Palmitoyl lysophosphatidylcholine mediated mobilization of LPL to the coronary luminal surface requires PKC activation

Pulinilkunnil, Thomas; Ding, An; Yip, Patsy; Chan, Nathan; Qi, Dake; Ghosh, Sanjoy; Abrahani, Ashraf; Rodrigues, Brian

doi:10.1016/j.yjmcc.2004.07.003

Cited by 16 publications

(12 citation statements)

References 56 publications

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“…Heparan sulfate oligosaccharides, fragments of myocyte HSPG, have then been shown to act as extracellular chaperones for LPL, transporting the enzyme in its active form toward the apical surface of endothelial cells (36,38). Mediators responsible for the cleavage and transfer of LPL from the parenchymal cell surface to the lumen include the lipolytic byproduct lysoPC (41). At least in the whole heart, the LPL-augmenting property of lysoPC likely required endothelial PKC activation and formation of LPA (41).…”

Section: Discussionmentioning

confidence: 99%

“…Mediators responsible for the cleavage and transfer of LPL from the parenchymal cell surface to the lumen include the lipolytic byproduct lysoPC (41). At least in the whole heart, the LPL-augmenting property of lysoPC likely required endothelial PKC activation and formation of LPA (41). One of the best-characterized effects of LPA is actin cytoskeleton reassembly (2,32,56,59).…”

Section: Discussionmentioning

confidence: 99%

“…In coculture experiments, lysophosphatidylcholine (lysoPC) has been suggested to be one such mediator, which, by secreting heparanase-like compounds from endothelial cells, cleaves and transports adipocyte surface LPL to the endothelial apical surface (38). We have demonstrated that exposure of isolated control hearts to lysoPC also enhances luminal LPL (41,42). This LPL-augmenting property of lyso-PC likely required obligatory formation of lysophosphatidic acid (LPA), leading to mobilization of enzyme from the myocyte to the coronary lumen (41).…”

mentioning

confidence: 99%

“…This LPL-augmenting property of lyso-PC likely required obligatory formation of lysophosphatidic acid (LPA), leading to mobilization of enzyme from the myocyte to the coronary lumen (41). Indeed, when cardiomyocytes were incubated with LPA, myocyte surface LPL activity increased (41).…”

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confidence: 99%

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Lysophosphatidic acid-mediated augmentation of cardiomyocyte lipoprotein lipase involves actin cytoskeleton reorganization

