Lysophosphatidylcholine increases cytosolic calcium in ventricular myocytes by direct action on the sarcolemma

Woodley, Susan; Ikenouchi, Hiroshi; Barry, William H.

doi:10.1016/0022-2828(91)90977-t

Cited by 48 publications

(14 citation statements)

References 23 publications

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“…Unlike the situation with erythrocytes, however, in which damage (cytolysis) was observed rapidly following exposure to the PL, epithelial damage and ciliary dysfunction occurred more slowly, being progressive over the 4-h incubation period. These observations suggest that ciliated epithelial cells may be more resistant to the cytolytic effects of PL than erythrocytes, with cellular dysfunction and damage resulting primarily from PLmediated interference with plasma membrane cation transporters such as Ca 2z -adenosine triphosphatase (ATPase) and Na z , K z -ATPase [18,20]. These direct, injurious effects of the PL on ciliated epithelium and erythrocytes were antagonized by preincubation of the strips or red cells with vitamin E. It has previously been reported that vitamin E complexes with, and neutralizes, LPC through two types of interaction, namely formation of a hydrogen bond between the vitamin E chromanol nucleus hydroxyl group and the carboxyl group of the lysophospholipid, and interaction of the acyl chains of the lysophospholipid with the chromanol nucleus methyl groups of vitamin E [17].…”

Section: Discussionmentioning

confidence: 99%

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Vitamin E attenuates the injurious effects of bioactive phospholipids on human ciliated epitheliumin vitro

Feldman

Anderson²,

Theron³

et al. 2001

Eur Respir J

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Bioactive phospholipids (PL), particularly lysophosphatidylcholine (LPC), are being increasingly implicated in the pathogenesis of various acute and chronic inflammatory disorders, particularly those of the airways, while there is emerging evidence that vitamin E may function as a natural antagonist of these lipid mediators of inflammation. The aims of this study were to document the effects of vitamin E on the inhibition of ciliary beating and damage to structural integrity of human ciliated epithelium induced by the PL, platelet-activating factor (PAF), lyso-PAF and LPC in vitro in relation to the anti-oxidative and membrane-stabilizing properties of the vitamin.Ciliary beat frequency was measured by a phototransistor technique, and damage to structural integrity assessed by a visual-scoring index, while superoxide production by polymorphonuclear leukocytes and membrane-stabilizing potential were measured using lucigenin-enhanced chemiluminescence and haemolytic procedures, respectively.All three PL caused inhibition of ciliary beating and structural damage to human ciliated epithelium by membrane-directed cytotoxic mechanisms, which were potentiated by human polymorphonuclear leukocytes due to induction of oxidant-mediated injury. Both direct and phagocyte-inflicted epithelial injury was attenuated by vitamin E. In haemolytic and chemiluminescence assays, vitamin E neutralized both the membrane-destabilizing and pro-oxidative actions of all three PL, while spectrophotometric analysis of mixtures of vitamin E with PAF, lyso-PAF and LPC revealed alterations in peak intensity, as well as peak shifts, indicative of physicochemical interactions between the vitamin and the PL.Vitamin E status may be a determinant of susceptibility to phospholipid-mediated airway inflammation and damage.

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Section: Discussionmentioning

confidence: 99%

“…These observations suggest either that the in vivo pro-inflammatory potential of PAF is overrated [16], or that the cytotoxic and pro-inflammatory actions of PAF may be independent of PAF receptors, resulting from nonspecific membrane disruptive mechanisms as appears to be the case with LPC [17,18].…”

mentioning

confidence: 84%

Vitamin E attenuates the injurious effects of bioactive phospholipids on human ciliated epitheliumin vitro

Feldman

Anderson²,

Theron³

et al. 2001

Eur Respir J

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“…LPC applied externally increases intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) in isolated cardiac myocytes (Sedlis et al, 1983;Woodley et al, 1991;Ver Donck et al, 1992;Hashizume and Abiko, 1996). Therefore, LPC is thought to be one of the causes of Ca 2ϩ overload and arrhythmia during cardiac ischemia and reperfusion (Hoque et al, 1995;Hashizume et al, 1998).…”

