The bioactive phospholipid lysophosphatidic acid is released from activated platelets

Abstract

Lysophosphatidic acid (LPA) is a water-soluble phospholipid with hormone-like and growth-factor-like activities. LPA activates a putative G-protein-coupled receptor in responsive cells, but the natural source of exogenous LPA is unknown. Here we show that LPA is present in mammalian serum in an active form (bound to albumin) at concentrations of 1-5 microM, but is not detectable in platelet-poor plasma, suggesting that LPA is produced during blood clotting. We find that thrombin activation of platelets prelabelled with [32P]Pi results in the rapid release of newly formed [32P]LPA into the extracellular environment. We conclude that LPA is a novel platelet-derived lipid mediator that may play a role in inflammatory and proliferative responses to injury.

Lysophosphatidic acid inhibits gap-junctional communication and stimulates phosphorylation of connexin-43 in WB cells: possible involvement of the mitogen-activated protein kinase cascade

“…This simple phospholipid has all the hallmarks of a new class of signalling molecule, and it will be of great interest to determine whether LPA or PA generated metabolically have similar signalling functions. However the observations that serum contains LPA [28], and that activated platelets secrete the phospholipid, suggest that a model involving interaction with a surface receptor is physiologically feasible. It is also of considerable interest that LPA activates the MAP kinase cascade (see also [12]), raising the possibility that a kinase associated with this cascade is responsible for Cx43 phosphorylation.…”

Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid

“…This variation in protocol might account for Supplemental Material can be found at: ( 74 ). Following CNS injury, ischemia, or events that damage the blood brain barrier, LPA-like activity increased within the cerebrospinal fl uid , levels of LPA within the CNS increased up to 10 µM (75)(76)(77)(78), and levels of ATX increased within astrocytes neighboring a lesion of the adult rat brain ( 79 ). Our data using human cells suggest that the presence of LPA in regions of neurogenesis within the CNS may modify NS/PC survival and differentiation.…”

Human Lysophosphatidic Acid Acyltransferase

“…Because activated platelets copiously secrete the mediator, it has been suggested that aggregated platelets are the primary source of the serum LPA (14,18). This source, coupled with the mitogenic and chemotactic properties of LPA, has prompted the hypothesis that the phospholipid is an important mediator of wound healing (12). Additionally, several of the known effects of LPA are consistent with a potential proinflammatory or proimmune function.…”

“…During membrane phospholipid biosynthesis, LPA is formed by acylation of sn-glycerol-3-phosphate or by acylation of dihydroxyacetone phosphate followed by reduction of the acyl-dihydroxyacetone phosphate (10). In contrast, LPA that is rapidly generated in the plasma membrane of thrombin-activated platelets and growth factorstimulated fibroblasts (11,12) appears to arise from hydrolysis of phosphatidic acid (PA) by a phospholipase A 2 (13)(14)(15). Additionally, Fourcade et al (16) have demonstrated that a secretory phospholipase A 2 acts upon membrane microvesicles shed from activated cells to convert PA to LPA.…”