122 results on '"Catalucci, Daniele"'
Search Results
102. MiR-133a regulates collagen 1A1: Potential role of miR-133a in myocardial fibrosis in angiotensin II-dependent hypertension.
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Castoldi, Giovanna, di Gioia, Cira R.T., Bombardi, Camila, Catalucci, Daniele, Corradi, Barbara, Gualazzi, Maria Giovanna, Leopizzi, Martina, Mancini, Massimiliano, Zerbini, Gianpaolo, Condorelli, Gianluigi, and Stella, Andrea
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MICRORNA ,COLLAGEN ,FIBROSIS ,ANGIOTENSIN II ,HYPERTENSION ,CARDIOMYOPATHIES ,CARDIAC hypertrophy ,LABORATORY rats - Abstract
MicroRNAs play an important role in myocardial diseases. MiR-133a regulates cardiac hypertrophy, while miR-29b is involved in cardiac fibrosis. The aim of this study was to evaluate whether miR-133a and miR-29b play a role in myocardial fibrosis caused by Angiotensin II (Ang II)-dependent hypertension. Sprague-Dawley rats were treated for 4 weeks with Ang II (200 ng/kg/min) or Ang II + irbesartan (50 mg/kg/day in drinking water), or saline by osmotic minipumps. At the end of the experimental period, cardiac miR-133a and miR-29b expression was measured by real-time PCR, and myocardial fibrosis was evaluated by morphometric analysis. A computer-based prediction algorithm led to the identification of collagen 1a1 (Col1A1) as a putative target of miR-133a. A reporter plasmid bearing the 3′-untranslated regions (UTRs) of Col1A1 mRNA was constructed and luciferase assay was performed. MiR-133a suppressed the activity of luciferase when the reporter gene was linked to a 3′-UTR segment of Col1A1 ( P < 0.01). Mutation of miR-133a binding sites in the 3′-UTR of Col1A1 mRNA abolished miR-133a-mediated repression of reporter gene activity, showing that Col1A1 is a real target of miR-133a. In vivo, Ang II caused an increase in systolic blood pressure ( P < 0.0001, tail cuff) and myocardial fibrosis in presence of a decrease in miR-133a ( P < 0.01) and miR-29b ( P < 0.01), and an increase in Col1A1 expression ( P < 0.01). These effects were abolished by Ang II administration + irbesartan. These data demonstrate a relationship between miR-133a and Col1A1, suggesting that myocardial fibrosis occurring in Ang II-dependent hypertension is regulated by the down-regulation of miR-133a and miR-29b through the modulation of Col1A1 expression. J. Cell. Physiol. 227: 850-856, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
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- 2012
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103. Akt Increases Sarcoplasmic Reticulum Ca2+ Cycling by Direct Phosphorylation of Phospholamban at Thr17.
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Catalucci, Daniele, Latronico, Michael V. G., Ceci, Marcello, Rusconi, Francesca, Young, Howard S., Gallo, Paolo, Santonastasi, Marco, Bellacosa, Alfonso, Brown, Joan Heller, and Condorelli, Gianluigi
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HEART cells , *CELL physiology , *PHYSIOLOGICAL adaptation , *SARCOPLASMIC reticulum , *BIOLOGICAL assay , *PHOSPHORYLATION , *HYPERTROPHY , *LABORATORY mice - Abstract
Cardiomyocytes adapt to physical stress by increasing their size while maintaining cell function. The serine/threonine kinase Akt plays a critical role in this process of adaptation. We previously reported that transgenic overexpression of an active form of Akt (Akt-E4AI)K) in mice results in increased cardiac contractility and cell size, as well as improved sarcoplasmic reticulum (SR) Ca2+ handling. Because it is not fully elucidated, we decided to study the molecular mechanism by which Akt-E40K overexpression improves SR Ca2+ handling. To this end, SR Ca2+ uptake and the phosphorylation status of phospholamban (PLN) were evaluated in heart extracts from wild-type and Akt-E40K mice and mice harboring inducible and cardiac specffic knock-out of phosphatidylinositol-dependent kinase-1, the upstream activator of Akt. Moreover, the effect of Akt was assessed in vitro by overexpressing a mutant Akt targeted preferentially to the SR, and by biochemical assays to evaluate potential interaction with PLN. We found that when activated, Akt interacts with and phosphorylates PLN at Thr17, the Ca2+-calmodulin-dependent kinase IIδ site, whereas silencing Akt signaling, through the knock-out of phosphatidylinositol-dependent kinase-1, resulted in reduced phosphorylation of PLN at Thr17. Furthermore, overexpression of SR-targeted Akt in cardiomyocytes improved Ca2+ handling without affecting cell size. Thus, we describe here a new mechanism whereby the preferential translocation of Akt to the SR is responsible for enhancement of contractility without stimulation of hypertrophy. [ABSTRACT FROM AUTHOR]
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- 2009
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104. Interval Training Normalizes Cardiomyocyte Function, Diastolic Ca2+ Control, and SR Ca2+ Release Synchronicity in a Mouse Model of Diabetic Cardiomyopathy.
