Abstract:
:Fibroblast growth factor receptor 1 (FGFR1) is the only high-affinity FGFR in the vertebrate myocardium. FGFR1 is a tyrosine kinase receptor and has a non-redundant role in proliferation and differentiation of cardiomyocytes during embryogenesis. Results presented here demonstrate that FGFR1 gene expression declines as neonatal cardiomyocytes develop into adult cardiomyocytes. Furthermore, silencing FGFR1 gene expression reduced neonatal cardiomyocyte proliferation, indicating that FGFR1 gene expression is required for the optimal proliferative capacity of cardiomyocytes. To determine the mechanism that governs FGFR1 gene expression in cardiomyocytes, sequence analysis of the proximal mouse FGFR1 promoter identified a potential binding site for Sp transcription factors. Mutation of this site increased FGFR1 promoter activity compared to the wild-type promoter, indicating the presence of a negative transcriptional regulator of the FGFR1 promoter at this site in cardiomyocytes. Sp3 expression in neonatal cardiomyocytes and Drosophila SL2 cells reduced FGFR1 promoter activity in a dose-dependent manner. Western blots and immunocytochemistry indicated that Sp3 was present in the nuclear and cytoplasmic compartments of neonatal cardiomyocytes. Chromatin-immunoprecipitation studies verified that endogenous Sp3 in cardiomyocytes interacts with the FGFR1 promoter. Transient chromatin-immunoprecipitation studies using wild-type and mutated FGFR1 promoter constructs in SL2 cells identified the specific Sp3 binding site within the FGFR1 promoter. These studies implicate Sp3 as a negative transcriptional regulator of FGFR1 promoter activity in cardiomyocytes and as a suppressor of cardiomyocyte proliferation.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Seyed M,Dimario JXdoi
10.1016/j.yjmcc.2007.12.008subject
Has Abstractpub_date
2008-03-01 00:00:00pages
510-9issue
3eissn
0022-2828issn
1095-8584pii
S0022-2828(08)00003-5journal_volume
44pub_type
杂志文章abstract::Since systemic actions of thyroid hormone increase cardiac work, direct effects of T3 on myocardial protein turnover may be obscured in the intact animal. For this reason, the effects of T3 on synthesis and degradation of cellular protein were measured in replicate cultures of cardiac myocytes obtained from chick embr...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(85)80103-6
更新日期:1985-09-01 00:00:00
abstract::Extracellular superoxide dismutase (EC-SOD) is an antioxidant that protects the heart from ischemia and the lung from inflammation and fibrosis. The role of cardiac EC-SOD under normal conditions and injury remains unclear. Cardiac toxicity, a common side effect of doxorubicin, involves oxidative stress. We hypothesiz...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.08.010
更新日期:2009-11-01 00:00:00
abstract::The incidence of ventricular arrhythmias is higher in failing hearts than in control hearts, especially during acute ischemia. Electrophysiological and extracellular ionic changes during acute ischemia in normal and failing rabbit myocardium were assessed. Heart failure was induced in rabbits by combined volume and pr...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0012
更新日期:1996-01-01 00:00:00
abstract::Phospholipase D (PLD) plays a central role in receptor-mediated breakdown of choline phospholipids and formation of phosphatidic acid (PA), an important regulator of cardiac function. However, specific mechanisms that regulate myocardial PLD activity remain largely unknown, particularly in the human heart. We hypothes...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2003.11.008
更新日期:2004-02-01 00:00:00
abstract::Myocardial infarction (MI) provokes regional inflammation which facilitates the healing, whereas excessive inflammation leads to adverse cardiac remodelling. Our aim was to determine the role of macrophage migration inhibitory factor (MIF) in inflammation and cardiac remodelling following MI. Wild type (WT) or global ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.01.015
更新日期:2014-04-01 00:00:00
abstract::We studied the presence of collagen degrading enzymes (matrix metalloproteinases, MMPs) in porcine myocardium following ischemia and late reperfusion. In nine pigs, left anterior descending coronary artery was occluded for 6 h followed by reperfusion for 3 h. Six pigs without coronary occlusion served as controls. Aft...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0711
更新日期:1998-07-01 00:00:00
abstract::During systole, Ca2+ is released from the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) while, simultaneously, other ions (specifically K+, Mg2+, and Cl-) provide counter-ion flux. These ions move back into the SR during diastole through the SERCA pump and SR K+ and Cl- channels. In homeostasis, all i...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2016.10.018
