Changes in sarcolemmal PLC isoenzymes in postinfarct congestive heart failure: partial correction by imidapril

Tappia, Paramjit S.; Liu, Song-Yan; Shatadal, Shalini; Takeda, Nobuakira; Dhalla, Naranjan S.; Panagia, Vincenzo

doi:10.1152/ajpheart.1999.277.1.h40

Cited by 40 publications

(43 citation statements)

References 52 publications

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“…In this regard, and relevant to cardiac pathophysiology, it is noteworthy that up-regulation of the G␣ q protein has been reported in the border zones of the myocardium after infarct (40), a paradigm in which there is also enhanced release of G␣ q -coupled receptor agonists (41). In addition, increased expression of PLC␤ has been reported to occur in a model of chronic heart failure (42). Furthermore, in two models of heart failure (the cardiomyopathic hamster and post-myocardial infarct), there is evidence for decreased PIP 2 mass and decreased expression of phosphatidylinositol 4-phosphate 5-ki- Fig.…”

Section: Discussionmentioning

confidence: 95%

“…*, p Ͻ 0.05 compared with nontransgenic peripartum. nase, the enzyme required to replete stores of PIP 2 (42,43). We show here that in another model of heart failure, the peripartal cardiomyopathy seen in transgenic mice expressing G␣ q , both PIP 2 levels and Akt phosphorylation are decreased compared with nontransgenic littermate controls.…”

Section: Discussionmentioning

confidence: 99%

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Akt-mediated Cardiomyocyte Survival Pathways Are Compromised by Gαq-induced Phosphoinositide 4,5-Bisphosphate Depletion

Howes¹,

Arthur²,

Zhang³

et al. 2003

Journal of Biological Chemistry

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Expression of the wild type ␣ subunit of G q (G q WT) in cardiomyocytes induces hypertrophy, whereas a constitutively active G␣ q subunit (G q Q209L) induces apoptosis. Akt phosphorylation increases with G q WT expression but is markedly attenuated in cardiomyocytes expressing G q Q209L or in those expressing G q WT and treated with agonist. A membrane-targeted Akt rescues G q Q209L-expressing cardiomyocytes from apoptotic cell death. In contrast, leukemia inhibitory factor fails to activate Akt or promote cell survival in these cells. Association of Akt and PDK-1 with the membrane is also diminished in G q Q209L-expressing cardiomyocytes. Phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ), the primary regulator of Akt, increases significantly in G q WTexpressing cells but not in cardiomyocytes expressing G q Q209L. Levels of phosphatidylinositol 4,5-bisphosphate (PIP 2 ), the immediate precursor of PIP 3 , are also markedly lower in G q Q209L-expressing compared to control cells. Expression of a G q Q209L mutant that has diminished capacity to activate phospholipase C does not decrease PIP 2 or Akt or induce apoptosis. In transgenic mice with cardiac G␣ q overexpression, heart failure and increased cardiomyocyte apoptosis develop during the peripartal period. Akt phosphorylation and PIP 2 levels decrease concomitantly. Our findings suggest that an Akt-mediated cell survival pathway is compromised by the diminished availability of PIP 2 elicited by pathological levels of G q activity.G␣ q signaling plays a key role in the hypertrophic growth of cardiomyocytes. Hormones that act through receptors coupled to the heterotrimeric protein G q (e.g. norepinephrine, PGF 2␣ , 1 endothelin, and angiotensin II) induce cardiomyocyte hypertrophy in vitro (1). Further evidence for a physiological role of G␣ q activation is that blocking G q signaling in vivo prevents pressure-overload hypertrophy (2, 3). Hypertrophy can transition to heart failure under conditions of enhanced G␣ q signaling induced by overexpression of G q -coupled receptors, of phospholipase C-␤ (PLC), of constitutively active G␣ q , or of wild type G␣ q in combination with stress (4 -11). Thus studies in isolated cardiomyocytes and in transgenic animals have led to the conclusion that although G␣ q signaling is critical for cardiac hypertrophy, prolonged or marked enhancement of G q activity is deleterious to the heart.Our laboratory has characterized a model of in vitro cardiomyocyte hypertrophy and apoptosis by expressing the ␣ subunit of G q (8). When the wild type ␣ subunit (G q WT) is expressed by adenoviral infection, neonatal rat ventricular myocytes (NRVMs) undergo hypertrophy (8). In contrast, when the constitutively active ␣ subunit (G q Q209L) is expressed, or G q WTexpressing cardiomyocytes are treated with G q -coupled receptor agonists, the NRVMs undergo apoptosis (8,12). Varying the amount of G␣ q signaling in myocytes therefore results in distinct cellular phenotypes. Although modest levels of signaling induce hypertrophy, at higher levels su...