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St∅len, Tomas O., H∅ydal, Morten Andre, Kemi, Ole Johan, Catalucci, Daniele, Ceci, Marcello, Aasum, Ellen, Larsen, Terje, Rolim, Natale, Condorelli, Gianluigi, Smith, Godfrey L., and Wisl∅ff, Uhik
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MEDICAL research ,INTERVAL training ,EXCITATION (Physiology) ,CARDIAC contraction ,HEART cells ,AEROBIC exercises - Abstract
The article reports on the study of the mechanisms of excitation-contraction (EC) coupling defects in cardiomyocytes from mice with type 2 diabetes. It notes that the study aims to identify if 13 weeks of aerobic interval training could restore cardiomyocyte cycling and EC coupling. It presents the methods and results of the study wherein it concludes that aerobic interval training returned the contractile function of the diabetic cardiomyocyte.
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- 2009
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105. Akt regulates L-type Ca2+ channel activity by modulating Cavα 1 protein stability.
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Catalucci, Daniele, Deng-Hong Zhang, DeSantiago, Jaime, Aimond, Franck, Barbara, Guillaume, Chemin, Jean, Bonci, Désiré, Picht, Eckard, Rusconi, Francesca, Dalton, Nancy D., Peterson, Kirk L., Richard, Sylvain, Bers, Donald M., Brown, Joan Heller, and Condorelli, Gianluigi
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PROTEIN kinases , *INSULIN , *INSULIN-like growth factor-binding proteins , *MOLECULAR chaperones , *PHOSPHORYLATION , *MUSCLE cells - Abstract
The insulin IGF-1-PI3K-Akt signaling pathway has been suggested to improve cardiac inotropism and increase Ca2+ handling through the effects of the protein kinase Akt. However, the underlying molecular mechanisms remain largely unknown. In this study, we provide evidence for an unanticipated regulatory function of Akt controlling L-type Ca2+ channel (LTCC) protein density. The pore-forming channel subunit Cavα1 contains highly conserved PEST sequences (signals for rapid protein degradation), and in-frame deletion of these PEST sequences results in increased Ca[sub v]α1 protein levels. Our findings show that Akt-dependent phosphorylation of Cavβ2, the LTCC chaperone for Cavα1, antagonizes Cavα1 protein degradation by preventing Cavα1 PEST sequence recognition, leading to increased LTCC density and the consequent modulation of Ca2+ channel function. This novel mechanism by which Akt modulates LTCC stability could profoundly influence cardiac myocyte Ca2+ entry, Ca2+ handling, and contractility. [ABSTRACT FROM AUTHOR]
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- 2009
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106. Calcium Phosphate Nanoparticle Precipitation by a Continuous Flow Process: A Design of an Experiment Approach.
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Degli Esposti, Lorenzo, Dotti, Alessandro, Adamiano, Alessio, Fabbi, Claudia, Quarta, Eride, Colombo, Paolo, Catalucci, Daniele, De Luca, Claudio, and Iafisco, Michele
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EXPERIMENTAL design ,CONTINUOUS processing ,NANOPARTICLES ,ENGINEERING laboratories ,CALCIUM phosphate ,SONICATION - Abstract
Calcium phosphate nanoparticles (CaP NPs) are an efficient class of nanomaterials mainly used for biomedical applications but also very promising in other sectors such as cosmetics, catalysis, water remediation, and agriculture. Unfortunately, as in the case of other nanomaterials, their wide application is hindered by the difficulty to control size, morphology, purity and degree of particle aggregation in the translation from laboratory to industrial scale production that is usually carried out in batch or semi-batch systems. In this regard, the use of continuous flow synthesis can help to solve this problem, providing more homogenous reaction conditions and highly reproducible synthesis. In this paper, we have studied with a design of experiment approach the precipitation of citrate functionalized CaP NPs aided by sonication using a continuous flow wet chemical precipitation, and the effect of some of the most relevant process factors (i.e., reactant flow rate, sonication amplitude, and maturation time) on the physico-chemical properties of the NPs were evaluated. From the statistical data analysis, we have found that CaP NP dimensions are influenced by the reactor flow rate, while the crystalline domain dimensions and product purity are influenced by the maturation process. This work provides a deeper understanding of the relationships between reaction process factors and CaP NP properties, and is a relevant contribution for the scale-up production of CaP NPs for nanomedical or other applications. [ABSTRACT FROM AUTHOR]
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- 2020
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107. The role of mitochondrial dynamics in cardiovascular diseases.
