Abstract：
:Cardiomyocytes represent one of the most useful models to conduct cardiac research. A single adult heart yields millions of cardiomyocytes, but these cells do not survive for long after isolation. We aimed to determine whether inhibition of myosin II ATPase that is essential for muscle contraction may preserve fully differentiated adult cardiomyocytes. Using inhibitors of the myosin II ATPase, blebbistatin and N-benzyl-p-toluene sulphonamide (BTS), we preserved freshly isolated fully differentiated adult primary cardiomyocytes that were stored at a refrigerated temperature. Specifically, preserved cardiomyocytes stayed viable for a 2-week period with a stable expression of cardiac genes and retained the expression of key markers characteristic of cardiomyocytes. Furthermore, voltage-clamp, action potential, calcium transient and contractility studies confirmed that the preserved cardiomyocytes are comparable to freshly isolated cells. Long-term exposure of preserved cardiomyocytes to four tyrosine kinase inhibitors, sunitinib malate, dasatinib, sorafenib tosylate and imatinib mesylate, revealed their potential to induce cardiac toxicity that was manifested with a decrease in contractility and induction of cell death, but this toxicity was not observed in acute experiments conducted over the time course amenable to freshly prepared cardiomyocytes. This study introduces the concept that the inhibition of myosin II ATPase safeguards the structure and function of fully differentiated adult cardiomyocytes. The fact that these preserved cardiomyocytes can be used for numerous days after preparation makes them a robust and versatile tool in cardiac research and allows the investigation of long-term exposure to novel drugs on cardiomyocyte function.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Abi-Gerges N,Pointon A,Pullen GF,Morton MJ,Oldman KL,Armstrong D,Valentin JP,Pollard CEdoi
10.1016/j.yjmcc.2013.09.004subject
Has Abstractpub_date
2013-11-01 00:00:00pages
108-19eissn
0022-2828issn
1095-8584pii
S0022-2828(13)00267-8journal_volume
64pub_type
杂志文章abstract：:Atrial cardiac myocytes secrete the vasoactive hormone atrial natriuretic peptide (ANP) by both constitutive and regulated exocytotic fusion of ANP-containing large dense core vesicles (LDCV) with the sarcolemma. Detailed information, however, regarding the identity and function of specific membrane fusion proteins (S...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2005.12.007
更新日期：2006-03-01 00:00:00
abstract：:This study addressed the question whether the molecular mass of proteins influences their release from isolated rat neonatal cardiomyocytes subjected to simulated ischemia (SI) or metabolic inhibition (MI). During these interventions cellular ATP content and the relative releases of several proteins, ranging in molecu...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1996.0133
更新日期：1996-07-01 00:00:00
abstract：:We studied post-extrasystolic potentiation (PESP) and frequency potentiation (FP) of human working myocardium isolated from the ventricles of 10 patients with end-stage heart failure (CHF) and 17 non-failing controls (CTL). The contractility index was peak isometric tension developed in vitro by trabeculae carneae (CT...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(90)90975-8
更新日期：1990-01-01 00:00:00
abstract：:The concept of metabolic protection of the ischemic myocardium is in constant evolution and has recently been supported by clinical studies. Historically, enhanced glucose metabolism and glycolysis were proposed as anti-ischemic cardioprotection. This hypothesis is supported by the sub-cellular linkage between key gly...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1006/jmcc.2002.2066
更新日期：2002-09-01 00:00:00
abstract：:Increasing bodies of evidence indicate that reactive oxygen species (ROS) produced by mitochondria and other sources play an essential role in mediating ventricular remodeling after myocardial infarction and the development of heart failure. Antioxidants scavenge ROS, thereby maintaining the reduced environment of cel...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2006.08.006
更新日期：2006-11-01 00:00:00
abstract：:Identification of proteins that interact with Cx43 has been instrumental in the understanding of gap junction (GJ) regulation. An in vitro phosphorylation screen identified that Protein tyrosine kinase 2 beta (Pyk2) phosphorylated purified Cx43CT and this led us to characterize the impact of this phosphorylation on Cx...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2020.09.004
更新日期：2020-12-01 00:00:00
