the adhesion of the RBCs was identified to be approximately 100 pN, a value large enough to be of significance inside a blood clot or in pathological situations like the vasco-occlusive crisis in sickle cell disease patients.

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Section: Quantification Of the Intracellular Adhesionmentioning

confidence: 99%

Stimulation of human red blood cells leads to Ca2+-mediated intercellular adhesion

et al. 2011

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“…LPA and S1P occur normally in serum and bind with high affinity to albumin, while retaining their biological activities. 12 Although these molecules exist in serum at concentrations of 2-20 mM, 13 their serum levels become increased in tumor-bearing patients. 14 LPA and S1P have been shown to have pleiotropic functions such as mitogenesis and angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Serum bioactive lysophospholipids prevent TRAIL-induced apoptosis via PI3K/Akt-dependent cFLIP expression and Bad phosphorylation

Kang

et al. 2004

Cell Death Differ

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Serum contains a variety of biomolecules, which play an important role in cell proliferation and survival. We sought to identify the serum factor responsible for mitigating tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis and to investigate its molecular mechanism. TRAIL induced effective apoptosis without serum, whereas bovine serum decreased apoptosis by suppressing cytochrome c release and caspase activation. Indeed, albumin-bound lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) inhibited TRAIL-induced apoptosis by suppressing caspase activation and cytochrome c release. LPA increased phosphatidylinositol 3-kinase (PI3K)-dependent Akt activation, cellular FLICE-inhibitory protein (cFLIP) expression, and Bad phosphorylation, resulting in inhibition of caspase-8 activation and Bad translocation to mitochondria. The antiapoptotic effect of LPA was abrogated by PI3K inhibitor, transfection with dominant-negative Akt, and specific downregulation of cFLIP expression using siRNA and further increased by siRNA-mediated suppression of Bad expression. Moreover, sera from ovarian cancer patients showed more protective effect against TRAIL-induced apoptosis than those from healthy donors, and this protection was suppressed by PI3K inhibitor. Our results indicate that albumin-bound LPA and S1P prevent TRAIL-induced apoptosis by upregulation of cFLIP expression and in part by Bad phosphorylation, through the activation of PI3K/Akt pathway.

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“…Bioactive LPA was initially found in culture serum (9) and was further detected in other biological fluids such as plasma (10,11), ascitic fluid (12), follicular fluid (13), aqueous humor (14), and the extracellular fluid of adipose tissue (5). Whereas serum LPA mainly originates from aggregating platelets (15,16), the precise cellular origin of LPA in other biological fluids still remains unclear.…”

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confidence: 99%

Autotaxin Is Released from Adipocytes, Catalyzes Lysophosphatidic Acid Synthesis, and Activates Preadipocyte Proliferation

Ferry

Tellier

Try

et al. 2003

Journal of Biological Chemistry

215

201

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Our group has recently demonstrated (Gesta, S., Simon, M., Rey, A., Sibrac, D., Girard, A., Lafontan, M., Valet, P., and Saulnier-Blache, J. S. (2002) J. Lipid Res. 43, 904 -910) the presence, in adipocyte conditioned-medium, of a soluble lysophospholipase D-activity (LPLDact) involved in synthesis of the bioactive phospholipid lysophosphatidic acid (LPA). In the present report, LPLDact was purified from 3T3F442A adipocyte-conditioned medium and identified as the type II ecto-nucleotide pyrophosphatase phosphodiesterase, autotaxin (ATX). A unique ATX cDNA was cloned from 3T3F442A adipocytes, and its recombinant expression in COS-7 cells led to extracellular release of LPLDact. ATX mRNA expression was highly up-regulated during adipocyte differentiation of 3T3F442A-preadipocytes. This up-regulation was paralleled by the ability of newly differentiated adipocytes to release LPLDact and LPA. Differentiation-dependent up-regulation of ATX expression was also observed in a primary culture of mouse preadipocytes. Treatment of 3T3F442A-preadipocytes with concentrated conditioned medium from ATX-expressing COS-7 cells led to an increase in cell number as compared with concentrated conditioned medium from ATX non-expressing COS-7 cells. The specific effect of ATX on preadipocyte proliferation was completely suppressed by co-treatment with a LPA-hydrolyzing phospholipase, phospholipase B. Finally, ATX expression was found in mature adipocytes isolated from mouse adipose tissue and was substantially increased in genetically obesediabetic db/db mice when compared with their lean siblings. In conclusion, the present work shows that ATX is responsible for the LPLDact released by adipocytes and exerts a paracrine control on preadipocyte growth via an LPA-dependent mechanism. Up-regulations of ATX expression with adipocyte differentiation and genetic obesity suggest a possible involvement of this released protein in the development of adipose tissue and obesity-associated pathologies.Because of its ability to store extra energy as triacylglycerol (lipogenesis) and to release fatty acids and glycerol (lipolysis), adipose tissue plays a crucial role in energy balance. In obesity, excessive accumulation of triacylglycerol in adipocytes (hypertrophy) results from an alteration in the balance between lipogenic and/or lipolytic activities of the adipocytes.It is now recognized that, beside their involvement in lipid homeostasis, adipocytes also produce and secrete numerous factors. Among them are endocrine peptides (leptin, adiponectin, angiotensinogen, etc.) which may play an important role in the development of morbid complications of obesity such as cardiovascular diseases, hypertension, diabetes, and cancer. Other adipocyte-secreted factors (tumor necrosis factor, fatty acids, eicosanoids, lysophosphatidic acid, etc.) are produced locally and may influence adipose tissue development and/or metabolism by exerting autocrine/paracrine effects on the different cells composing adipose tissue (adipocytes, preadipocytes, and endothelial...

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Lysophosphatidic acid as a phospholipid mediator: pathways of synthesis

Cited by 167 publications

References 56 publications

Stimulation of human red blood cells leads to Ca2+-mediated intercellular adhesion

Stimulation of human red blood cells leads to Ca2+-mediated intercellular adhesion

Serum bioactive lysophospholipids prevent TRAIL-induced apoptosis via PI3K/Akt-dependent cFLIP expression and Bad phosphorylation

Autotaxin Is Released from Adipocytes, Catalyzes Lysophosphatidic Acid Synthesis, and Activates Preadipocyte Proliferation

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