Abstract：
:The insulin receptor substrate (IRS) family plays important roles in cellular growth, signaling, and survival in the brain. We identified IRS6/Dok-5, a member of the IRS family, also expressed in heart. Dok-5 expression level significantly increased during cardiomyocyte differentiation of P19CL6 cells. To understand the mechanism of Dok-5 gene expression and regulation during cardiomyocyte differentiation, we first mapped the transcription start site of the mouse Dok-5 gene and characterized its promoter regions. Truncation and mutation analysis of the Dok-5 promoter identified the forkhead binding element responsible for the repression of Dok-5 promoter activation. The co-localization of FOXO3a and Dok-5 in the mouse heart allows FOXO3a to be a transcriptional regulator of Dok-5. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay confirmed that FOXO3a could bind to the Dok-5 promoter, accompanied by FOXO3a translocation from the nucleus to cytoplasm. FOXO3a overexpression could inhibit Dok-5 promoter activity. Silencing FOXO3a expression by siRNA upregulated the expression of Dok-5 and enhanced cardiomyocyte differentiation. Moreover, Dok-5 siRNA attenuated cardiomyocyte differentiation. Our results provide the first evidence that FOXO3a, the PI3K/PKB downstream substrate, acts as a transcriptional repressor to inhibit the expression of Dok-5. Dok-5 is involved in cardiomyocyte differentiation by a PI3K/PKB/FOXO3a signaling pathway.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Wen J,Xia Q,Wang C,Liu W,Chen Y,Gao J,Gong Y,Yin B,Ke Y,Qiang B,Yuan J,Peng Xdoi
10.1016/j.yjmcc.2009.09.015subject
Has Abstractpub_date
2009-12-01 00:00:00pages
761-9issue
6eissn
0022-2828issn
1095-8584pii
S0022-2828(09)00414-3journal_volume
47pub_type
杂志文章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：:Recent data indicates that DJ-1 plays a role in the cellular response to stress. Here, we aimed to examine the underlying molecular mechanisms mediating the actions of DJ-1 in the heart following myocardial ischemia-reperfusion (I/R) injury. In response to I/R injury, DJ-1 KO mice displayed increased areas of infarcti...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2016.04.008
更新日期：2016-08-01 00:00:00
abstract：:Disturbances of cellular calcium homeostasis due to oxidative stress are involved in reperfusion associated phenomena like myocardial stunning and reperfusion induced arrhythmias. This study investigates the effect of the major neutrophil-derived oxidant hypochlorous acid (HOCl) on the l-type calcium current (ICa,L) o...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0749
更新日期：1998-09-01 00:00:00
abstract：:Atrial fibrillation, the most common sustained arrhythmia, is believed to be triggered by ectopic electrical activity originating in the myocardial sleeves surrounding the pulmonary veins (PVs). It has been reported that myocardial sleeves have the potential to generate automaticity in response to norepinephrine. This...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2012.01.007
更新日期：2012-05-01 00:00:00
abstract：:We have previously reported that resistin induces hypertrophy and impairs contractility in isolated rat cardiomyocytes. To examine the long-term cardiovascular effects of resistin, we induced in vivo overexpression of resistin using adeno-associated virus serotype 9 injected by tail vein in rats and compared to contro...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2011.04.006
更新日期：2011-08-01 00:00:00
abstract：:Cardiac adaptation to aerobic exercise training includes improved cardiomyocyte contractility and calcium handling. Our objective was to determine whether cytosolic calcium/calmodulin-dependent kinase II and its downstream targets are modulated by exercise training. A six-week aerobic interval training program by trea...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2007.06.013
更新日期：2007-09-01 00:00:00
abstract：BACKGROUND:Phosphoinositide 3-kinase α (PI3Kα) is a proto-oncogene with high activity in the heart. BYL719 (BYL) is a PI3Kα-selective small molecule inhibitor and a prospective drug for advanced solid tumors. We investigated whether acute pharmacological inhibition of PI3Kα has pro-arrhythmic effects. METHODS & RESULT...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2019.05.008
更新日期：2019-07-01 00:00:00
abstract：:Mitochondria are central players in the pathophysiology of ischemia-reperfusion. Activation of plasma membrane G-coupled receptors or the Na,K-ATPase triggers cytosolic signaling pathways that result in cardioprotection. Our working hypothesis is that the occupied receptors migrate to caveolae, where signaling enzymes...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2008.11.019