abstract：:This study was designed to examine whether diltiazem, a calcium channel-blocker, inhibits the cardiac ultrastructural alterations induced by coronary occlusion with or without reperfusion, in dogs anesthetized with pentobarbital. The left anterior descending coronary artery (LAD) was completely occluded for 60 min wit...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(86)80903-8
更新日期：1986-04-01 00:00:00
abstract：:Cardiac arrhythmias are one of the main causes of death worldwide. Several studies have shown that inflammation plays a key role in different cardiac diseases and Toll-like receptors (TLRs) seem to be involved in cardiac complications. In the present study, we investigated whether the activation of TLR4 induces cardia...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2014.08.012
更新日期：2014-11-01 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：:The opening of mitochondrial permeability transition pore (PTP) during reperfusion injury of heart has been well demonstrated and thus controlling PTP would attenuate the myocardial damage and cell death. Ursodeoxycholic acid (UDCA) is a hydrophilic bile salt and has been shown to prevent apoptosis in hepatocytes by i...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2005.07.014
更新日期：2005-11-01 00:00:00
abstract：RATIONALE:Truncation mutations in the MYBPC3 gene, encoding for cardiac myosin-binding protein C (MyBP-C), are the leading cause of hypertrophic cardiomyopathy (HCM). Whole heart, fiber and molecular studies demonstrate that MyBP-C is a potent modulator of cardiac contractility, but how these mutations contribute to HC...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2018.12.003
更新日期：2019-02-01 00:00:00
abstract：:Cardiac sarcoplasmic reticulum (SR) sequesters Ca2+ and plays a crucial role in the regulation of intracellular Ca2+. Its functional properties are central to the excitation-contraction (E-C) cycle of cardiac muscle. In this study, we examined the hypothesis that alterations in SR function occur during the development...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1996.0250
更新日期：1997-01-01 00:00:00
abstract：:(1) The effects of norepinephrine on protein phosphorylation in isolated rat cardiac ventricular myocytes were determined by autoradiography on 32P-labelled proteins separated by electrophoresis; (2) In cells from young adult rats (6 months old) there was a marked increase due to norepinephrine (10(-8) to 10(-4) M) in...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(89)90678-0
更新日期：1989-12-01 00:00:00
abstract：:The effects of trimetazidine on membrane potentials and membrane currents of enzymatically isolated guinea-pig ventricular cells were studied with the use of giga-seal suction pipettes for patch clamp. Trimetazidine (3 X 10(-5) M) decreased the action potential duration from 433 +/- 179 ms (mean and S.D., n = 9) to 31...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(86)80433-3
更新日期：1986-12-01 00:00:00
abstract：:AT1 receptor blockers (ARB) and in part ACE inhibitors (ACI) potentially exert beneficial effects on atherogenesis independent of AT1 receptor inhibition. These pleiotropic effects might be related to angiotensin II mediated activation of the AT2 receptor. To analyze this hypothesis we investigated the development of ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2011.12.007
更新日期：2012-03-01 00:00:00
abstract：:The aim of this study was to examine whether short- and long-term gene transfer of Ca(2+) handling proteins restore left ventricular (LV) mechanoenergetics in aortic banding-induced failing hearts. Aortic-banded rats received recombinant adenoviruses carrying sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) (Banding+SER...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2007.01.003
更新日期：2007-04-01 00:00:00
abstract：:Diabetic cardiomyopathy is responsible for substantial morbidity and mortality in the diabetic population. Increased oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. Multiple biochemical mechanisms have been proposed to increase oxidative stress in ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2003.09.007
更新日期：2003-12-01 00:00:00
abstract：:The correlations between myocardial redox and energy states and atrial natriuretic peptide (ANP) secretion were studied in the perfused rat heart by exposing the hearts to global and low-flow ischemia for varying periods. Atrial and ventricular energy states and immunoreactive ANP in the effluent perfusate were measur...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(92)93155-d
更新日期：1992-02-01 00:00:00
