Phosphatidic and lysophosphatidic acid production in phospholipase C-and thrombin-treated platelets. possible involvement of a platelet lipase

Mauco, Gérard; Chap, Hugues; Simon, Marie‐Pierre; Douste‐Blazy, Louis

doi:10.1016/s0300-9084(78)80784-6

Cited by 163 publications

(82 citation statements)

References 47 publications

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“…In the first pathway, LPA is converted from PA by PLA 1 or PLA 2 , which has been observed to occur in erythrocytes and ovarian cancer cells (12,13,33). In the second pathway, which may occur in platelets, diacylglycerol produced by PLC, could be deacylated by diacylglycerol lipase, with the resulting monoacylglycerol being further phosphorylated into LPA (34,35). The third pathway involves lysophospholipase D acting on LPC in plasma and may explain the large accumulation of LPA in aged plasma (14).…”

Section: Discussionmentioning

confidence: 99%

A Novel Phosphatidic Acid-selective Phospholipase A1That Produces Lysophosphatidic Acid

Sonoda

Aoki

Hiramatsu

et al. 2002

Journal of Biological Chemistry

192

182

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Lysophosphatidic acid (LPA) is a lipid mediator with diverse biological properties, although its synthetic pathways have not been completely solved. We report the cloning and characterization of a novel phosphatidic acid (PA)-selective phospholipase A 1 (PLA 1 ) that produces 2-acyl-LPA. The PLA 1 was identified in the GenBank TM data base as a close homologue of phosphatidylserine (PS)-specific PLA 1 (PS-PLA 1 ). When expressed in insect Sf9 cells, this enzyme was recovered from the Triton X-100-insoluble fraction and did not show any catalytic activity toward exogenously added phospholipid substrates. However, culture medium obtained from Sf9 cells expressing the enzyme was found to activate EDG7/LPA 3 , a cellular receptor for 2-acyl-LPA. The activation of EDG7 was further enhanced when the cells were treated with phorbol ester or a bacterial phospholipase D, suggesting involvement of phospholipase D in the process. In the latter condition, an increased level of LPA, but not other lysophospholipids, was confirmed by mass spectrometry analyses. Expression of the enzyme is observed in several human tissues such as prostate, testis, ovary, pancreas, and especially platelets. These data show that the enzyme is a membrane-associated PA-selective PLA 1 and suggest that it has a role in LPA production.

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Section: Discussionmentioning

confidence: 99%

A Novel Phosphatidic Acid-selective Phospholipase A1That Produces Lysophosphatidic Acid

Sonoda

Aoki

Hiramatsu

et al. 2002

Journal of Biological Chemistry

192

182

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“…However, the most important pathway is a multistep process linked to the activation of platelets (16)(17)(18)(19)(20)(21). This mechanism involves release of unidentifi ed PLA 1 and/or PLA 2 enzymes from activated platelets, thus generating a new pool of lysophospholipid (LPL) substrates, which in turn is cleaved by the lysophospholipase D autotaxin (ATX) ( 22,23 ).…”

Section: Measurement Of Phospholipase a 1 Activitymentioning

confidence: 99%

The phospholipase A1 activity of lysophospholipase A-I links platelet activation to LPA production during blood coagulation