更新日期：2009-06-01 00:00:00
abstract：:Heart failure of diverse causes is associated with abnormalities of sarcoplasmic reticulum (SR) Ca(2+)transport. The purpose of this study was to determine whether the thyroid hormone analogue, 3,5-diiodothyropropionic acid (DITPA), prevents abnormal Ca(2+)transport and expression of SR proteins associated with post-i...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2000.1225
更新日期：2000-11-01 00:00:00
abstract：:The aim of this study was to investigate the effects of aging on the profile of myocardial substrate utilization and cardiac function using a physiological profile of substrates. Hearts from 6-, 15- and 24-month male Wistar rats were perfused in the isovolumic Langendorff mode, with physiological concentrations of 13C...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2005.09.018
更新日期：2006-01-01 00:00:00
abstract：BACKGROUND:Mitochondrial calcium overload is an important factor in defining ischemia/reperfusion injury. Since pre-menopausal women are relatively protected from ischemia and heart disease, we tested the hypothesis that gender differences alter Ca(2+) handling in rat cardiac mitochondria. METHODS:Using cardiac mitoch...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2004.04.023
更新日期：2004-08-01 00:00:00
abstract：:Previous studies have shown that p53 plays an important role in maintaining cell cycle arrest of cardiomyocytes, which might account for the inability of human hearts to regenerate adequately after injury. Therefore, inhibition of p53 represents an attractive strategy to restore cell cycle progression in cardiomyocyte...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2008.06.006
更新日期：2008-09-01 00:00:00
abstract：:Cardiovascular diseases (CVDs) and renal impairment interact in a complex and interdependent manner, which makes clarification of possible pathogenesis between CVDs and renal diseases very challenging and important. There is increasing evidence showing that both asymmetric dimethylarginine (ADMA) and symmetric dimethy...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2017.09.010
更新日期：2017-12-01 00:00:00
abstract：:The heart contains many cell types; mechanical work is done by cardiomyocytes which do not divide but are terminally differentiated and capable of continuous protein synthesis and degradation. The steps in protein synthesis are (1) transport of amino acids into heart cells by a variety of cell-membrane carriers, (2) A...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/s0022-2828(84)80711-7
更新日期：1984-01-01 00:00:00
abstract：:A number of endogenous mediators, including opioids, adenosine and bradykinin, which act on cardiac cell membrane receptors have been demonstrated to trigger the phenomenon termed ischemic preconditioning (IPC). IPC is an endogenous protective mechanism, whereby a brief period of ischemia or hypoxia protects a cell or...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/s0022-2828(03)00135-4
更新日期：2003-07-01 00:00:00
abstract：:Mitochondria are highly metabolically active cell organelles that not only act as the powerhouse of the cell by supplying energy through ATP production, but also play a destructive role by initiating cell death pathways. Growing evidence recognizes that mitochondrial dysfunction is one of the major causes of cardiovas...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2011.09.007
更新日期：2012-02-01 00:00:00
abstract：:Vascular tone is regulated by a variety of neurotransmitters, vasoactive hormones and autacoids, and vasoactive drugs. These actions are mediated, at least in part, by actions on the membrane ion channels, exerted either directly or indirectly. In this article, we described evidence that four different protein kinase ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/s0022-2828(08)80009-0
更新日期：1995-01-01 00:00:00
abstract：:Endothelin-1 (ET-1) is a potent agonist of cell growth that also stimulates Na(+)/H(+) exchanger isoform 1 (NHE-1) activity. It was hypothesized that the increase in intracellular Na(+) ([Na(+)](i)) mediated by NHE-1 activity may induce the reverse mode of Na(+)/Ca(2+) exchanger (NCX(rev)) increasing intracellular Ca(...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2006.05.016
更新日期：2006-11-01 00:00:00
abstract：:Nitrovasodilators relax vascular smooth muscle by stimulating guanylate cyclase. Ignarro et al. (1981) proposed a mechanistic scheme according to which organic nitrates release nitrite in the presence of thiols. The corresponding nitrous acid would decay leading to nitric oxide, which then would react with another thi...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(88)80130-5