abstract：:Nitric oxide plays a crucial role in myocardial ischemia reperfusion injury as well as in myocardial adaptation to ischemic stress. To understand the dichotomy of nitric oxide behavior in the ischemic myocardium, isolated rat hearts were subjected to ischemia/reperfusion protocol. The tissue contents of sphingomyelin ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2005.10.005
更新日期：2006-02-01 00:00:00
abstract：:Inhibition of I(K1) currents by adrenergic alpha(1) receptors has been observed in cardiomyocytes and has been linked to arrhythmogenesis in an animal model. Both PKC-dependent and PKC-independent pathways have been implied in this regulation. The underlying molecular mechanisms, however, have not been elucidated to d...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2007.10.008
更新日期：2008-01-01 00:00:00
abstract：:This study examined the hypothesis that the prediabetic metabolic syndrome alters expression, phosphorylation state and binding affinity of cardiac RyR2. Real-time PCR and Western blot analysis were used to assess mRNA and protein expression in the left ventricle, right ventricle and right atrium from control (n=5) an...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2006.04.018
更新日期：2006-07-01 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：:The aim of the study was to test if pre-ischemic treatment with bradykinin can protect against infarction in an isolated rat heart model of regional ischemia and reperfusion, and if any such protection is dependent upon activation of protein kinase C (PKC) or mediated through the nitric oxide (NO) pathway. We also inv...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1996.0226
更新日期：1996-12-01 00:00:00
abstract：:In the mouse, genetic reduction in the Na(+), K(+)-ATPase alpha1 or alpha2 isoforms results in different functional phenotypes: heterozygous alpha2 isolated hearts are hypercontractile, whereas heterozygous alpha1 hearts are hypocontractile. We examined Na(+)/Ca(2+) exchange (NCX) currents in voltage clamped myocytes ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2005.03.023
更新日期：2005-07-01 00:00:00
abstract：:Rapamycin (Sirolimus®) is used to prevent rejection of transplanted organs and coronary restenosis. We reported that rapamycin induced cardioprotection against ischemia-reperfusion (I/R) injury through opening of mitochondrial K(ATP) channels. However, signaling mechanisms in rapamycin-induced cardioprotection are cur...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2012.09.007
更新日期：2012-12-01 00:00:00
abstract：RATIONALE:A higher expression/activity of type 1 serine/threonine protein phosphatase 1 (PP1) may contribute to dephosphorylation of cardiac regulatory proteins triggering the development of heart failure. OBJECTIVE:Here, we tested the putatively protective effects of PP1 inhibitor-2 (I2) overexpression using a heart ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2018.10.022
更新日期：2018-12-01 00:00:00
abstract：:The currently used biomarkers for acute myocardial infarction (AMI) are blood creatinine phosphokinase-muscle band (CPK-MB), troponin-T (TnT), and troponin I (TnI). However, no good biomarkers are identified in urine after AMI, because these blood protein biomarkers are difficult to be filtered into urine. In this stu...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2012.08.010
更新日期：2012-11-01 00:00:00
abstract：:The aim of this study was: (1) to elucidate in more detail the relationship between stress protein expression and brief periods of ischaemia and reperfusion, such as occur during early (classical) ischaemic preconditioning (PC) in the rabbit myocardium; (2) to determine whether stress protein expression is affected by...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(95)91299-1
更新日期：1995-10-01 00:00:00
abstract：:Baroreflex control of heart rate was studied in conscious diabetic rats at 12, 24 and 48 weeks after the induction of diabetes with streptozotocin. Baseline blood pressure (mean arterial blood pressure) of diabetic rats was significantly lower at 12 weeks after the induction of diabetes when compared to age-matched co...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(86)80969-5
更新日期：1986-06-01 00:00:00
abstract：BACKGROUNDS:Low serum cholesterol levels are associated with cardiac arrhythmias and poor prognosis in patients with chronic heart failure. However, the underlying mechanisms by which decreases in cholesterol content lead to cardiac dysfunction remain unclear. Multiple studies have implicated damage to cardiac transver...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2016.05.013
更新日期：2016-08-01 00:00:00