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Forte, Maurizio, Schirone, Leonardo, Ameri, Pietro, Basso, Cristina, Catalucci, Daniele, Modica, Jessica, Chimenti, Cristina, Crotti, Lia, Frati, Giacomo, Rubattu, Speranza, Schiattarella, Gabriele Giacomo, Torella, Daniele, Perrino, Cinzia, Indolfi, Ciro, Sciarretta, Sebastiano, Italian Society of Cardiology (SIC) Working group on Cellular and Molecular Biology of the Heart, and Italian Society of Cardiology Working group on Cellular and Molecular Biology of the Heart
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STROKE ,MYOCARDIUM ,CARDIOVASCULAR diseases ,MITOCHONDRIA ,CEREBRAL ischemia - Abstract
The process of mitochondrial dynamics is emerging as a core player in cardiovascular homeostasis. This process refers to the co-ordinated cycles of biogenesis, fusion, fission and degradation to which mitochondria constantly undergo to maintain their integrity, distribution and size. These mechanisms represent an early response to mitochondrial stress, confining organelle portions that are irreversibly damaged and preserving mitochondrial function. Accumulating evidence demonstrates that impairment in mitochondrial dynamics leads to myocardial damage and cardiac disease progression in a variety of disease models, including pressure overload, ischaemia/reperfusion and metabolic disturbance. These findings suggest that modulation of mitochondrial dynamics may be considered as a valid therapeutic strategy in cardiovascular diseases. In this review, we discuss the current evidence about the role of mitochondrial dynamics in cardiac pathophysiology, with a particular focus on the mechanisms underlying the development of cardiac hypertrophy and heart failure, metabolic and genetic cardiomyopathies, ischaemia/reperfusion injury, atherosclerosis and ischaemic stroke. LINKED ARTICLES: This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc. [ABSTRACT FROM AUTHOR]
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- 2020
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108. Figures S1 - S4 and Table S1 from A combined low-frequency electromagnetic and fluidic stimulation for a controlled drug release from superparamagnetic calcium phosphate nanoparticles: potential application for cardiovascular diseases
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Marrella, Alessandra, Iafisco, Michele, Adamiano, Alessio, Rossi, Stefano, Aiello, Maurizio, Barandalla-Sobrados, Maria, Carullo, Pierluigi, Miragoli, Michele, Tampieri, Anna, Scaglione, Silvia, and Catalucci, Daniele
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3. Good health - Abstract
Figure S1: Transmission Electron Microscopy (TEM) images of FeHAs (a, b) at two different magnifications and HAs (c); Figure S2: Hydrodynamic diameter distributions of FeHA and HA in HEPES buffer 0.1 M, pH 7.4.; Table S1: Technical data of each component of the MEBD; Figure S3: Adsorption kinetics of IBU on (▪) FeHAs and (▫) HAs.; Figure S4: Adsorption isotherms of IBU on (▪) FeHAs and (▫) HAs. Separate points are the experimental data; dotted lines indicate Sips fits of isotherm data.
109. Figures S1 - S4 and Table S1 from A combined low-frequency electromagnetic and fluidic stimulation for a controlled drug release from superparamagnetic calcium phosphate nanoparticles: potential application for cardiovascular diseases
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Marrella, Alessandra, Iafisco, Michele, Adamiano, Alessio, Rossi, Stefano, Aiello, Maurizio, Barandalla-Sobrados, Maria, Carullo, Pierluigi, Miragoli, Michele, Tampieri, Anna, Scaglione, Silvia, and Catalucci, Daniele
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3. Good health - Abstract
Figure S1: Transmission Electron Microscopy (TEM) images of FeHAs (a, b) at two different magnifications and HAs (c); Figure S2: Hydrodynamic diameter distributions of FeHA and HA in HEPES buffer 0.1 M, pH 7.4.; Table S1: Technical data of each component of the MEBD; Figure S3: Adsorption kinetics of IBU on (▪) FeHAs and (▫) HAs.; Figure S4: Adsorption isotherms of IBU on (▪) FeHAs and (▫) HAs. Separate points are the experimental data; dotted lines indicate Sips fits of isotherm data.
110. Figures S1 - S4 and Table S1 from A combined low-frequency electromagnetic and fluidic stimulation for a controlled drug release from superparamagnetic calcium phosphate nanoparticles: potential application for cardiovascular diseases
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Marrella, Alessandra, Iafisco, Michele, Adamiano, Alessio, Rossi, Stefano, Aiello, Maurizio, Barandalla-Sobrados, Maria, Carullo, Pierluigi, Miragoli, Michele, Tampieri, Anna, Scaglione, Silvia, and Catalucci, Daniele
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3. Good health - Abstract
Figure S1: Transmission Electron Microscopy (TEM) images of FeHAs (a, b) at two different magnifications and HAs (c); Figure S2: Hydrodynamic diameter distributions of FeHA and HA in HEPES buffer 0.1 M, pH 7.4.; Table S1: Technical data of each component of the MEBD; Figure S3: Adsorption kinetics of IBU on (▪) FeHAs and (▫) HAs.; Figure S4: Adsorption isotherms of IBU on (▪) FeHAs and (▫) HAs. Separate points are the experimental data; dotted lines indicate Sips fits of isotherm data.