Bolen¹,

Naren²,

Yarlagadda³

et al. 2011

Journal of Lipid Research

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Platelet activation initiates an upsurge in 18:2 and 20:4 lysophosphatidic acid (LPA) production. The biochemical pathway responsible for LPA production during blood clotting is not fully understood. We have purified a phospholipase A1 (PLA1) from thrombin‐activated human platelets using sequential chromatographic steps followed by fluorophosphonate‐biotin affinity labeling and proteomics. We identified acyl‐protein thioesterase 1 (aka. lysophospholipase A1, accession code ) as a novel PLA1. Addition of this recombinant PLA1 significantly increased the production of sn‐2‐esterified polyunsaturated LPCs and the corresponding LPAs in plasma. We next examined the regioisomeric preference of lysophospholipase D/autotaxin (ATX), which is the subsequent step in LPA production. To prevent acyl‐migration regioisomers of oleyl‐sn‐glycero‐3‐phosphocholine (LPAF) were synthesized. ATX preferred the sn‐1 over the sn‐2 regioisomer of LPAF. We propose the following LPA production pathway in blood: 1) Activated platelet secrete PLA1. 2) PLA1 generates a pool of sn‐2 lysophospholipids. 3) These newly generated sn‐2 lysophospholipids undergo acyl migration to yield sn‐1 lysophospholipids, which are the preferred substrates of ATX. 4) ATX cleaves the sn‐1 lysophospholipids to generate sn‐1 LPA species predominant with 18:2 and 20:4 fatty acids.

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“…LPA bioassays with Xenopus oocytes indicate 1-10 jiM LPA in the CSF in an animal model of hemorrhagic injury and even higher levels in the CSF following subarachnoid hemorrhage (Tigyi et al, 1995;Baybek et a!., 1996). Platelet aggregation is a potential source of LPA given the substantive release of LPA on platelet aggregation (Mauco et a!., 1978;Gerrard and Robinson, 1989;Eichho!tz eta!., 1993). The cells of the CNS are also likely to synthesize LPA, e.g., by the combined action of phospholipase D, to yield phosphatidic acid, followed by phospholipase A 2-mediated hydrolysis to give LPA.…”

Section: Lpa Induces a Decrease In Mitochondrial Membrane Potentialmentioning

confidence: 99%

Lysophosphatidic Acid Induces Necrosis and Apoptosis in Hippocampal Neurons

Holtsberg¹,

Steiner²,

Keller³

et al. 1998

Journal of Neurochemistry

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A diverse body of evidence indicates a role for the lipid biomediator lysophosphatidic acid (LPA) in the CNS. This study identifies and characterizes the induction of neuronal death by LPA. Treatment of cultured hippocampal neurons from embryonic rat brains with 50~eM LPA resulted in neuronal necrosis, as determined morphologically and by the release of lactate dehydrogenase. A concentration of LPA as low as 10~iMled to the release of lactate dehydrogenase. In contrast, treatment of neurons with 0.1 or 1.0 j.tM LPA resulted in apoptosis, as determined by chromatin condensation. In addition, neuronal death induced by 1 ,aM LPA was characterized as apoptotic on the basis of terminal dUTP nick end-labeling (TUNEL) staining, externalization of phosphatidylserme, and protection against chromatin condensation, TU N EL staining, and phosphatidylserine externalization by treatment with N-benzyloxycarbonyl-Val-Ala-Aspfluoromethyl ketone, a broad-spectrum inhibitor of caspases, i.e., members of the interleukin-1/3 converting enzyme family. Studies with antagonists of ionotropic glutamate receptors did not indicate a significant role for these receptors in apoptosis induced by 1 1iM LPA. LPA (1 1iM) also induced a decrease in mitochondrial membrane potential. Moreover, pretreatment of neurons with cyclosporin A protected against the LPA-induced decrease in mitochondrial membrane potential and neuronal apoptosis. Thus, LPA, at pathophysiological levels, can induce neuronal apoptosis and could thereby participate in neurodegenerative disorders. Key Words: Lysophosphatidic acid-Apoptosis-Neurons-Mitochondrial membrane potential -Cyclosporin A.

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Phosphatidic and lysophosphatidic acid production in phospholipase C-and thrombin-treated platelets. possible involvement of a platelet lipase

Cited by 163 publications

References 47 publications

A Novel Phosphatidic Acid-selective Phospholipase A1That Produces Lysophosphatidic Acid

A Novel Phosphatidic Acid-selective Phospholipase A1That Produces Lysophosphatidic Acid

The phospholipase A1 activity of lysophospholipase A-I links platelet activation to LPA production during blood coagulation

Lysophosphatidic Acid Induces Necrosis and Apoptosis in Hippocampal Neurons

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