Insulin-like Growth Factor-1 Induces an Inositol 1,4,5-Trisphosphate-dependent Increase in Nuclear and Cytosolic Calcium in Cultured Rat Cardiac Myocytes

Ibarra, Carmen; Estrada, Manuel; Carrasco, Loreto; Chiong, Mario; Liberona, José Luis; Cárdenas, César; Díaz‐Araya, Guillermo; Jaimovich, Enrique; Lavandero, Sergio

doi:10.1074/jbc.m311604200

Cited by 71 publications

(84 citation statements)

References 68 publications

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“…These same agonists also promote hypertrophic growth of neonatal cardiac myocytes [104,105]. Studies using immunostaining, Western blotting and analysis of mRNA have suggested that IP 3 R types 1, 2 and 3 are expressed in neonatal cells [102,103,106].…”

Section: Ip 3 Signaling In Cardiac Developmentmentioning

confidence: 99%

“…Almost all studies that examined either the distribution of IP 3 Rs, or the spatial pattern of IP 3 -evoked Ca 2+ signals, have reported that the channels are largely expressed in close proximity to the nucleus in neonatal cells [102,103,[106][107][108]. This is unlike RyRs, which have a more widespread expression pattern in neonatal cells [102].…”

Section: Ip 3 Signaling In Cardiac Developmentmentioning

confidence: 99%

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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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Section: Ip 3 Signaling In Cardiac Developmentmentioning

confidence: 99%

Section: Ip 3 Signaling In Cardiac Developmentmentioning

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

View full text Add to dashboard Cite

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“…Primary cultures of cardiomyocytes were cultured from hearts of 1-to 3-day-old Sprague-Dawley rats seeded on gelatin-coated coverslips and starved in serum-free medium 24 h prior to the experiment. The protocol produces cultures of cardiac myocytes that are at least 95% pure (30).…”

Section: Methodsmentioning

confidence: 99%

“…Cardiac myocytes were prepared as described in ref. 30. Primary cultures of cardiomyocytes were cultured from hearts of 1-to 3-day-old Sprague-Dawley rats seeded on gelatin-coated coverslips and starved in serum-free medium 24 h prior to the experiment.…”

Section: Methodsmentioning

confidence: 99%

Gain-of-function/Noonan syndrome SHP-2/ Ptpn11 mutants enhance calcium oscillations and impair NFAT signaling

Uhlén

Burch

Zito

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Gain-of-function mutations in SHP-2͞PTPN11 cause Noonan syndrome, a human developmental disorder. Noonan syndrome is characterized by proportionate short stature, facial dysmorphia, increased risk of leukemia, and congenital heart defects in Ϸ50% of cases. Congenital heart abnormalities are common in Noonan syndrome, but the signaling pathway(s) linking gain-of-function SHP-2 mutants to heart disease is unclear. Diverse cell types coordinate cardiac morphogenesis, which is regulated by calcium (Ca 2؉ ) and the nuclear factor of activated T-cells (NFAT). It has been shown that the frequency of Ca 2؉ oscillations regulates NFAT activity. Here, we show that in fibroblasts, Ca 2؉ oscillations in response to FGF-2 require the phosphatase activity of SHP-2. Conversely, gain-of-function mutants of SHP-2 enhanced FGF-2-mediated Ca 2؉ oscillations in fibroblasts and spontaneous Ca 2؉ oscillations in cardiomyocytes. The enhanced frequency of cardiomyocyte Ca 2؉ oscillations induced by a gain-of-function SHP-2 mutant correlated with reduced nuclear translocation and transcriptional activity of NFAT. These data imply that gain-of-function SHP-2 mutants disrupt the Ca 2؉ oscillatory control of NFAT, suggesting a potential mechanism for congenital heart defects in Noonan syndrome.calcium signaling ͉ cardiomyocytes ͉ FGF ͉ receptor tyrosine kinase signaling ͉ tyrosine phosphatases T he ubiquitously expressed src homology 2 (SH2)-containing protein tyrosine phosphatase (PTP), SHP-2 (PTPN11), regulates numerous intracellular signaling cascades that control cell proliferation, differentiation, cell survival, migration, adhesion, and apoptosis (1). SHP-2 contains two NH 2 terminus SH2 domains, a PTP domain, and a COOH terminus containing two tyrosyl phosphorylation sites (1). It is now well established that SHP-2 is required for activation of the extracellular-regulated kinases (ERKs) 1 and 2 in response to the activation of receptor tyrosine kinase (RTK) and cytokine receptors (1). The SH2 domains of SHP-2 mediate not only binding to RTKs but also scaffold proteins such as Gab-1, IRS-1, and FRS-2 (1). In virtually all cases, stimulation of SHP-2 catalysis is required for downstream signaling. The SH2 domains of SHP-2 also regulate its activation. Engagement of the NH 2 SH2 domain of SHP-2 with its cognate phosphotyrosyl protein results in its activation. The mechanism of this activation involves displacement of the NH 2 SH2 domain from the PTP domain which in the basal (unbound SH2 domain) state occludes the PTP active site. Upon NH 2 SH2 domain binding, a conformational relief of this inhibitory state is achieved and the phosphatase becomes active. Insights from the crystallographic structure of SHP-2 (2) resulted in the generation of engineered mutations at residues critical for the maintenance of the basal inactivated state of SHP-2. These mutations, within the NH 2