111. Human Stem Cells for Heart Failure Treatment Ready for Prime Time?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology
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Condorelli, Gianluigi and Catalucci, Daniele
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112. Human Stem Cells for Heart Failure Treatment: Ready for Prime Time? ⁎ [⁎] Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
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Condorelli, Gianluigi and Catalucci, Daniele
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- 2007
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113. Abstract 360.
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Castaldi, Alessandra, Zaglia, Tania, Di Mauro, Vittoria, Carullo, Pierluigi, Viggiani, Giacomo, Borile, Giulia, Di Stefano, Barbara, Schiattarella, Gabriele Giacomo, Gualazzi, Maria Giovanna, Elia, Leonardo, Stirparo, Giuliano Giuseppe, Pironti, Gianluigi, Kunderfranco, Paolo, Colorito, Maria Luisa, Esposito, Giovanni, Bang, Marie-Louise, Mongillo, Marco, Condorelli, Gianluigi, and Catalucci, Daniele
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- 2014
114. Abstract 182.
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Rusconi, Francesca, Miragoli, Michele, Di Pasquale, Elisa, Rocchetti, Marcella, Ceriotti, Paola, Carullo, Pierluigi, Caprari, Silvia, Viggiani, Giacomo, Cazade, Magali, Chemin, Jean, Bang, Marie-Louise, Polticelli, Fabio, Zaza, Antonio, Condorelli, Gianluigi, and Catalucci, Daniele
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- 2014
115. Mitochondrial a Kinase Anchor Proteins in Cardiovascular Health and Disease: A Review Article on Behalf of the Working Group on Cellular and Molecular Biology of the Heart of the Italian Society of Cardiology
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Roberta Paolillo, Stefania D’Apice, Gabriele Giacomo Schiattarella, Pietro Ameri, Domenica Borzacchiello, Daniele Catalucci, Cristina Chimenti, Lia Crotti, Sebastiano Sciarretta, Daniele Torella, Antonio Feliciello, Cinzia Perrino, Paolillo, Roberta, D'Apice, Stefania, Schiattarella, Gabriele Giacomo, Ameri, Pietro, Borzacchiello, Domenica, Catalucci, Daniele, Chimenti, Cristina, Crotti, Lia, Sciarretta, Sebastiano, Torella, Daniele, Feliciello, Antonio, Perrino, Cinzia, Paolillo, R, D'Apice, S, Schiattarella, G, Ameri, P, Borzacchiello, D, Catalucci, D, Chimenti, C, Crotti, L, Sciarretta, S, Torella, D, Feliciello, A, and Perrino, C
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AKAP1 ,AKAPs ,ROS ,cAMP ,mitochondria ,protein kinase A ,Organic Chemistry ,Cardiology ,A Kinase Anchor Proteins ,Heart ,General Medicine ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,AKAP ,Cyclic AMP ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
Second messenger cyclic adenosine monophosphate (cAMP) has been found to regulate multiple mitochondrial functions, including respiration, dynamics, reactive oxygen species production, cell survival and death through the activation of cAMP-dependent protein kinase A (PKA) and other effectors. Several members of the large family of A kinase anchor proteins (AKAPs) have been previously shown to locally amplify cAMP/PKA signaling to mitochondria, promoting the assembly of signalosomes, regulating multiple cardiac functions under both physiological and pathological conditions. In this review, we will discuss roles and regulation of major mitochondria-targeted AKAPs, along with opportunities and challenges to modulate their functions for translational purposes in the cardiovascular system.
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- 2022
116. Mutual antagonism between IP3RII and miRNA-133a regulates calcium signals and cardiac hypertrophy.
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Drawnel, Faye M., Wachten, Dagmar, Molkentin, Jeffery D., Maillet, Marjorie, Aronsen, Jan Magnus, Swift, Fredrik, Sjaastad, Ivar, Ning Liu, Catalucci, Daniele, Mikoshiba, Katsuhiko, Hisatsune, Chihiro, Okkenhaug, Hanneke, Andrews, Simon R., Bootman, Martin D., and Roderick, H. Llewelyn
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CARDIAC hypertrophy , *INOSITOL trisphosphate receptors , *CALCIUM channels , *MYOCARDIUM , *ARRHYTHMIA - Abstract
Inositol 1,4,5'-triphosphate receptor II (IP3RII) calcium channel expression is increased in both hypertrophic failing human myocardium and experimentally induced models of the disease. The ectopic calcium released from these receptors induces pro-hypertrophic gene expression and may promote arrhythmias. Here, we show that IP3RII expression was constitutively restrained by the muscle-specific miRNA, miR-133a. During the hypertrophic response to pressure overload or neurohormonal stimuli, miR-133a down-regulation permitted IP3RII levels to increase, instigating pro-hypertrophic calcium signaling and concomitant pathological remodeling. Using a combination of in vivo and in vitro approaches, we demonstrated that IP3-induced calcium release (IICR) initiated the hypertrophy-associated decrease in miR-133a. In this manner, hypertrophic stimuli that engage IICR set a feed-forward mechanism in motion whereby IICR decreased miR-133a expression, further augmenting IP3RII levels and therefore pro-hypertrophic calcium release. Consequently, IICR can be considered as both an initiating event and a driving force for pathological remodeling. [ABSTRACT FROM AUTHOR]
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- 2012
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117. MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice.