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Akt-mediated Cardiomyocyte Survival Pathways Are Compromised by Gαq-induced Phosphoinositide 4,5-Bisphosphate Depletion

Howes¹,

Arthur²,

Zhang³

et al. 2003

Journal of Biological Chemistry

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“…In human heart failure, expression of α 1 -adrenergic receptors is unchanged (but their relative expression is increased due to a large downregulation of the predominating β 1 -adrenergic receptors) [196], AT 1 receptors are downregulated (presumably due to increased angiotensin II levels [197]) and ET A receptors are upregulated [198,199]. In animal models of heart failure, changes in phosphoinositide metabolism occur, including alterations in the abundance, expression and/or activity of PIP 2 , PI-4 kinase, PIP-5 kinase, PLC isoforms and inositol phosphates [200,201]. Expression of IP 3 Rs is increased in both human and animal heart failure, whereas RyR levels are reduced, indicating a shift toward more IP 3 R-mediated Ca 2+ release in the failing heart [19,202].…”

Section: Hypertrophy and Heart Failurementioning

confidence: 99%

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

Kockskämper

Zima

Roderick

et al. 2008

Journal of Molecular and Cellular Cardiology

173

149

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Inositol 1,4,5-trisphosphate (IP 3 ) is a ubiquitous intracellular messenger regulating diverse functions in almost all mammalian cell types. It is generated by membrane receptors that couple to phospholipase C (PLC), an enzyme which liberates IP 3 from phosphatidylinositol 4,5-bisphosphate (PIP 2 ). The major action of IP 3 , which is hydrophilic and thus translocates from the membrane into the cytoplasm, is to induce Ca 2+ release from endogenous stores through IP 3 receptors (IP 3 Rs). Cardiac excitation-contraction coupling relies largely on ryanodine receptor (RyR)-induced Ca 2+ release from the sarcoplasmic reticulum. Myocytes express a significantly larger number of RyRs compared to IP 3 Rs (∼100:1), and furthermore they experience substantial fluxes of Ca 2+ with each heartbeat. Therefore, the role of IP 3 and IP 3 -mediated Ca 2+ signaling in cardiac myocytes has long been enigmatic. Recent evidence, however, indicates that despite their paucity cardiac IP 3 Rs may play crucial roles in regulating diverse cardiac functions. Strategic localization of IP 3 Rs in cytoplasmic compartments and the nucleus enables them to participate in subsarcolemmal, bulk cytoplasmic and nuclear Ca 2+ signaling in embryonic stem cell-derived and neonatal cardiomyocytes, and in adult cardiac myocytes from the atria and ventricles. Intriguingly, expression of both IP 3 Rs and membrane receptors that couple to PLC/IP 3 signaling is altered in cardiac disease such as atrial fibrillation or heart failure, suggesting the involvement of IP 3 signaling in the pathology of these diseases. Thus, IP 3 exerts important physiological and pathological functions in the heart, ranging from the regulation of pacemaking, excitation-contraction and excitation-transcription coupling to the initiation and/or progression of arrhythmias, hypertrophy and heart failure. KeywordsInositol 1,4,5-trisphosphate; Cardiac myocyte; Calcium; Inotropy; Arrhythmias; Nucleus; Hypertrophy © 2008 Elsevier Inc. All rights reserved. * Corresponding author. E-mail address: jens.kockskaemper@meduni-graz.at (J. Kockskämper).. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript The discovery of IP 3A quarter of a century ago it was shown that D-myo inositol 1,4,5-trisphosphate (IP 3 ) releases Ca 2+ from a non-mitochondrial internal Ca 2+ store [1]. Since this hallmark discovery, IP 3 has emerged as a ubiquitous intracellular messenger, releasing Ca 2+ from stores through activation of IP 3 receptors (IP 3 Rs) in almost all eukaryotic cells. The major IP 3 -sensitive intracellular Ca 2+ store is the endoplasmic reticulum. However, IP 3 has also been shown to release Ca 2+ stored in other compartments, such as the Golgi and the nuclear envelope [2]. In addition, IP 3 Rs are present on the plasma membrane of some cell types, where they can gate Ca 2+ influx [3]. A crucial role for IP 3 -dependent Ca 2+ release has been demonstrated in many mammalian cell types, ranging from tiny platelets, where it initiates blood clottin...

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“…MI was induced in male Sprague-Dawley (SD) rats (weighing 175-200 g) by surgical occlusion of the left anterior descending coronary artery [21][22][23][24]. The animals were anesthetized with 5% isoflurane in oxygen at a flow rate of 2 l/min.…”

Section: Experimental Modelmentioning

confidence: 99%

“…For this purpose, we employed viable left ventricular (LV) and scar tissues taken from rats 8 weeks after ligation of the left anterior descending coronary artery when the animals were at moderate stage of CHF [21][22][23].…”

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

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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.

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Changes in sarcolemmal PLC isoenzymes in postinfarct congestive heart failure: partial correction by imidapril

Cited by 40 publications

References 52 publications

Akt-mediated Cardiomyocyte Survival Pathways Are Compromised by Gαq-induced Phosphoinositide 4,5-Bisphosphate Depletion

Akt-mediated Cardiomyocyte Survival Pathways Are Compromised by Gαq-induced Phosphoinositide 4,5-Bisphosphate Depletion

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

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

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