Section: Kinase Inhibitor (R)-(ϩ)-trans-n-(4-pyridyl)-4-(1-aminoethylmentioning

confidence: 99%

Inhibitory Effect of Fluvastatin on Lysophosphatidylcholine-Induced Nonselective Cation Current in Guinea Pig Ventricular Myocytes

Li¹,

Matsuoka²,

Suzuki³

et al. 2002

Mol Pharmacol

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“…5,6,20,24 14,15) and that LPC causes long lasting bursts of Na+ influx because of prolongation of the inactivation process of the Na+ channel.16) It is possible that LPC first increases the intracellular Na+ concentration in cardiac myocytes because of inhibition of Na+-K+ ATPase and the increased burst of the Na+ currents, and then produces Ca2+-overload via the Na+/Ca2+ exchange mechanism.27) The second possible mechanism is that LPC directly increases sarcolemmal permeability to Ca2+. Our study18) has revealed that LPC increases non-selective cation current including the Na+, K+ and Ca2+ currents, but it does not increase the Cl-current in guinea-pig ventricular myocytes.…”

Section: Why Is Lpc Important To Produce Ischemic Damage?mentioning

confidence: 99%

A New Approach to the Development of Anti-ischemic Drugs. Substances that Counteract the Deleterious Effect of Lysophosphatidylcholine on the Heart.

et al. 1997

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SUMMARYLysophosphatidylcholine (LPC) is an amphiphilic metabolite that can be produced from membrane-phospholipids by activation of phospholipase A2 (PLA2), and it accumulates in the heart during ischemia and reperfusion. It is known that LPC is an arrhythmogenic substance. Recent studies have revealed that LPC produces mechanical and metabolic derangements in perfused working rat hearts, and Ca2+-overload in isolated cardiac myocytes. Thus, LPC possesses an ischemia-like effect on the heart. LPC accumulated in the myocardium activates phospholipase A2, establishing a vicious circle; i.e. LPC itself has an ability to produce another LPC. Therefore, a drug that has an anti-LPC effect would protect or improve ischemia/reperfusion damage. This article will review the effect of LPC in relation to ischemia, and consider a possibility of developing new anti-ischemic drugs on the basis of the anti-LPC action. (Jpn Heart J 1997; 38: 11-25) Key words: Lysophosphatidylcholine, Free fatty acid, Ischemia reperfusion, anti-ischemic drugs SCHEMIA and reperfusion of the heart produce myocardial damage.Although the mechanism of ischemia/reperfusion damage of the heart is not well known, there is a common understanding that Ca2+-overload is the final step in the events induced by ischemia/reperfusion, and that the Ca2+-overload is probably responsible for the ischemia-reperfusion damage. By what mechanism does ischemia/reperfusion induce Ca2+-overload? There are some candidates for the etiology of ischemia/reperfusion-induced Ca2+-overload; one is reduction of the tissue levels of high-energy phosphates including adenosine triphosphateFrom the Department of Pharmacology, Asahikawa Medical College, Asahikawa, Japan, and 1Department of Pharmacology and Toxicology, University of Western Ontario, London , Ontario, Canada.Address for correspondence: Hiroko Hashizume, MD, Department of Pharmacology , Asahikawa Medical College, Nishikagura 4-5, Asahikawa 078, Japan.Received for publication January 12, 1996. Accepted January 19, 1996.11 12 HASHIZUME ET AL Jpn Heart J January 1997(ATP) and the other is production of free radicals. In this mini review we propose that lysophosphatidylcholine (LPC) is also one of the candidates responsible for Ca2+-overload during ischemia and reperfusion, and that substances that counteract the effect of LPC can be new anti-ischemic drugs.

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Lysophosphatidylcholine increases cytosolic calcium in ventricular myocytes by direct action on the sarcolemma

Cited by 48 publications

References 23 publications

Vitamin E attenuates the injurious effects of bioactive phospholipids on human ciliated epitheliumin vitro

Vitamin E attenuates the injurious effects of bioactive phospholipids on human ciliated epitheliumin vitro

Inhibitory Effect of Fluvastatin on Lysophosphatidylcholine-Induced Nonselective Cation Current in Guinea Pig Ventricular Myocytes

A New Approach to the Development of Anti-ischemic Drugs. Substances that Counteract the Deleterious Effect of Lysophosphatidylcholine on the Heart.

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