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Denghong Zhang, Contu, Riccardo, Latronico, Michael V. G., Jian Ling Zhang, Rizzi, Roberto, Catalucci, Daniele, Miyamoto, Shigeki, Huang, Katherine, Ceci, Marcello, Yusu Gu, Dalton, Nancy D., Peterson, Kirk L., Guan, Kun-Liang, Brown, Joan Heller, Ju Chen, Sonenberg, Nahum, Condorelli, Gianluigi, Zhang, Denghong, Zhang, Jianlin, and Zhang, Jian Ling
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RAPAMYCIN , *HEART failure , *APOPTOSIS , *CARRIER proteins , *HEART cells , *HEART physiology , *ANIMAL experimentation , *CELL physiology , *CELLS , *COMPARATIVE studies , *CARDIAC hypertrophy , *RESEARCH methodology , *MEDICAL cooperation , *MICE , *MYOCARDIUM , *PHOSPHOPROTEINS , *PHOSPHORYLATION , *PROTEINS , *RESEARCH , *RESEARCH funding , *TRANSCRIPTION factors , *EVALUATION research , *DILATED cardiomyopathy , *CHEMICAL inhibitors - Abstract
Mechanistic target of rapamycin (MTOR) plays a critical role in the regulation of cell growth and in the response to energy state changes. Drugs inhibiting MTOR are increasingly used in antineoplastic therapies. Myocardial MTOR activity changes during hypertrophy and heart failure (HF). However, whether MTOR exerts a positive or a negative effect on myocardial function remains to be fully elucidated. Here, we show that ablation of Mtor in the adult mouse myocardium results in a fatal, dilated cardiomyopathy that is characterized by apoptosis, autophagy, altered mitochondrial structure, and accumulation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). 4E-BP1 is an MTOR-containing multiprotein complex-1 (MTORC1) substrate that inhibits translation initiation. When subjected to pressure overload, Mtor-ablated mice demonstrated an impaired hypertrophic response and accelerated HF progression. When the gene encoding 4E-BP1 was ablated together with Mtor, marked improvements were observed in apoptosis, heart function, and survival. Our results demonstrate a role for the MTORC1 signaling network in the myocardial response to stress. In particular, they highlight the role of 4E-BP1 in regulating cardiomyocyte viability and in HF. Because the effects of reduced MTOR activity were mediated through increased 4E-BP1 inhibitory activity, blunting this mechanism may represent a novel therapeutic strategy for improving cardiac function in clinical HF. [ABSTRACT FROM AUTHOR]
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- 2010
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118. Peptidomimetic Targeting of Cavβ2 Overcomes Dysregulation of the L-Type Calcium Channel Density and Recovers Cardiac Function
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Magali Cazade, Nicolò Salvarani, Antonio Zaza, Daniele Catalucci, Jean Chemin, Fabio Polticelli, Francesca Rusconi, Silvia Caprari, Elisa Di Pasquale, Giuseppe Faggian, Paola Ceriotti, Michele Miragoli, Marie Louise Bang, Stefano Rossi, Gianluigi Condorelli, Paolo Kunderfranco, Maddalena Tessari, Pierluigi Carullo, Marcella Rocchetti, Humanitas Clinical and Research Center [Rozzano, Milan, Italy], National Research Council [Milan, Italy], University of Parma = Università degli studi di Parma [Parme, Italie], Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), University Hospital of Verona, Università degli Studi Roma Tre, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Rusconi, F, Ceriotti, P, Miragoli, M, Carullo, P, Salvarani, N, Rocchetti, M, Di Pasquale, E, Rossi, S, Tessari, M, Caprari, S, Cazade, M, Kunderfranco, P, Chemin, J, Bang, M, Polticelli, F, Zaza, A, Faggian, G, Condorelli, G, Catalucci, D, Rusconi, Francesca, Ceriotti, Paola, Miragoli, Michele, Carullo, Pierluigi, Salvarani, Nicolò, Rocchetti, Marcella, Di Pasquale, Elisa, Rossi, Stefano, Tessari, Maddalena, Caprari, Silvia, Cazade, Magali, Kunderfranco, Paolo, Chemin, Jean, Bang, Marie Louise, Polticelli, Fabio, Zaza, Antonio, Faggian, Giuseppe, Condorelli, Gianluigi, and Catalucci, Daniele