更新日期：1988-05-01 00:00:00
abstract：:We have investigated whether translocation of constitutive low molecular weight stress proteins (alphaB-crystallin and HSP27) to the myofilament/cytoskeletal compartment occurs during ischemic preconditioning and assessed if this is causally associated with cardioprotection. Triton-insoluble preparations from fresh or...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2000.1136
更新日期：2000-06-01 00:00:00
abstract：:We have identified in soluble extracts of rat heart, a 500 000 dalton sulfhydryl-dependent protease which degrades globin and casein to acid-soluble peptides at an alkaline pH optimum. This enzyme was purified more than 1700-fold with respect to the postmicrosomal supernatant. On the basis of various catalytic and bio...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(83)90304-8
更新日期：1983-01-01 00:00:00
abstract：:The contribution of endogenous NO to ischemia-reperfusion injury was studied in isolated perfused hearts of wild-type (WT) and endothelial NO synthase knockout (eNOS-) mice. The hearts were subjected to a 16-min period of global no-flow ischemia and were subsequently reperfused for 1 h. Cardiac contractile function wa...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0921
更新日期：1999-04-01 00:00:00
abstract：:We studied peripheral skeletal muscle metabolism in monocrotaline-treated rats. Two distinct groups emerged: a percentage of the animals developed ventricular hypertrophy, with no signs of heart failure (compensated group), whilst others, besides ventricular hypertrophy, developed the syndrome of congestive heart fail...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1996.0219
更新日期：1996-11-01 00:00:00
abstract：:While much is known about the deleterious effects of pro-inflammatory cytokines on development of vascular disease, little is reported on the direct effects of anti-inflammatory cytokines on the vascular smooth muscle cell (VSMC) response to injury. Interleukin-19 (IL-19) is a recently described Th2, anti-inflammatory...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2010.04.016
更新日期：2010-10-01 00:00:00
abstract：:The binding properties of [3H]U69593, a selective k-ligand, in rat heart homogenates were characterized by direct and displacement receptor binding assays. It was found that there are substantial specific [3H]U69593 binding sites in the rat heart. They were saturable, reversible and stereospecific. Both association an...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(91)90086-2
更新日期：1991-11-01 00:00:00
abstract：:Human immunodeficiency virus (HIV, lentivirus) type-1 based vectors have a number of attractive features for gene therapy, including the ability to transduce non-dividing cells and long term transgene expression. We used a three-plasmid expression system to generate pseudotyped lentivirus-based vectors by transient tr...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1999.1035
更新日期：1999-11-01 00:00:00
abstract：:Cardiac hypertrophy is characterized, among others, by the molecular events which selectively activate the expression of genes for contractile proteins within individual myocardial cells. As such, myosin light chain 2 (MLC-2), which is upregulated in the hypertrophic state in both rat and human, serves as a marker for...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(95)92019-6
更新日期：1995-10-01 00:00:00
abstract：:Heart failure is associated with mitochondrial dysfunction so that restoring or improving mitochondrial health is of therapeutic importance. Recently, reduction in NAD+ levels and NAD+-mediated deacetylase activity has been recognized as negative regulators of mitochondrial function. Using a cardiac specific KLF4 defi...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2017.09.001
更新日期：2017-11-01 00:00:00
abstract：:The 23Na NMR shift-reagent complexes (Dy(PPP)2, Dy(TTHA), and Tm(DOTP)) bind stoichiometric amounts of Ca2+. Thus, in perfused rat heart systems, a supplementation of Ca2+ is required to maintain the requisite extracellular free calcium concentration ([Ca(o)]f) and to approximate a physiological level of contractile f...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2001.1459
更新日期：2001-11-01 00:00:00
abstract：:Acute right ventricular (RV) failure following pulmonary embolism (PE) is a strong predictor of poor clinical outcome. Present studies test for an association between RV failure from experimental PE, inflammation, and upregulated chemokine expression. Additional experiments test if neutrophil influx contributes to RV ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2006.05.011
更新日期：2006-08-01 00:00:00
