Phospholipase D/phosphatidic acid signal transduction: Role and physiological significance in lung

Cummings, Rhett; Parinandi, Narasimham L.; Wang, Lixin; Usatyuk, Peter V.; Natarajan, Viswanathan

doi:10.1007/978-1-4615-1087-1_11

Cited by 33 publications

(53 citation statements)

References 84 publications

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“…Extracellularly, LPA can be produced by a secretory phospholipase A 2 (PLA 2 ) ( 13 ), oxidative modifi cation of low density lipoprotein ( 14 ), or by the action of phosphatidic acid-specifi c phospholipase A 1 ( 12,15 ). However, the most important pathway is a multistep process linked to the activation of platelets (16)(17)(18)(19)(20)(21).…”

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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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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“…LPA is released from activated platelets at sites of injury (Eichholtz et al, 1993) where it then contributes to wound repair (Lee et al, 2000), but it can also be synthesized by epithelial cells via the conversion of phosphatidic acid by phospholipase A 1 /A 2 (Cummings et al, 2002). LPA is increased in allergen-challenged lungs compared with saline controls (Georas et al, 2007), and it is 2-to 5-fold higher in injured, prefibrotic mouse lungs (Toews et al, 2004).…”

Section: N-[(2r)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl]-mentioning

confidence: 99%

Lysophosphatidic Acid Decreases Epidermal Growth Factor Receptor Binding in Airway Epithelial Cells

Kassel

Schulte

Parker

et al. 2007

J Pharmacol Exp Ther

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We showed previously that treatment of human airway smooth muscle cells and lung fibroblasts with lysophosphatidic acid (LPA) increases the binding of epidermal growth factor (EGF) to EGF receptors (EGFRs). The purpose of this study was to determine whether LPA also regulates EGFR binding in airway epithelial cells. Airway epithelial cells were incubated in the absence or presence of 10 M LPA for increasing times, and binding of 125

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“…Lipid-derived second messengers generated by the action of phospholipases on membrane-associated phospholipids play an important role in cellular signal transduction in general (3). Phospholipase D (PLD), which catalyzes the hydrolysis of phosphotidylcholine to phosphatidic acid (PA) and choline, has been recognized to be an intermediate in the actions of a wide variety of agonists on cellular functions, including those that cause proliferation (8,33).…”

mentioning

confidence: 99%

Phospholipase D signaling in serotonin-induced mitogenesis of pulmonary artery smooth muscle cells

Liu

Fanburg²

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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(7), has been increasingly associated with pulmonary hypertension (2, 4, 9, 30), and it is recognized that hyperplasia of SMCs accompanies the pathology of pulmonary hypertension (5, 10, 22). 5-HT initiates its SMC mitogenic action through both 5-HT receptors and the 5-HT transporter (5-HTT) (7) that are present on the cell membrane in close proximity to membrane structural lipids that include phosphatidylcholine. Through the receptor and transporter ligands, 5-HT produces SMC proliferation via combinatorial actions on the small G protein Rho, p 42/44 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3-kinase)/protein kinase B (Akt), and platelet-derived growth factor-␤ receptor signaling pathways (17-20).Lipid-derived second messengers generated by the action of phospholipases on membrane-associated phospholipids play an important role in cellular signal transduction in general (3). Phospholipase D (PLD), which catalyzes the hydrolysis of phosphotidylcholine to phosphatidic acid (PA) and choline, has been recognized to be an intermediate in the actions of a wide variety of agonists on cellular functions, including those that cause proliferation (8,33). Agonists identified to activate PLD include neurotransmitters, growth factors, hormones, calcium ionophores, and reactive oxygen species (6, 24). The cell signaling associated with PLD activation occurs at least in part through actions of PA (14).It previously was reported that 5-HT activates PLD in rat mesangial cells (15) and mesenteric SMCs, which associates the activation of PLD with contraction (11). Plevin and coworkers (27) demonstrated in 1994 that 5-HT activates PLD in cultured sheep pulmonary artery SMCs. However, there is no information currently available about the relationship between 5-HT, its receptors and transporter, and PLD in pulmonary artery SMC signaling and proliferation. In the present study, we show that 5-HT activates PLD of pulmonary artery SMCs via the 5-HT 2A receptor, leading to the generation of PA that promotes SMC proliferation through activations of mammalian target of rapamycin (mTOR), S6K1 and MAPK but not the Rho or PI3-kinase/Akt signaling pathways. We hypothesize that these observations link an important lipid component of the cell membrane, i.e., phosphatidyl choline, with cell signaling occurring via 5-HT ligands in SMCs.

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Phospholipase D/phosphatidic acid signal transduction: Role and physiological significance in lung

Cited by 33 publications

References 84 publications

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

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

Lysophosphatidic Acid Decreases Epidermal Growth Factor Receptor Binding in Airway Epithelial Cells

Phospholipase D signaling in serotonin-induced mitogenesis of pulmonary artery smooth muscle cells

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