Lysolecithins as endothelium-dependent vascular smooth muscle relaxants that differ from endothelium-derived relaxing factor (nitric oxide)

Saito, Takashi; Wolf, Andreas; Menon, N. K.; Saeed, Maythem; Alves, Cléber R.; Bing, Richard J.

doi:10.1073/pnas.85.21.8246

Cited by 46 publications

(14 citation statements)

References 27 publications

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“…Previous studies failed to recognise the dual effects of 1palmitoyl-LPC in evoking both endothelium-dependent relaxation mediated by EDRF (Saito et al, 1988) as well as the inhibition of the relaxation elicited by ACh (Kugiyama et al, 1990;Yokoyama et al, 1990) as is reported here (Figures 2 and 3). One possible explanation for these dual actions is that LPC activates the endothelial cells and elevates intracellular Ca2 + to such an extent that they become refractory to stimulation by ACh.…”

Section: High-density Lipoprotein and Serum Albumin Inhibitory Effectmentioning

confidence: 40%

Oxidative modification of low‐density lipoproteins and the inhibition of relaxations mediated by endothelium‐derived nitric oxide in rabbit aorta

Plane

Bruckdorfer

Kerr

et al. 1992

British J Pharmacology

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1 The mechanism by which Cu2f-oxidized low-density lipoproteins (oxLDL) inhibit acetylcholine (ACh)-evoked relaxations mediated by endothelium-derived nitric oxide (EDRF) in rabbit aortic rings was investigated. The proposed role of lysophosphatidylcholine (LPC) in the inhibition was also studied. 2 The kinetics of lipid peroxidation of native low-density lipoproteins (LDL) from individual donors, as measured by changes in conjugated diene concentration, were related to the inhibitory effects of the resultant oxLDL. It was found that the more susceptible LDL was to oxidation, the greater the inhibition. 3 No correlation was found between the inhibitory effects of oxLDL and LPC content. 4 Synthetic 1-palmitoyl LPC produced an inhibition of ACh-induced relaxations and when added to precontracted rings evoked nitric oxide-mediated endothelium-dependent relaxation. This latter effect was not elicited by oxLDL.5 Synthetic 1-palmitoyl (10 uM) had no effect on relaxations evoked by glyceryl trinitrate in endothelium-denuded aortic rings in contrast to the inhibition found previously for oxLDL. 6 Concentrations of oxLDL and phospholipase A2-treated LDL which inhibited relaxation contained very different LPC concentrations. Unlike oxLDL, the inhibitory effects of phospholipase A2-treated LDL preparations were independent of the donors and showed no lag period. 7 We sugggest that there are differences in the mechanisms by which oxLDL and 1-palmitoyl LPC exert their inhibitory effects on relaxation. 8 The inhibition of relaxation by oxLDL (1-2 mg protein ml-1) was prevented by the presence of high-density lipoproteins (HDL; 1-2 mg protein ml-1). 9 It is proposed that prevention of the inhibition of relaxation by HDL is consistent with the inhibitory factor(s) being lipophilic constituents of oxLDL. However, variations in the inhibitory effects of oxLDL preparations are not due to differences in their LPC content and factors other than LPC must contribute to the inhibition.

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Section: High-density Lipoprotein and Serum Albumin Inhibitory Effectmentioning

confidence: 40%

Oxidative modification of low‐density lipoproteins and the inhibition of relaxations mediated by endothelium‐derived nitric oxide in rabbit aorta

Plane

Bruckdorfer

Kerr

et al. 1992

British J Pharmacology

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“…For example, lyso-PC increases intracellular Ca 2ϩ levels (43,73,74) and yet inhibits receptor-mediated Ca 2ϩ mobilization (52,74). It exhibits both vasorelaxant (75) and vasoconstrictive (23) properties. It perturbs nitric oxide synthase mRNA and protein levels in endothelial cells, and up-or down-regulation is dependent on the concentration and incubation conditions used in each study (76 -78).…”

Section: Lyso-pc-induced Arachidonate Release In Endothelial Cellsmentioning

confidence: 99%

Lysophosphatidylcholine Stimulates the Release of Arachidonic Acid in Human Endothelial Cells