更新日期:2017-02-01 00:00:00
abstract::Mitochondria-generated reactive oxygen species (ROS) play a crucial role in the pathogenesis of aging and age-associated diseases. In this study, we evaluated the effects of XJB-5-131 (XJB), a mitochondria-targeted ROS and electron scavenger, on cardiac resistance to ischemia-reperfusion (IR)-induced oxidative stress ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.10.009
更新日期:2014-12-01 00:00:00
abstract::Reperfusion or reoxygenation of ischaemic or hypoxic cardiac tissue results in increases in total cell calcium and cell lysis both of which are dependent on mitochondrial function. Although changes which occur during this period of exposure of the tissue to hypoxia predispose the heart to take up calcium on reoxygenat...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1993.1107
更新日期:1993-08-01 00:00:00
abstract::Pathologic cardiac hypertrophy can lead to heart failure, but the mechanisms involved are poorly understood. SERCA2 is critical for normal cardiac calcium handling and function and SERCA2 mRNA and protein levels are reduced by cardiac hypertrophy. We hypothesized that extracellular signal-regulated kinase (ERK) 1/2 ac...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.06.018
更新日期:2014-10-01 00:00:00
abstract::The lack of pathological consequences of cardiac ATP-sensitive potassium channel (K(ATP)) channel gene manipulation is in stark contrast to the effect of similar perturbations in the pancreatic beta-cell. Because the pancreatic and cardiac channel share the same pore-forming subunit (Kir6.2), the different effects of ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.06.003
更新日期:2005-10-01 00:00:00
abstract::Satellite cells from adult mouse tongue, diaphragm, vastus lateralis, rectus femoris, tibialis anterior, soleus, and extensor digitorum longus muscles were isolated, expanded, and differentiated under identical culture conditions. Proliferating myoblasts and differentiated myofiber cultures were analyzed via SDS-PAGE,...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(03)00245-1
更新日期:2003-10-01 00:00:00
abstract::Fibroblast growth factor receptor (FGFR) is expressed in a variety of cells and is involved in their proliferation/migration/survival. To elucidate FGFR-mediated specific action of vascular endothelial cells (ECs) on myocardial ischemia, we generated endothelium-targeted transgenic mice overexpressing constitutively a...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.01.015
更新日期:2009-05-01 00:00:00
abstract::The present study was undertaken to assess whether [32P]uptake and autoradiography could be used as an indicator of regional myocardial oxygen consumption. Rat hearts were perfused in the Langendorff mode with medium containing [32P]orthophosphate (32Pi) and the incorporation of label into ATP, perchloric acid-insolub...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1993.1035
更新日期:1993-03-01 00:00:00
abstract::Cardiac hypertrophy has been well-characterized at the level of transcription. During cardiac hypertrophy, genes normally expressed primarily during fetal heart development are re-expressed, and this fetal gene program is believed to be a critical component of the hypertrophic process. Recently, alternative splicing o...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2013.05.004
更新日期:2013-09-01 00:00:00
abstract::Although captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been shown to exert a beneficial effect on cardiac function in heart failure, its effect on the status of sarcoplasmic reticulum (SR) Ca(2+) transport in the failing heart has not been examined previously. In order to determine whether captopril...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.1000
更新日期:1999-09-01 00:00:00
abstract::The Na+/Ca2+ exchanger plays an important role in the maintenance of calcium homeostasis in the heart. Therefore, factors which regulate the exchanger have a significant impact on cardiac function. Previously, we showed that the non-hydrolysable GTP analog, 5'guanylyl imidodiphosphate [Gpp(NH)p], stimulates Na+/Ca2+ e...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0002
更新日期:1996-01-01 00:00:00
abstract::Energy metabolism of quiescent cardiac muscle was studied in the isolated rabbit heart preparation perfused at constant pressure by the Langendorff technique. Oxygen consumption (MVo2), coronary flow rate (CFR) and the steady state concentrations of high energy phosphate compounds were determined in hearts rendered as...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90863-8
更新日期:1989-02-01 00:00:00