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0301 basic medicine ,Male ,Peptidomimetic ,[SDV]Life Sciences [q-bio] ,Cell ,030204 cardiovascular system & hematology ,Protein Structure, Secondary ,Mice ,0302 clinical medicine ,Drug Delivery Systems ,HEK293 Cell ,Retrospective Studie ,cardiovascular disease ,Biomimetic Materials ,calcium channels ,Myocytes, Cardiac ,calcium ,L-type ,cardiovascular diseases ,diabetic cardiomyopathies ,drug therapy ,peptides ,protein transport ,Cells, Cultured ,Voltage-dependent calcium channel ,Calcium Channels L-Type ,peptide ,Transport protein ,Cell biology ,medicine.anatomical_structure ,Biochemistry ,Female ,Cardiology and Cardiovascular Medicine ,Protein Structure Secondary ,Biomimetic Material ,Human ,diabetic cardiomyopathie ,Cardiac function curve ,Calcium Channels, L-Type ,chemistry.chemical_element ,Calcium ,Biology ,03 medical and health sciences ,Physiology (medical) ,medicine ,calcium, calcium channels L-type, cardiovascular diseases, diabetic cardiomyopathies, drug therapy, peptides, protein transport, Amino Acid Sequence, Animals, Biomimetic Materials, Calcium Channels L-Type, Cardiovascular Diseases, Cells Cultured, Drug Delivery Systems, Female, HEK293 Cells, Humans, Male, Mice, Mice Inbred C57BL, Myocytes Cardiac, Peptidomimetics, Protein Structure Secondary, Protein Structure Tertiary, Retrospective Studies ,Animals ,Humans ,Mice Inbred C57BL ,L-type calcium channel ,Amino Acid Sequence ,Myocytes Cardiac ,Retrospective Studies ,Animal ,HEK 293 cells ,Protein Structure, Tertiary ,Mice, Inbred C57BL ,Protein Structure Tertiary ,030104 developmental biology ,HEK293 Cells ,chemistry ,Peptidomimetics ,Cells Cultured ,Drug Delivery System - Abstract
Background: L-type calcium channels (LTCCs) play important roles in regulating cardiomyocyte physiology, which is governed by appropriate LTCC trafficking to and density at the cell surface. Factors influencing the expression, half-life, subcellular trafficking, and gating of LTCCs are therefore critically involved in conditions of cardiac physiology and disease. Methods: Yeast 2-hybrid screenings, biochemical and molecular evaluations, protein interaction assays, fluorescence microscopy, structural molecular modeling, and functional studies were used to investigate the molecular mechanisms through which the LTCC Ca v β2 chaperone regulates channel density at the plasma membrane. Results: On the basis of our previous results, we found a direct linear correlation between the total amount of the LTCC pore-forming Ca v α1.2 and the Akt-dependent phosphorylation status of Ca v β2 both in a mouse model of diabetic cardiac disease and in 6 diabetic and 7 nondiabetic cardiomyopathy patients with aortic stenosis undergoing aortic valve replacement. Mechanistically, we demonstrate that a conformational change in Ca v β2 triggered by Akt phosphorylation increases LTCC density at the cardiac plasma membrane, and thus the inward calcium current, through a complex pathway involving reduction of Ca v α1.2 retrograde trafficking and protein degradation through the prevention of dynamin-mediated LTCC endocytosis; promotion of Ca v α1.2 anterograde trafficking by blocking Kir/Gem-dependent sequestration of Ca v β2, thus facilitating the chaperoning of Ca v α1.2; and promotion of Ca v α1.2 transcription by the prevention of Kir/Gem-mediated shuttling of Ca v β2 to the nucleus, where it limits the transcription of Ca v α1.2 through recruitment of the heterochromatin protein 1γ epigenetic repressor to the Cacna1c promoter. On the basis of this mechanism, we developed a novel mimetic peptide that, through targeting of Ca v β2, corrects LTCC life-cycle alterations, facilitating the proper function of cardiac cells. Delivery of mimetic peptide into a mouse model of diabetic cardiac disease associated with LTCC abnormalities restored impaired calcium balance and recovered cardiac function. Conclusions: We have uncovered novel mechanisms modulating LTCC trafficking and life cycle and provide proof of concept for the use of Ca v β2 mimetic peptide as a novel therapeutic tool for the improvement of cardiac conditions correlated with alterations in LTCC levels and function.