Wong¹,

Tran²,

Pierce³

et al. 1998

Journal of Biological Chemistry

104

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Lysophosphatidylcholine (lyso-PC) is a product of phosphatidylcholine hydrolysis by phospholipase A 2 (PLA 2 ) and is present in cell membranes, oxidized lipoproteins, and atherosclerotic tissues. It has the ability to alter endothelial functions and is regarded as a causal agent in atherogenesis. In this study, the modulation of arachidonate release by lyso-PC in human umbilical vein endothelial cells was examined. Incubation of endothelial cells with lyso-PC resulted in an enhanced release of arachidonate in a time-and concentration-dependent manner. Maximum arachidonate release was observed at 10 min of incubation with 50 M lyso-PC. Lyso-PC species containing palmitoyl (C 16:0 ) or stearoyl (C 18:0 ) groups elicited the enhancement of arachidonate release, while other lysolipids such as lysophosphatidylethanolamine, lysophosphatidylserine, lysophosphatidylinositol, or lysophosphatidate were relatively ineffective. Lyso-PC-induced arachidonate release was decreased by treatment of cells with PLA 2 inhibitors such as para-bromophenacyl bromide and arachidonoyl trifluoromethyl ketone. Furthermore, arachidonate release was attenuated in cells grown in the presence of antisense oligodeoxynucleotides that specifically bind cytosolic PLA 2 mRNA. Treatment of cells with lyso-PC resulted in a translocation of PLA 2 activity from the cytosolic to the membrane fractions of cells. Lyso-PC induced a rapid influx of Ca 2؉ from the medium into the cells, with a simultaneous enhancement of protein kinase C (PKC) activity in the membrane fractions. The lyso-PC-induced arachidonate release was attenuated when cells were preincubated with specific inhibitors of PKC (staurosporine and Ro31-8220) or a specific inhibitor of mitogen-activated protein kinase/extracellular regulated kinase kinase (PD098059). Taken together, the results of this study show that lyso-PC caused the elevation of cellular Ca 2؉ and the activation of PKC, which stimulated cytosolic PLA 2 in an indirect manner and resulted in an enhanced release of arachidonate.

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“…Lysophospholipids are membrane-perturbing agents that can directly cause tissue injury [70]. In addition, these molecules increase endothelial and epithelial permeability and promote recruitment and activation of inflammatory cells [71, 72]. Therefore, generation of lysophospholipids may be an additional mechanism by which sPLA 2 s may contribute to inflammation and tissue damage.…”

Section: Role Of Spla2s In Inflammatory Reactions:in Vitro Studiesmentioning

confidence: 99%

Secretory Phospholipases A<sub>2</sub> as Multivalent Mediators of Inflammatory and Allergic Disorders

Granata

Balestrieri

Petraroli

et al. 2003

Int Arch Allergy Immunol

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Phospholipases A₂ (PLA₂s) are enzymes responsible for mobilization of fatty acids, including arachidonic acid (AA), from phospholipids. These enzymes are classified as high-molecular-weight cytosolic PLA₂s (cPLA₂s) and low-molecular-weight secretory PLA₂s (sPLA₂s). There is increasing evidence that large quantities of sPLA₂s are released in the plasma of patients with systemic inflammatory and autoimmune diseases. In addition, high levels of sPLA₂s can be detected at sites of allergic inflammation including the upper airways of patients with rhinitis and the lower airways of patients with asthma. These extracellular enzymes play an important role in inflammation by releasing AA, which can be subsequently converted to proinflammatory prostaglandins and leukotrienes. Generation of AA mediated by sPLA₂s occurs through different mechanisms, including (1) the direct hydrolysis of outer cell membrane phospholipids, (2) internalization and transfer of sPLA₂s to intracellular pools of phospholipids enriched in AA, and (3) activation of cPLA₂s. In addition, sPLA₂s induce degranulation and production of cytokines and chemokines from a variety of cells involved in inflammatory and immune responses. These effects are exerted by mechanisms that are independent of the enzymatic activity and are mediated by the interaction of sPLA₂s with specific or promiscuous membrane receptors. Therefore, sPLA₂s may have an important role in inflammatory and allergic reactions by activating multiple mechanisms within inflammatory and immune cells, leading to the production of eicosanoids, cytokines and chemokines.

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Lysolecithins as endothelium-dependent vascular smooth muscle relaxants that differ from endothelium-derived relaxing factor (nitric oxide)

Cited by 46 publications

References 27 publications

Oxidative modification of low‐density lipoproteins and the inhibition of relaxations mediated by endothelium‐derived nitric oxide in rabbit aorta

Oxidative modification of low‐density lipoproteins and the inhibition of relaxations mediated by endothelium‐derived nitric oxide in rabbit aorta

Lysophosphatidylcholine Stimulates the Release of Arachidonic Acid in Human Endothelial Cells

Secretory Phospholipases A<sub>2</sub> as Multivalent Mediators of Inflammatory and Allergic Disorders

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