Phospholipase C may be involved in norepinephrine-induced cardiac hypertrophy

Singal, Tushi; Dhalla, Naranjan S.; Tappia, Paramjit S.

doi:10.1016/j.bbrc.2004.06.052

Cited by 33 publications

(25 citation statements)

References 29 publications

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“…A role of PLC in norepinephrine-induced cardiomyocyte hypertrophy has been shown (42). In the present study, we also report that U73122, an inhibitor of PLC, significantly attenuated the enhanced protein synthesis in VSMC from 16-wk-old SHR and provide the first evidence that PLC activation may be directly involved in VSMC hypertrophy.…”

Section: Discussionsupporting

confidence: 82%

Enhanced expression of G_qα and PLC-β1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1

Atef

Anand‐Srivastava

2014

American Journal of Physiology-Cell Physiology

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Atef ME, Anand-Srivastava MB. Enhanced expression of Gq␣ and PLC-␤1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1. Am J Physiol Cell Physiol 307: C97-C106, 2014. First published April 24, 2014 doi:10.1152 doi:10. /ajpcell.00337.2013 Gq␣ signaling has been shown to contribute to cardiac hypertrophy. In addition, angiotensin II (ANG II) was shown to induce vascular smooth muscle cell (VSMC) hypertrophy through Gq␣ signaling; however, the studies on the role of Gq␣ and PLC-␤1 proteins in VSMC hypertrophy in animal model are lacking. The present study was therefore undertaken to examine the role of Gq␣/PLC-␤1 proteins and the signaling pathways in VSMC hypertrophy using spontaneously hypertensive rats (SHR). VSMC from 16-wk-old SHR and not from 12-wk-old SHR exhibited enhanced levels of Gq␣/PLC-␤1 proteins compared with age-matched Wistar-Kyoto (WKY) rats as determined by Western blotting. However, protein synthesis as determined by [ 3 H]leucine incorporation was significantly enhanced in VSMC from both 12-and 16-wk-old SHR compared with VSMC from age-matched WKY rats. Furthermore, the knockdown of Gq␣/ PLC-␤1 in VSMC from 16-wk-old SHR by antisense and small interfering RNA resulted in attenuation of protein synthesis. In addition, the enhanced expression of Gq␣/PLC-␤1 proteins, enhanced phosphorylation of ERK1/2, and enhanced protein synthesis in VSMC from SHR were attenuated by the ANG II AT1 and endothelin-1 (ET-1) ETA receptor antagonists losartan and BQ123, respectively, but not by the ETB receptor antagonist BQ788. In addition, PD98059 decreased the enhanced expression of Gq␣/PLC-␤1 and protein synthesis in VSMC from SHR. These results suggest that the enhanced levels of endogenous ANG II and ET-1 through the activation of AT1 and ETA receptors, respectively, and MAP kinase signaling, enhanced the expression of Gq␣/PLC-␤1 proteins in VSMC from 16-wk-old SHR and result in VSMC hypertrophy.Gq␣ protein; PLC-␤1 protein; SHR; VSMC; hypertrophy THE HETEROTRIMERIC GUANINE nucleotide regulatory protein (G protein), composed of three subunits (␣, ␤, and ␥), plays a crucial role in the regulation of cardiovascular functions through the activation of several signal transduction systems including adenylyl cyclase and phosphatidyl inositide system (39). Based on ␣-subunit sequence similarity, G␣ proteins are divided into four families G s , G i/o , G q/11 , and G 12/13 . G s and G i proteins regulate the activity of adenylyl cyclase whereas the activation of G q ␣ by a G protein-coupled receptor (GPCR) stimulates phospholipase C-␤ (PLC-␤), which hydrolyzes inositol biphosphate (PIP2) and produces inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] (IP 3 ) and diacylglycerol (DAG) (23) and activates protein kinase C (PKC) (7,43).Alterations in the levels of G q ␣ protein and associated signaling pathways appear to contribute to the impaired cellular functions in several pathological states including diabetes, hyperglycemia, and cardiac hypertrophy (1, 12...

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Section: Discussionsupporting

confidence: 82%

Enhanced expression of G_qα and PLC-β1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1

Atef

Anand‐Srivastava

2014

American Journal of Physiology-Cell Physiology

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“…Its role in the regulation of protein translation has not been studied in depth. U73122, an inhibitor of PLC, has been shown to abolish cardiac myocyte hypertrophy induced by norepineph- rine (24), although it appears to be not required in angiotensin II induction of protein synthesis in cardiac fibroblasts (25). Thus, the involvement of PLC␥ in protein synthesis appears to be cell-and agonist-specific.…”

Section: Discussionmentioning

confidence: 99%

Phospholipase Cγ-Erk Axis in Vascular Endothelial Growth Factor-induced Eukaryotic Initiation Factor 4E Phosphorylation and Protein Synthesis in Renal Epithelial Cells

Mariappan¹,

Duraisamy²,

Natarajan³

et al. 2005

Journal of Biological Chemistry

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“…It is well known that stimulation of myocytes with hormones that activate IP 3 production, e.g. ET-1, can promote hypertrophy [150][151][152][153][154]. What is not fully understood, however, is how such hormones can affect subtle changes in Ca 2+ -dependent gene transcription inside cells that experience periodic surges of Ca 2+ during excitation-contraction coupling [155].…”

Section: Ip 3 Signaling In Ventricular Myocytesmentioning

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

172

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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Phospholipase C may be involved in norepinephrine-induced cardiac hypertrophy

Cited by 33 publications

References 29 publications

Enhanced expression of G_qα and PLC-β1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1

Enhanced expression of G_qα and PLC-β1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1

Phospholipase Cγ-Erk Axis in Vascular Endothelial Growth Factor-induced Eukaryotic Initiation Factor 4E Phosphorylation and Protein Synthesis in Renal Epithelial Cells

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

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Phospholipase C may be involved in norepinephrine-induced cardiac hypertrophy

Cited by 33 publications

References 29 publications

Enhanced expression of Gqα and PLC-β1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1

Enhanced expression of Gqα and PLC-β1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1

Phospholipase Cγ-Erk Axis in Vascular Endothelial Growth Factor-induced Eukaryotic Initiation Factor 4E Phosphorylation and Protein Synthesis in Renal Epithelial Cells

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

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Enhanced expression of G_qα and PLC-β1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1

Enhanced expression of G_qα and PLC-β1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1