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- 2016
119. MicroRNA-133 modulates the β1-adrenergic receptor transduction cascade.
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Castaldi A, Zaglia T, Di Mauro V, Carullo P, Viggiani G, Borile G, Di Stefano B, Schiattarella GG, Gualazzi MG, Elia L, Stirparo GG, Colorito ML, Pironti G, Kunderfranco P, Esposito G, Bang ML, Mongillo M, Condorelli G, and Catalucci D
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- 3' Untranslated Regions physiology, Adenylyl Cyclases physiology, Animals, Apoptosis, Cells, Cultured, Cyclic AMP-Dependent Protein Kinases physiology, Disease Progression, Gene Expression Regulation drug effects, Genes, Reporter, Guanine Nucleotide Exchange Factors physiology, Male, Metoprolol pharmacology, Metoprolol therapeutic use, Mice, Mice, Inbred C57BL, Mice, Transgenic, MicroRNAs genetics, Myocardium metabolism, Myocardium pathology, Myocytes, Cardiac drug effects, RNA, Messenger biosynthesis, RNA, Messenger genetics, Rats, Rats, Sprague-Dawley, Recombinant Fusion Proteins genetics, Cyclic AMP physiology, MicroRNAs physiology, Myocytes, Cardiac physiology, Receptors, Adrenergic, beta-1 physiology, Second Messenger Systems physiology
- Abstract
Rationale: The sympathetic nervous system plays a fundamental role in the regulation of myocardial function. During chronic pressure overload, overactivation of the sympathetic nervous system induces the release of catecholamines, which activate β-adrenergic receptors in cardiomyocytes and lead to increased heart rate and cardiac contractility. However, chronic stimulation of β-adrenergic receptors leads to impaired cardiac function, and β-blockers are widely used as therapeutic agents for the treatment of cardiac disease. MicroRNA-133 (miR-133) is highly expressed in the myocardium and is involved in controlling cardiac function through regulation of messenger RNA translation/stability., Objective: To determine whether miR-133 affects β-adrenergic receptor signaling during progression to heart failure., Methods and Results: Based on bioinformatic analysis, β1-adrenergic receptor (β1AR) and other components of the β1AR signal transduction cascade, including adenylate cyclase VI and the catalytic subunit of the cAMP-dependent protein kinase A, were predicted as direct targets of miR-133 and subsequently validated by experimental studies. Consistently, cAMP accumulation and activation of downstream targets were repressed by miR-133 overexpression in both neonatal and adult cardiomyocytes following selective β1AR stimulation. Furthermore, gain-of-function and loss-of-function studies of miR-133 revealed its role in counteracting the deleterious apoptotic effects caused by chronic β1AR stimulation. This was confirmed in vivo using a novel cardiac-specific TetON-miR-133 inducible transgenic mouse model. When subjected to transaortic constriction, TetON-miR-133 inducible transgenic mice maintained cardiac performance and showed attenuated apoptosis and reduced fibrosis compared with control mice., Conclusions: miR-133 controls multiple components of the β1AR transduction cascade and is cardioprotective during heart failure., (© 2014 American Heart Association, Inc.)
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- 2014
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120. Mutual antagonism between IP(3)RII and miRNA-133a regulates calcium signals and cardiac hypertrophy.
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Drawnel FM, Wachten D, Molkentin JD, Maillet M, Aronsen JM, Swift F, Sjaastad I, Liu N, Catalucci D, Mikoshiba K, Hisatsune C, Okkenhaug H, Andrews SR, Bootman MD, and Roderick HL
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- Animals, Cells, Cultured, HEK293 Cells, Humans, Male, Mice, Mice, Knockout, Mice, Transgenic, MicroRNAs genetics, Rats, Rats, Inbred SHR, Rats, Inbred WKY, Rats, Wistar, Calcium Signaling, Cardiomegaly metabolism, Inositol 1,4,5-Trisphosphate Receptors metabolism, MicroRNAs metabolism
- Abstract
Inositol 1,4,5'-triphosphate receptor II (IP(3)RII) calcium channel expression is increased in both hypertrophic failing human myocardium and experimentally induced models of the disease. The ectopic calcium released from these receptors induces pro-hypertrophic gene expression and may promote arrhythmias. Here, we show that IP(3)RII expression was constitutively restrained by the muscle-specific miRNA, miR-133a. During the hypertrophic response to pressure overload or neurohormonal stimuli, miR-133a down-regulation permitted IP(3)RII levels to increase, instigating pro-hypertrophic calcium signaling and concomitant pathological remodeling. Using a combination of in vivo and in vitro approaches, we demonstrated that IP(3)-induced calcium release (IICR) initiated the hypertrophy-associated decrease in miR-133a. In this manner, hypertrophic stimuli that engage IICR set a feed-forward mechanism in motion whereby IICR decreased miR-133a expression, further augmenting IP(3)RII levels and therefore pro-hypertrophic calcium release. Consequently, IICR can be considered as both an initiating event and a driving force for pathological remodeling.
- Published
- 2012
- Full Text
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121. Interval training normalizes cardiomyocyte function, diastolic Ca2+ control, and SR Ca2+ release synchronicity in a mouse model of diabetic cardiomyopathy.