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“…Cardiomyocytes were isolated from Pkd2 ϩ/ϩ and Pkd2 Ϫ/Ϫ embryos at embryonic day 17.5 and cultured by using a method as described with a few modifications (46). Ca 2ϩ imaging experiments were performed by using fluo-4-loaded cells, which then were observed with a Zeiss LSM510 confocal microscope (47).…”

Section: Isolation Of Mouse Cardiomyocytes and Ca 2؉ Imaging Experimementioning

confidence: 99%

Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2

Anyatonwu¹,

Estrada²,

Tian³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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150

141

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Mutations in polycystin-2 (PC2) cause autosomal dominant polycystic kidney disease. A function for PC2 in the heart has not been described. Here, we show that PC2 coimmunoprecipitates with the cardiac ryanodine receptor (RyR2) from mouse heart. Biochemical assays showed that the N terminus of PC2 binds the RyR2, whereas the C terminus only binds to RyR2 in its open state. Lipid bilayer electrophysiological experiments indicated that the C terminus of PC2 functionally inhibited RyR2 channel activity in the presence of calcium (Ca 2؉ ). Pkd2 ؊/؊ cardiomyocytes had a higher frequency of spontaneous Ca 2؉ oscillations, reduced Ca 2؉ release from the sarcoplasmic reticulum stores, and reduced Ca 2؉ content compared with Pkd2 ؉/؉ cardiomyocytes. In the presence of caffeine, Pkd2 ؊/؊ cardiomyocytes exhibited decreased peak fluorescence, a slower rate of rise, and a longer duration of Ca 2؉ transients compared with Pkd2 ؉/؉ . These data suggest that PC2 is important for regulation of RyR2 function and that loss of this regulation of RyR2, as occurs when PC2 is mutated, results in altered Ca 2؉ signaling in the heart. intracellular calcium channel ͉ polycystic kidney disease ͉ lipid bilayer ͉ calcium imaging ͉ cardiac cells

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Insulin-like Growth Factor-1 Induces an Inositol 1,4,5-Trisphosphate-dependent Increase in Nuclear and Cytosolic Calcium in Cultured Rat Cardiac Myocytes

Abstract: In the heart, insulin-like growth factor-1 (IGF-1) is a pro-hypertrophic and anti-apoptotic peptide. In cultured rat cardiomyocytes, IGF-1 induced a fast and transient increase in Ca

Cited by 71 publications

References 68 publications

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

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

Gain-of-function/Noonan syndrome SHP-2/ Ptpn11 mutants enhance calcium oscillations and impair NFAT signaling

Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2

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