title: Oleoyl-lysophosphatidylcholine limits endothelial nitric oxide bioavailability by induction of reactive oxygen species.
abstract: Previously we reported modulation of endothelial prostacyclin and interleukin-8 production, cyclooxygenase-2 expression and vasorelaxation by oleoyl- lysophosphatidylcholine (LPC 18:1). In the present study, we examined the impact of this LPC on nitric oxide (NO) bioavailability in vascular endothelial EA.hy926 cells. Basal NO formation in these cells was decreased by LPC 18:1. This was accompanied with a partial disruption of the active endothelial nitric oxide synthase (eNOS)- dimer, leading to eNOS uncoupling and increased formation of reactive oxygen species (ROS). The LPC 18:1-induced ROS formation was attenuated by the superoxide scavenger Tiron, as well as by the pharmacological inhibitors of eNOS, NADPH oxidases, flavin-containing enzymes and superoxide dismutase (SOD). Intracellular ROS-formation was most prominent in mitochondria, less pronounced in cytosol and undetectable in endoplasmic reticulum. Importantly, Tiron completely prevented the LPC 18:1-induced decrease in NO bioavailability in EA.hy926 cells. The importance of the discovered findings for more in vivo like situations was analyzed by organ bath experiments in mouse aortic rings. LPC 18:1 attenuated the acetylcholine-induced, endothelium dependent vasorelaxation and massively decreased NO bioavailability. We conclude that LPC 18:1 induces eNOS uncoupling and unspecific superoxide production. This results in NO scavenging by ROS, a limited endothelial NO bioavailability and impaired vascular function.
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, 8010 Graz, Austria.
authors.forename: Andrijana
authors.initials: A
authors.lastname: Kozina
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, 8010 Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Opresnik
authors.affiliation: Institute of Cardiovascular Physiology, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
authors.forename: Michael Sze Ka
authors.initials: MS
authors.lastname: Wong
authors.affiliation: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, 8010 Graz, Austria.
authors.forename: Seth
authors.initials: S
authors.lastname: Hallström
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, 8010 Graz, Austria.
authors.forename: Wolfgang F
authors.initials: WF
authors.lastname: Graier
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, 8010 Graz, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Malli
authors.affiliation: Institute of Cardiovascular Physiology, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schröder
authors.affiliation: Department of Pharmacology and Toxicology, Karl-Franzens-University of Graz, 8010 Graz, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Schmidt
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, 8010 Graz, Austria.
authors.forename: Saša
authors.initials: S
authors.lastname: Frank
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D008244:Lysophosphatidylcholines; D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III