title: Lysophosphatidic acid produced by hen egg white lysophospholipase D induces vascular development on extraembryonic membranes.
abstract: Lysophosphatidic acid (lysoPtdOH), a lysophospholipid mediator, exerts diverse physiological effects, including angiogenesis, through its specific G-protein-coupled receptors. Previously, we showed that unfertilized hen egg white contains polyunsaturated fatty acid-rich lysoPtdOH and lysophospholipase D (lysoPLD). Here, we examined whether lysoPtdOH was produced by lysoPLD in the presence and absence of a hen fertilized ovum and what the physiological role of lysoPtdOH in hen egg white is. Mass spectrometry showed that fertilized hen egg white contained about 8 μM lysoPtdOH before incubation with an ovum, mainly comprised of 18:1- (12.6 %), 18:2- (37.8 %) and 20:4-molecular species (41.5 %). In an early gestation period, the lysoPtdOH was increased up to 9.6 μM, concomitant with a decrease in the level of polyunsaturated lysophosphatidylcholine (lysoPtdCho). Moreover, lysoPtdOH-degrading activities were found in egg white and the vitelline membrane, showing that these enzymes control lysoPtdOH levels in egg white. In an egg yolk angiogenesis assay, two lysoPtdOH receptor antagonists, Ki16425 and N-palmitoyl serine phosphoric acid (NASP), inhibited blood vessel formation induced by exogenously added 18:1-lysoPtdOH and its precursor lysoPtdCho on the hen yolk sac. Ki16425 and NASP also inhibited blood vessel formation in the chorioallantoic membrane (CAM). Furthermore, the relatively higher levels of LPA₁, LPA₂, LPA₄ and LPA₆ mRNA were present in the yolk sac and CAM. These results suggest that lysoPtdOH produced from lysoPtdCho by the action of lysoPLD in hen egg white is involved in the formation of blood vessel networks through several lysoPtdOH receptors on various extraembryonic membranes, including the yolk sac membrane and CAM.
authors: Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
authors: Junichi
authors: J
authors: Morishige
authors: Yoshihiro
authors: Y
authors: Uto
authors: Hitoshi
authors: H
authors: Hori
authors: Kiyoshi
authors: K
authors: Satouchi
authors: Tanihiro
authors: T
authors: Yoshiomoto
authors: Akira
authors: A
authors: Tokumura
mesh_terms: D000818:Animals; D002642:Chick Embryo; D002645:Chickens / Q000502:physiology*; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D004529:Egg White / Q000032:analysis*; D005321:Extraembryonic Membranes / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D005306:Fertilization; D008246:Lysophospholipids / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010063:Ovum / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015017:Yolk Sac / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D000099189:Lysophospholipase D
chemical_list: D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid
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