Phospholipase A2-Mediated Activation of Phospholipase D in Rat Heart Sarcolemma

Liu, Song-Yan; Tappia, Paramjit S.; Dai, Jian; Williams, Sean A.; Panagia, Vincenzo

doi:10.1006/jmcc.1998.0685

Cited by 33 publications

(23 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27 Ang II-induced PLD activation was also abolished in the absence of extracellular calcium, and cPLA 2 activation was an early event compared with PLD stimulation in rabbit VSMCs (data not shown). It has been reported that the activation of PLD depends on cPLA 2 in rat heart sarcolemma, 13 leukocytes, 14 and HEK293 cells. 15 Supporting this hypothesis was our demonstration that the PLA 2 inhibitor MAFP 21 and cPLA 2 antisense blocked Ang II-induced PLD activation in rabbit VSMCs.…”

Section: Discussionmentioning

confidence: 98%

“…Recently, it was reported that cPLA 2 is involved in PLD activation in rat heart sarcolemma, 13 leukocyte cell lines, 14 and HEK293 cells. 15 To assess the contribution of cPLA 2 to Ang II-induced PLD activation, we used MAFP (50 mol/L), 21 a PLA 2 inhibitor, and HELSS (haloenol lactone suicide substrate), a selective calcium-independent PLA 2 (iPLA 2 ) inhibitor with a 1000-fold selectivity for iPLA 2 over cPLA 2 at 10 mol/L.…”

Section: Cpla 2 and Cytochrome P450 Product 20-hete Mediate Ang IImentioning

confidence: 99%

“…11 Ang II also activates ras/MAP kinase via arachidonic acid metabolites formed through CYP4A and lipoxygenase . 12 These observations, together with recent reports that the PLD activation in cardiac sarcolemma, 13 leukocytes, 14 and HEK 293 cells 15 is mediated through the stimulation of cPLA 2 , raised the possibility that the activation of PLD in VSMCs by Ang II might be mediated by the ras/MAP kinase pathway metabolites of arachidonic acid that are generated by the initial activation of cPLA 2 . To test this hypothesis, we examined the effect of various inhibitors of this pathway on Ang II-induced PLD activation in rabbit VSMCs.…”

mentioning

confidence: 92%

See 2 more Smart Citations

20-Hydroxyeicosatetraenoic Acid Mediates Angiotensin II–Induced Phospholipase D Activation in Vascular Smooth Muscle Cells

et al. 2001

View full text Add to dashboard Cite

Abstract-Angiotensin II (Ang II) activates cytosolic phospholipase A 2 (cPLA 2 ) and phospholipase D (PLD) in rabbit vascular smooth muscle cells (VSMCs). Ang II also activates ras/mitogen-activated protein (MAP) kinase in VSMCs; this activation is mediated by 20-hydroxyeicosatetraenoic acid (HETE) and 12(S)-HETE, which are metabolites of arachidonic acid generated by cytochrome P450 4A and lipoxygenase, respectively, produced on activation of cPLA 2 . The purpose of this study was to determine if Ang II-induced PLD activation in VSMCs is mediated through the ras/extracellular signal-regulating kinase (ERK) pathway by arachidonic acid metabolites that are generated consequent to cPLA 2 stimulation. Inhibitors of PLD (C 2 ceramide), phosphatidate phosphohydrolase (propranolol), and diacylglycerol lipase (RHC 80267) attenuated Ang II-induced arachidonic acid release. Ang II-induced PLD activation, as measured by [ 3 H]phosphatidylethanol production, was inhibited by C 2 ceramide but not by propranolol or RHC 80267. Ang II-induced PLD activation was decreased by the inhibitor methyl arachidonylfluorophosphate (MAFP) and the antisense oligonucleotide of cPLA 2 . Inhibitors of lipoxygenases (baicalein) and cytochrome P450 4A (ODYA) attenuated Ang II-induced PLD activation. 20-HETE and 12(S)-HETE increased PLD activity. Inhibitors of ras farnesyltransferase (FPT III and BMS-191563) and MAP kinase kinase (UO126) attenuated the increase in PLD activity elicited by 20-HETE and Ang II. PLD2 was the main isoform activated by Ang II in VSMCs. These data suggest that the CYP4A metabolite 20-HETE, which is generated from arachidonic acid after cPLA 2 activation by Ang II, stimulates the ras/MAP kinase pathway, which in turn activates PLD2 and releases further arachidonic acid for prostaglandin synthesis through the phosphatidate phosphohydrolase/diacylglycerol lipase pathway. (Ang II), an octapeptide, stimulates the migration, hypertrophy, and hyperplasia of vascular smooth muscle cells (VSMCs). 1-3 Ang II produces these biological actions by generating lipid mediators, including arachidonic acid and its metabolites, consequent to the activation of phospholipase A 2 (PLA 2 ), phospholipase C, and phospholipase D (PLD) and by producing superoxide and hydrogen peroxide. 4,5 The activation of PLA 2 releases arachidonic acid directly from phospholipids, whereas PLD catalyzes the hydrolysis of phosphatidylcholine into choline and phosphatidic acid. 6 The latter can be converted into arachidonic acid for prostaglandin synthesis by PLA 2 or sequentially by phosphatidate phosphohydrolase and diacylglycerol lipase. 7 Products generated by lipoxygenase, 12(S)-hydroxyeicosatetraenoic acid (HETE), and/or cytochrome P 450 4A (CYP4A), 20-HETE, from arachidonic acid liberated by cytostolic PLA 2 (cPLA 2 ) in response to Ang II, cause smooth muscle hyperplasia and contribute to the hypertension caused by this peptide. 8 -10 Recently, we reported that 20-HETE activates ras/mitogenactivated protein (MAP) kinase, which stimulates VSMC proli...

