Lysophosphatidylcholine induces arachidonic acid release and calcium overload in cardiac myoblastic H9c2 cells

Golfman, Leonard S.; Haughey, Norman J.; Wong, Johnson; Jiang, Jenny Y.; Lee, Douglas S.; Geiger, Jonathan D.; Choy, Patrick C.

doi:10.1016/s0022-2275(20)34898-7

Cited by 28 publications

(8 citation statements)

References 44 publications

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“…An additional mechanism involved in cPLA 2 activation is mediated via the G-proteins, which regulate the MAP kinase cascade (14). We have reported previously that lyso-PC is a potent activator of the cPLA 2 activity in both human endothelial cells and rat cardiac myoblastic H9c2 cells (28,29). In these studies, we have shown that the lyso-PC exerted its effect through mechanisms of post-transcriptional regulation.…”

Section: Discussionmentioning

confidence: 84%

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Modulation of cytosolic phospholipase A2 by PPAR activators in human preadipocytes

Jiang

Hatch

Mymin

et al. 2001

Journal of Lipid Research

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Cytosolic phospholipase A 2 (cPLA 2 ) is responsible for the release of arachidonic acid, a precursor for eicosanoid biosynthesis, from cellular phospholipids. The objective of this study is to examine the regulation of cPLA 2 by peroxisome proliferator-activated receptor (PPAR) activators in preadipocyte SW872 (SW) cells. PPAR belong to the superfamily of nuclear hormone receptors that heterodimerize with the retinoid X receptor. In this study, the presence of both PPAR ␣ and PPAR ␥ was confirmed in SW cells by positive identification of their mRNA in the cellular homogenate. Clofibrate, a PPAR ␣ activator, caused an enhancement of ionophore A-23187-induced arachidonate release in SW cells. This increase resulted from an enhancement of cPLA 2 activity, which was caused by an increase in enzyme protein. Clofibrate at lower concentrations (10-200 M) produced increases in the mRNA levels of cPLA 2 in a dose-response manner. At higher concentrations ( Ͼ 400 M), clofibrate treatment resulted in the attenuation of the cPLA 2 mRNA level and protein expression. We postulate that clofibrate, acting through the PPAR ␣ , caused an induction in the transcription of cPLA 2 gene, which led to an increase in the cPLA 2 protein. The observed increase in arachidonate release in SW cells appeared to be a direct result of the enhanced cPLA 2 activity. -Jiang, Y.

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Section: Discussionmentioning

confidence: 84%

“…We reported previously that lysophosphatidylcholine caused an elevation of cellular Ca 2 ϩ and the activation of protein kinase C, which resulted in an increased release of arachidonate in endothelial cells (28) and in H9c2 cells (29). In the current study, the regulation of cPLA 2 for the release of arachidonic acid by PPAR ␣ was investigated.…”

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confidence: 80%

Modulation of cytosolic phospholipase A2 by PPAR activators in human preadipocytes

Jiang

Hatch

Mymin

et al. 2001

Journal of Lipid Research

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“…We also observed increased levels of several fatty acids, such as palmitic acid, which can induce inflammatory responses [ 50 , 51 ] and might be related to the elevated level of AA. Previous studies have shown the increase in plasma lysoPCs, namely, palmitoyl (C16:0) and stearoyl (C18:0) acyl chains, greatly enhances AA release from membranes [ 52 , 53 ]. Elevated levels of cholesterol, glucose, and glycerol in OVX rat have been observed in previous metabolomics studies conducted in rats with OVX-induced obesity and bone loss [ 5 , 6 ].…”

Section: Discussionmentioning

confidence: 99%

Lowering of lysophosphatidylcholines in ovariectomized rats by Curcuma comosa

et al. 2022

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Decline of ovarian function in menopausal women increases metabolic disease risk. Curcuma comosa extract and its major compound, (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD), improved estrogen-deficient ovariectomized (OVX) rat metabolic disturbances. However, information on their effects on metabolites is limited. Here, we investigated the impacts of C. comosa ethanol extract and DPHD on 12-week-old OVX rat metabolic disturbances, emphasizing the less hydrophobic metabolites. Metabolomics analysis of OVX rat serum showed a marked increase compared to sham-operated rat (SHAM) in levels of lysophosphatidylcholines (lysoPCs), particularly lysoPC (18:0) and lysoPC (16:0), and of arachidonic acid (AA), metabolites associated with inflammation. OVX rat elevated lysoPCs and AA levels reverted to SHAM levels following treatments with C. comosa ethanol extract and DPHD. Overall, our studies demonstrate the effect of C. comosa extract in ameliorating the metabolic disturbances caused by ovariectomy, and the elevated levels of bioactive lipid metabolites, lysoPCs and AA, may serve as potential biomarkers of menopausal metabolic disturbances.

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“…Lysoglycerophosphocholines (LysoPC) have been reported to increase in a model of myocardium starvation and ischemia and are markers for incident coronary heart disease (Ganna et al, 2014 ). The modulation of arachidonic acid release has been shown to be regulated by LysoPC levels in rat heart myoblastic H9c2 cells with an enhanced release of LysoPCs associated with palmitoyl (C16:0) or stearoyl (C18:0) groups (Golfman et al, 1999 ). The accumulation of LysoPCs has also been linked to dysrhythmia following ischaemia (Sobel et al, 1978 ).…”

Section: Discussionmentioning

confidence: 99%

Perturbations in cardiac metabolism in a human model of acute myocardial ischaemia

et al. 2021

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Introduction Acute myocardial ischaemia and the transition from reversible to irreversible myocardial injury are associated with abnormal metabolic patterns. Advances in metabolomics have extended our capabilities to define these metabolic perturbations on a metabolome-wide scale. Objectives This study was designed to identify cardiac metabolic changes in serum during the first 5 min following early myocardial ischaemia in humans, applying an untargeted metabolomics approach. Methods Peripheral venous samples were collected from 46 patients in a discovery study (DS) and a validation study (VS) (25 for DS, 21 for VS). Coronary sinus venous samples were collected from 7 patients (4 for DS, 3 for VS). Acute myocardial ischaemia was induced by transient coronary occlusion during percutaneous coronary intervention (PCI). Plasma samples were collected at baseline (prior to PCI) and at 1 and 5 min post-coronary occlusion. Samples were analyzed by Ultra Performance Liquid Chromatography-Mass Spectrometry in an untargeted metabolomics approach. Results The study observed changes in the circulating levels of metabolites at 1 and 5 min following transient coronary ischaemia. Both DS and VS identified 54 and 55 metabolites as significant (P < 0.05) when compared to baseline levels, respectively. Fatty acid beta-oxidation and anaerobic respiration, lysoglycerophospholipids, arachidonic acid, docosahexaenoic acid, tryptophan metabolism and sphingosine-1-phosphate were identified as mechanistically important. Conclusion Using an untargeted metabolomics approach, the study identified important cardiac metabolic changes in peripheral and coronary sinus plasma, in a human model of controlled acute myocardial ischaemia. Distinct classes of metabolites were shown to be involved in the rapid cardiac response to ischemia and provide insights into diagnostic and interventional targets.

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Lysophosphatidylcholine induces arachidonic acid release and calcium overload in cardiac myoblastic H9c2 cells

Cited by 28 publications

References 44 publications

Modulation of cytosolic phospholipase A2 by PPAR activators in human preadipocytes

Modulation of cytosolic phospholipase A2 by PPAR activators in human preadipocytes

Lowering of lysophosphatidylcholines in ovariectomized rats by Curcuma comosa

Perturbations in cardiac metabolism in a human model of acute myocardial ischaemia

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