Pulinilkunnil¹,

Ding²,

Ghosh³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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(J Mol Cell Cardiol 37: 931-938, 2004). Given that the actin cytoskeleton has been implicated in regulating cardiomyocyte LPL, we examined whether LPL secretion after LPA involves actin cytoskeleton reassembly. Incubation of myocytes with LPA (1-100 nM) increased basal and heparin-releasable LPL (HR-LPL), an effect that was independent of shifts in LPL mRNA. The influence of LPA on myocyte LPL was reflected at the coronary lumen, with substantial increases of the enzyme at this location. Incubation of myocytes with cytochalasin D not only blocked LPA-induced augmentation of HR-LPL but also abrogated filamentous actin formation. These effects of LPA were likely receptor mediated. Exposure of myocytes to LPA facilitated significant membrane translocation of RhoA and its downstream effector Rho kinase I (ROCK I), and blocking this effect with Y-27632 appreciably reduced basal and HR-LPL activity. Incubation of adipose tissue with LPA also significantly enhanced basal and HR-LPL activity, suggesting that sarcomeric actin likely has a limited role in influencing the LPL secretory function of LPA in the myocyte. Comparable to LPA, hyperglycemia also caused significant membrane translocation of RhoA and ROCK I in hearts isolated from diazoxidetreated animals, effects that were abrogated using insulin. Overall, our data suggest that comparable to hyperglycemia, LPA-induced increases in cardiac LPL occurred via posttranscriptional mechanisms and processes that likely required RhoA activation and actin polymerization. Whether this increase in LPL augments triglyceride deposition in the heart leading to eventual impairment in contractile function is currently unknown.RhoA; Rho kinase I; actin HEART DISEASE is a leading cause of mortality in diabetic patients, with coronary vessel disease being the primary reason for the increased incidence of cardiovascular dysfunction (27,52). More recent evidence suggests that heart failure during diabetes can also occur secondary to altered cardiac energy metabolism where impaired glucose transport and utilization switches ATP production exclusively to oxidation of fatty acids (FA) (48). This adaptive mechanism could eventually become counterproductive leading to "lipotoxicity" where FA accumulate and can, either by themselves or via production of second messengers such as ceramides, provoke cell death (28).Heart tissue acquires energy from metabolism of two major substrates, glucose and FA, the latter being the preferred substrate consumed (44,48). FA delivery to the heart involves 1) release from adipose tissue and transport to the heart after complexing with albumin (26), 2) provision through the breakdown of endogenous cardiac triglyceride (TG) stores (37), 3) internalization of whole lipoproteins (55), and 4) hydrolysis of circulating TG-rich lipoproteins to FA by coronary lumen lipoprotein lipase (LPL) (8). The molar concentration of FA bound to albumin is ϳ10-fold less than that of FA in lipoprotein-TG (30), and, recently, LPL-mediated hydrolysis of lipoproteins was suggested t...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Lysophosphatidic acid-mediated augmentation of cardiomyocyte lipoprotein lipase involves actin cytoskeleton reorganization

Pulinilkunnil¹,

Ding²,

Ghosh³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…glycerolipids can also regulate H-LPL activity: palmitoyl lyso-PC [69] and LPA [70] stimulate LPL translocation and activity. Cardiac LPL activity may be regulated directly: angptl-3 and angptl-4 are angiopoietin-like growth factor/cytokine related proteins secreted into plasma with pleiotropic effects, including inhibition of LPL [71].…”

Section: Lipoprotein Lipase Mediated Myocardial Tag Uptakementioning

confidence: 99%

The role of triacylglycerol in cardiac energy provision

Evans

Hui‐Kang

2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Triacylglycerols (TAG) constitute the main energy storage resource in mammals, by virtue of their high energy density. This in turn is a function of their highly reduced state and hydrophobicity.Limited water solubility, however, imposes specific requirements for delivery and uptake mechanisms on TAG-utilising tissues, including the heart, as well as intracellular disposition. TAGs constitute potentially the major energy supply for working myocardium, both through bloodborne provision and as intracellular TAG within lipid droplets, but also provide the heart with fatty acids (FA) which the myocardium cannot itself synthesise but are required for glycerolipid derivatives with (non-energetic) functions, including membrane phospholipids and lipid signalling molecules. Furthermore they serve to buffer potentially toxic amphipathic fatty acid derivatives.Intracellular handling and disposition of TAGs and their FA and glycerolipid derivatives similarly requires dedicated mechanisms in view of their hydrophobic character. Dysregulation of utilisation can result in inadequate energy provision, accumulation of TAG and/or esterified species, and these may be responsible for significant cardiac dysfunction in a variety of disease states. This review will focus on the role of TAG in myocardial energy provision, by providing FAs from exogenous and endogenous TAG sources for mitochondrial oxidation and ATP production, and how this can change in disease and impact on cardiac function. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 3Key words:heart; triacylglycerol; very-low-density lipoprotein; VLDL; chylomicron; lipid droplet Highlights: Triacylglycerols are supplied to the myocardium within chylomicrons and VLDL  Heart assimilates triacylglycerol-rich lipoproteins by LPL and receptor-mediated routes  Exogenous triacylglycerol-derived fatty acids enter an intracellular lipid pool  Intracardiac triacylglycerol is an important source of fatty acids for oxidation  Dysregulation of triacylglycerol metabolism is associated with cardiac dysfunction

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