abstract::Fibrillar collagens, essential for maintaining the structural integrity of the myocardium, are degraded by matrix metalloproteinase (MMP-1). In other tissues collagenolysis is an important component of wound healing. Here we examined collagen degradation in the myocardium after infarction. Collagenase activity, measur...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(05)82390-9
更新日期:1995-06-01 00:00:00
abstract::The ability of human pluripotent stem cells (hPSCs) to differentiate into any cell type of the three germ layers makes them a very promising cell source for multiple purposes, including regenerative medicine, drug discovery, and as a model to study disease mechanisms and progression. One of the first specialized cell ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2013.12.011
更新日期:2014-02-01 00:00:00
abstract::The right ventricle (RV) differs in several aspects from the left ventricle (LV) including its embryonic origin, physiological role and anatomical design. In contrast to LV hypertrophy, little is known about the molecular circuits, which are activated upon RV hypertrophy (RVH). We established a highly reproducible mod...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.07.014
更新日期:2010-10-01 00:00:00
abstract::Celecoxib is a COX-2 inhibitor that has been related to an increased cardiovascular risk and that exerts several actions on different targets. The aim of this study was to analyze the effects of this drug on human cardiac voltage-gated potassium channels (Kv) involved on cardiac repolarization Kv1.5 (I(Kur)), Kv4.3+KC...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.09.012
更新日期:2010-12-01 00:00:00
abstract::Our previous work in cultured cells has shown that the maintenance of mitochondrial Ca(2+) homeostasis is essential for cell survival, and that the anti-apoptotic protein Bcl-2 is able to maintain a threshold level of mitochondrial Ca(2+) by the inhibition of permeability transition. To test whether Bcl-2 also affects...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1476
更新日期:2001-12-01 00:00:00
abstract::The atrioventricular conduction axis, located in the septal component of the atrioventricular junctions, is arguably the most complex structure in the heart. It fulfils a multitude of functions, including the introduction of a delay between atrial and ventricular systole and backup pacemaking. Like any other multifunc...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.12.017
更新日期:2011-04-01 00:00:00
abstract::Reactive oxygen species (ROS) play an important role in cardiovascular diseases, and one important source for ROS are mitochondria. Emission of ROS from mitochondria is the net result of ROS production at the electron transport chain (ETC) and their elimination by antioxidative enzymes. Both of these processes are hig...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2014.03.011
更新日期:2014-08-01 00:00:00
abstract::Hypothermic cardioplegic solutions are currently used to preserve cardiac function during transportation. However, it has been shown that end-diastolic compliance decreases in donor hearts during reperfusion. Excessively cold temperatures may affect membrane-bound enzymes (Ca2+ ATPase and Ca2+ uptake) which are necess...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1993.1129
更新日期:1993-10-01 00:00:00
abstract::In the present investigation, the effects of forskolin on intracellular sodium activity were studied in quiescent and electrically stimulated cardiac Purkinje fibers from sheep using Na+-sensitive microelectrodes. Also assessed, were the effects of this promoter of cytosolic cAMP production on resting membrane potenti...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(87)80617-x
更新日期:1987-09-01 00:00:00
abstract::To establish new treatment for cardiovascular disease, the development of safe and highly efficient vectors is necessary. Especially, non-viral vectors are considered to be ideal for human gene therapy, since recent adverse events with retroviral or adenoviral vectors have highlighted the issue of safety. Although we ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.06.007
更新日期:2005-09-01 00:00:00
abstract::Various drugs are reported to prolong the QT-interval on the surface ECG, thereby increasing the risk of developing a potentially fatal arrhythmia known as Torsades de Pointes (TdP). TdP case reports for these drugs have often been associated with risk factors such as overdosing, concomitant drugs and/or existing path...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.09.001
更新日期:2004-11-01 00:00:00
abstract::This study addresses the role of polyamines and their rate limiting enzyme, ornithine decarboxylase in regulation of macromolecular transport of two macromolecules, fluorescein and horseradish peroxidase, across coronary capillaries. Rat hearts were isolated and retrogradely perfused through the aorta (Langendorff met...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1046
更新日期:1994-03-01 00:00:00