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Cpla 2 and Cytochrome P450 Product 20-hete Mediate Ang IImentioning

confidence: 99%

mentioning

confidence: 92%

See 1 more Smart Citation

20-Hydroxyeicosatetraenoic Acid Mediates Angiotensin II–Induced Phospholipase D Activation in Vascular Smooth Muscle Cells

et al. 2001

View full text Add to dashboard Cite

show abstract

“…PLD1 has low basal activity, requires phosphatidylinositol 4,5-bisphosphate (PIP 2 ) for its activation and is activated by protein kinase C (PKC), adenosine ribosylation factor (ARF) and Rho small G-protein family members via direct association [9][10][11][12]. PLD2 also requires PIP 2 for its enzymatic activity [13], but unlike PLD1, it can be activated by unsaturated fatty acids such as oleate [1,[14][15][16][17]. PLD2 is now recognized as the major myocardial PLD isozyme specifically localized to the SL membrane [18].…”

Section: Introductionmentioning

confidence: 99%

Expression of phospholipase D isozymes in scar and viable tissue in congestive heart failure due to myocardial infarction

Dent

Singal

Dhalla

et al. 2004

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

The phospholipase D (PLD) associated with the cardiac sarcolemmal (SL) membrane hydrolyses phosphatidylcholine to produce phosphatidic acid, an important phospholipid signaling molecule known to influence cardiac function. The present study was undertaken to examine PLD isozyme mRNA expression, protein contents and activities in congestive heart failure (CHF) subsequent to myocardial infarction (MI). MI was induced in rats by occlusion of the left anterior descending coronary artery. At 8 weeks after the surgical procedure, hemodynamic assessment revealed that these experimental rats were at a moderate stage of CHF. Semi‐quantitative reverse transcriptase‐polymerase chain reaction revealed that PLD1 and PLD2 mRNA amounts were unchanged in viable left ventricular (LV) tissue of the failing heart. Furthermore, this technique demonstrated the presence of PLD1 and PLD2 mRNA in the scar tissue. While SL PLD1 and PLD2 protein contents were elevated in the viable LV tissue of the failing heart, SL PLD1 activity was significantly decreased, whereas SL PLD2 activity was significantly increased. On the other hand, although PLD1 protein was undetectable, PLD2 protein and activity were detected in the scar tissue. Our findings suggest that differential changes in PLD isozymes may contribute to the pathophysiology of CHF and may also be involved in the processes of scar remodeling.

show abstract

“…Cardiac sarcolemmal cis-unsaturated fatty acid sensitive phospholipase D (cis-UFA phospholipase D) is modulated by iPLA 2 activity via intramembrane release of cis-UFA [12,25]. As phospholipase D-derived phosphatidic acid influences intracellular Ca 2+ concentration and contractile performance [26], changes in iPLA 2 activity may contribute to abnormal function of the failing heart.…”

Section: Linkage To Other Mechanisms Of Anthracycline Cardiotoxicitymentioning

confidence: 99%

Anthracycline-induced phospholipase A2 inhibition

2007

View full text Add to dashboard Cite

The purpose of this essay is to overview our findings that membrane-associated calciumindependent phospholipase A 2 is markedly inhibited by low, clinically relevant concentrations of anthracyclines. Our studies suggest that due to the essential role of this enzyme in membrane homeostasis, its inhibition can be one of the early culprits leading to anthracycline-induced cardiac dysfunction. The clinical importance and potential pharmaceutical use of this new phenomenon await further studies.

show abstract

Phospholipase A2-Mediated Activation of Phospholipase D in Rat Heart Sarcolemma

Cited by 33 publications

References 20 publications

20-Hydroxyeicosatetraenoic Acid Mediates Angiotensin II–Induced Phospholipase D Activation in Vascular Smooth Muscle Cells

20-Hydroxyeicosatetraenoic Acid Mediates Angiotensin II–Induced Phospholipase D Activation in Vascular Smooth Muscle Cells

Expression of phospholipase D isozymes in scar and viable tissue in congestive heart failure due to myocardial infarction

Anthracycline-induced phospholipase A2 inhibition

Contact Info

Product

Resources

About