Measurement of plasma lysophosphatidic acid concentration in healthy subjects: strong correlation with lysophospholipase D activity

Abstract

Background: Lysophosphatidic acid (LPA) plays important roles in a variety of biological responses, especially in the area of vascular biology, and the determination of its plasma concentration is believed to be important. Several mechanisms are known to be involved in the metabolism of LPA. Methods: To identify factors that may determine the plasma concentrations of this important bioactive lipid, we examined its concentrations using an enzymatic cycling assay and related parameters in 146 healthy subjects. Results: The LPA concentration was significantly higher in women (mean + SD, 0.103 + 0.032 mmol/L; n ¼ 47) than in men (0.077 + 0.026 mmol/L; n ¼ 99). A multiple regression analysis showed a strong positive correlation between the plasma LPA concentration and serum lysophospholipase D (lysoPLD) activity, while the LPA concentration was correlated with the plasma lysophosphatidylcholine (LPC) concentration only in men. Other lipid-related parameters were only slightly correlated or were not correlated with the LPA concentration. Conclusions: Our findings suggested that conversion from LPC by lysoPLD might be the major route for LPA production in plasma.

LPA receptor signaling: pharmacology, physiology, and pathophysiology

“…However, there is a growing range of recognized chemical forms of LPA in various biological systems (31,32) that have been observed in concentrations spanning low nanomolar to micromolar levels. LPA concentrations in blood can range from 0.1 M in plasma and up to 10 M in serum, which is well over the apparent nanomolar K d of LPA [1][2][3][4][5][6] (23,(33)(34)(35) (36)(37)(38). Aside from blood, LPA has been quantifi ed in a variety of species, tissues, and fl uids, including neural tissue, cerebrospinal fl uid (CSF), seminal fl uid, urine, saliva, and aqueous humor (7,36,(39)(40)(41)(42)(43)(44)(45) (Table 1).…”

“…Cmpd, compound; NPSPA, N-palmitoyl serine phosphoric acid; NPTyrPA, Npalmitoyl tyrosine phosphoric acid; NAEPA, N-acyl ethanolamide phosphate; AO-LPA 12b, sn-2-aminooxy analog 12b; a-FMP, ␣-fl uoromethylene phosphonate; a-HMP, ␣-hydroxymethylene phosphonate; TPA, thiophosphatidic acid; DDP, dodecyl phosphate; a-MP, ␣-methylene phosphonate; ODP, octadecenyl phosphate; TP 18:1, oleoyl-thiophosphate; BrP-LPA 19b, ␣-bromomethylene phosphonate analog 19b; TDP, tetradecyl phosphonate; FDP, farnesyl diphosphate. by guest, on www.jlr.org Downloaded from indirect enzymatic assays (34), TLC-GC, LC-MS, and LC-MS/MS (46)(47)(48). These techniques have a growing number of predictive, diagnostic, and therapeutic uses (29,43,49,50).…”

Lysophosphatidic Acid Signals through Multiple Receptors in Osteoclasts to Elevate Cytosolic Calcium Concentration, Evoke Retraction, and Promote Cell Survival

“…Materials-Medium 199 (M199) buffered with 25 mM HEPES and 26 mM HCO 3 Ϫ , HCO 3 Ϫ -free M199 buffered with 25 mM HEPES, ␣-minimum essential medium buffered with HCO 3 Ϫ (26 mM), heat-inactivated fetal bovine serum (FBS), antibiotic solution (penicillin 10,000 units/ml; streptomycin 10,000 g/ml; and amphotericin B 25 g/ml), fura-2 acetoxymethyl ester (fura-2 AM), and Alexa Fluor 488 phalloidin were purchased from Invitrogen. Bovine albumin (crystallized) was from ICN Biomedicals Inc. (Aurora, OH).…”

“…Lysophosphatidic acid (LPA) 5 is a potent bioactive phospholipid present at low levels in plasma (ϳ100 nM) (3) and elevated levels at sites of tissue injury and inflammation (3,4). Produced by several cell types including activated platelets, LPA signals through five well described G protein-coupled receptors, LPA 1 -LPA 5 , each of which can couple to multiple heterotrimeric G proteins (5).…”

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

“…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 ). As a result of this mechanism, plasma LPA concentration rises from a steady-state concentration of approximately 100 nM to serum concentrations up to 10 µM, with a significant increase in the content of polyunsaturated acyl species ( 19,24,25 ). The role of ATX in LPA production has been clearly demonstrated by the decreased plasma LPA level in ATX knockout mice ( 26,27 ).…”