- Author
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Stølen TO, Høydal MA, Kemi OJ, Catalucci D, Ceci M, Aasum E, Larsen T, Rolim N, Condorelli G, Smith GL, and Wisløff U
- Subjects
- Animals, Cardiomyopathies genetics, Cardiomyopathies physiopathology, Cells, Cultured, Diabetes Complications genetics, Diabetes Complications physiopathology, Diabetes Mellitus, Experimental genetics, Diabetes Mellitus, Experimental physiopathology, Male, Mice, Muscle Proteins metabolism, Phosphorylation, Calcium metabolism, Cardiomyopathies metabolism, Diabetes Complications metabolism, Diabetes Mellitus, Experimental metabolism, Diastole, Myocytes, Cardiac metabolism, Physical Conditioning, Animal, Sarcoplasmic Reticulum metabolism
- Abstract
Rationale: In the present study we explored the mechanisms behind excitation-contraction (EC) coupling defects in cardiomyocytes from mice with type-2 diabetes (db/db)., Objective: We determined whether 13 weeks of aerobic interval training could restore cardiomyocyte Ca(2+) cycling and EC coupling., Methods and Results: Reduced contractility in cardiomyocytes isolated from sedentary db/db was associated with increased diastolic sarcoplasmic reticulum (SR)-Ca(2+) leak, reduced synchrony of Ca(2+) release, reduced transverse (T)-tubule density, and lower peak systolic and diastolic Ca(2+) and caffeine-induced Ca(2+) release. Additionally, the rate of SR Ca(2+) ATPase-mediated Ca(2+) uptake during diastole was reduced, whereas a faster recovery from caffeine-induced Ca(2+) release indicated increased Na(+)/Ca(2+)-exchanger activity. The increased SR-Ca(2+) leak was attributed to increased Ca(2+)-calmodulin-dependent protein kinase (CaMKIIdelta) phosphorylation, supported by the normalization of SR-Ca(2+) leak on inhibition of CaMKIIdelta (AIP). Exercise training restored contractile function associated with restored SR Ca(2+) release synchronicity, T-tubule density, twitch Ca(2+) amplitude, SR Ca(2+) ATPase and Na(+)/Ca(2+)-exchanger activities, and SR-Ca(2+) leak. The latter was associated with reduced phosphorylation of cytosolic CaMKIIdelta. Despite normal contractile function and Ca(2+) handling after the training period, phospholamban was hyperphosphorylated at Serine-16. Protein kinase A inhibition (H-89) in cardiomyocytes from the exercised db/db group abolished the differences in SR-Ca(2+) load when compared with the sedentary db/db mice. EC coupling changes were observed without changes in serum insulin or glucose levels, suggesting that the exercise training-induced effects are not via normalization of the diabetic condition., Conclusions: These data demonstrate that aerobic interval training almost completely restored the contractile function of the diabetic cardiomyocyte to levels close to sedentary wild type.
- Published
- 2009
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122. An adenovirus type 5 (Ad5) amplicon-based packaging cell line for production of high-capacity helper-independent deltaE1-E2-E3-E4 Ad5 vectors.
- Author
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Catalucci D, Sporeno E, Cirillo A, Ciliberto G, Nicosia A, and Colloca S
- Subjects
- Adenoviridae metabolism, Cell Line metabolism, Clone Cells, Epstein-Barr Virus Nuclear Antigens metabolism, Gene Deletion, Genetic Therapy methods, Genetic Vectors metabolism, Hepacivirus metabolism, Humans, Transfection, Viral Proteins metabolism, Adenoviridae genetics, Adenovirus E1 Proteins genetics, Adenovirus E2 Proteins genetics, Adenovirus E3 Proteins genetics, Adenovirus E4 Proteins genetics, Genetic Vectors genetics
- Abstract
Production of multiply deleted adenoviral (Ad) vectors with increased cloning capacity and reduced immunogenicity to adenovirus gene products requires the concomitant generation of efficient packaging cell lines. High expression levels of the complementing genes must be achieved in a coordinated fashion with viral replication. This is a particularly difficult task in light of the significant cytotoxicity displayed by adenoviral proteins. To this end, we developed a novel adenovirus-based amplicon with an Epstein-Barr virus origin of replication, Ad type 5 (Ad5) inverted terminal repeats, all Ad5 early region 2 (E2) genes, and the early region 4 (E4) open reading frame 6 (ORF6) under the control of a tetracycline-dependent promoter. The amplicon (pE2) was stably maintained in multiple copies in the nuclei of 293 cells stably expressing the Epstein-Barr virus nuclear antigen 1 (EBNA1) and allowed replication as a linear DNA upon induction of E2 and ORF6 gene expression. A stable cell line (2E2) was generated by introducing pE2 into 293EBNATet cells expressing the tetracycline-dependent transcriptional silencer and the reverse Tet transactivator (rtTA2). Upon induction with doxicycline, 2E2 cells produced higher levels of polymerase, precursor terminal protein (pTP), and DNA binding protein than noninduced 2E2 cells infected with first-generation Ad5 vector and supported efficient amplification of a multiply deleted Ad5 vector lacking E1, E2, E3, and E4 genes (Ad5DeltaE(1-4)). The high cloning capacity of Ad5DeltaE(1-4) (up to 12.6 kb) was exploited to construct a vector encoding the entire hepatitis C virus (HCV) polyprotein. Infection of HeLa cells by the resulting vector showed high levels of correctly processed HCV proteins.
- Published
- 2005
- Full Text
- View/download PDF
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