Abstract:
:Recovery of intracellular Ca transients and fractional shortening during late phase acidosis are suggested to be associated with CaMKII-dependent processes of which phospholamban (PLB) phosphorylation may play an important role. To test whether increased expression levels of CaMKII may further enhance recovery, we investigated myocytes from CaMKIIdelta(C) transgenic (TG) mice (cytosolic localized CaMKII) having heart failure vs. wild-type littermates (WT). Furthermore, mouse and rabbit myocytes overexpressing CaMKIIdelta(C) using adenovirus-mediated gene transfer (vs. LacZ control) were investigated. Fractional shortening (% vs. resting cell length, % RCL) was assessed during control conditions (pH 7.4) and during acidosis (pH 6.5). Ca transients were measured using fluo-3 (DeltaF/F(0), 10 microM). In WT mouse myocytes, fractional shortening clearly recovered by 90% from 4.6+/-0.6 to 7.2+/-0.7% RCL during late acidosis. In parallel, Ca transients increased from 2.01+/-0.11 to 2.33+/-0.15 DeltaF/F(0). When blocking CaMKII (KN-93, 1 microM), recovery of Ca transients and shortening could be completely abolished. In contrast, in CaMKIIdelta(C) TG mouse myocytes shortening recovered only by 32% from 3.4+/-0.6 to 4.4+/-0.5% RCL (P<0.05 vs. WT using ANOVA). In parallel, Ca transients increased only slightly from 1.75+/-0.15 to 1.84+/-0.13 DeltaF/F(0) (P<0.05 vs. WT using ANOVA). In accordance, SR Ca content (measured by caffeine contractures, 10 mM) in WT significantly increased during late acidosis but not in CaMKIIdelta(C) TG mice. In contrast, in mouse and rabbit myocytes overexpressing CaMKIIdelta(C) by means of adenovirus-mediated gene transfer, recovery of fractional shortening and Ca transients was not impaired during late acidosis but even slightly improved vs. LacZ control (P<0.05 vs. CaMKIIdelta(C) using ANOVA for mouse and rabbit myocytes). This was associated with significantly increased SR Ca content during late acidosis in CaMKIIdelta(C) as compared to LacZ. CaMKII-dependent PLB Thr-17 phosphorylation, contributing to increased SR Ca uptake, was significantly increased in CaMKIIdelta(C) transfected rabbit myocytes vs. LacZ in the light of unchanged SR Ca ATPase and PLB protein expression. CaMKII inhibition completely prevented recovery of all parameters in both CaMKIIdelta(C) and LacZ. In summary and in contrast to our initial hypothesis, we showed for the first time that TG CaMKIIdelta(C) overexpression (i.e., chronic overexpression) in mice with heart failure clearly resulted in impaired recovery associated with impaired SR Ca loading during late acidosis vs. WT. This may be due to decreased SR Ca ATPase and PLB expression as reported previously. In contrast, adenovirus-mediated gene transfer of CaMKIIdelta(C) in mouse and rabbit myocytes (i.e., acute overexpression) did not result in impaired but even slightly improved recovery associated with increased SR Ca load during late acidosis as compared to LacZ. This most likely was due to higher PLB Thr-17 phosphorylation in CaMKIIdelta(C) myocytes. In conclusion, possible beneficial effects by therapeutical CaMKIIdelta(C) stimulation on the ability to recover from acidosis may be challenged by altered expression levels of its target proteins and should be carefully considered.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Sag CM,Dybkova N,Neef S,Maier LSdoi
10.1016/j.yjmcc.2007.09.008subject
Has Abstractpub_date
2007-12-01 00:00:00pages
696-709issue
6eissn
0022-2828issn
1095-8584pii
S0022-2828(07)01239-4journal_volume
43pub_type
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journal_title:Journal of molecular and cellular cardiology
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doi:10.1016/s0022-2828(85)80031-6
更新日期:1985-06-01 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...
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journal_title:Journal of molecular and cellular cardiology
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doi:10.1016/j.yjmcc.2014.08.021
更新日期:2014-11-01 00:00:00
abstract::Microtubules have been implicated in a number of muscle-specific functions, including sarcomerogenesis and the regulation of heart cell beating rate. Post-translationally modified microtubules (MTs) have been correlated, in other cell types, with MTs of increased stability and possibly distinct functions. This study w...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0421
更新日期:1997-06-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.03.014
更新日期:2008-06-01 00:00:00
abstract::Diacylglycerol analogs and phorbol esters are used as protein kinase C (PKC) activators to investigate the effect of PKC on L-type calcium current [ICa(L)] in cardiomyocytes. 1-2-dioctanoyl-sn-glycerol (diC8) is a potent analog of diacylglycerol (DAG) which produces positive inotropic effects in guinea-pig atria cardi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(95)90058-6
更新日期:1995-05-01 00:00:00
abstract::Mitochondrial adenine nucleotide translocase (ANT) is a specific target for the autoantibody response in idiopathic dilated cardiomyopathy (IDCM). We have undertaken an epitope analysis of ANT in IDCM by immunoblot with recombinant GST-ANT fusion proteins and with cellulose-bound decapeptides of human ANT1. Forty-five...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2002.1538
更新日期:2002-05-01 00:00:00
abstract::Mild or low doses of oxidants are known to prime cells towards resistance against further damage. In cardiomyocytes, we found that pretreatment with 100 microM H(2)O(2) prevents the cells from apoptosis induced by doxorubicin (Dox). Affymetrix microarray analyses of 28,000 genes reveal that H(2)O(2) treated cells redu...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.09.012
更新日期:2007-01-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.05.013
更新日期:2010-11-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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更新日期:1992-09-01 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
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2018.03.003
更新日期:2018-05-01 00:00:00
abstract:UNLABELLED:Discrepant results for the phenotype of mitochondrial creatine kinase knockout mice (Mt-CK(-/-)) could be due to mixed genetic background and use of non-littermate controls. We therefore backcrossed with C57BL/6J for >8 generations, followed by extensive in vivo cardiac phenotyping. Echocardiography and in v...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.09.710
更新日期:2009-01-01 00:00:00
abstract::Atrial fibrosis has been strongly associated with the presence of heart diseases/arrhythmias, including congestive heart failure (CHF) and atrial fibrillation (AF). Inducibility of AF as a result of atrial fibrosis has been the subject of intense recent investigation since it is the most commonly encountered arrhythmi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2009.09.001
更新日期:2010-03-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.08.010
更新日期:2018-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.06.003
更新日期:2017-07-01 00:00:00
abstract::The effects of cyclopiazonic acid, a specific inhibitor of the sarcoplasmic reticulum Ca(2+)-ATPase, on membrane currents and contraction were investigated under voltage clamped conditions on frog atrial trabeculae using the double mannitol-gap technique. In ringer solution, cyclopiazonic acid (10 microM) decreased th...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1995.0237
更新日期:1995-11-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0646
更新日期:1998-04-01 00:00:00
abstract::Limited time resolution has hampered proper evaluation of changes in intracellular Na+ (Na+i) in whole hearts upon post-ischemic reperfusion. In isolated rat hearts perfused at 37 degrees C, we studied the contribution of the Na+-K+ ATPase and the Na+-H+ exchanger to control of Na+i during reperfusion using 23Na NMR a...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0597
更新日期:1998-02-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2009.02.021
更新日期:2009-06-01 00:00:00
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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
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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 instability of the oxalate-supported Ca2+ uptake activity of rat cardiac sarcoplasmic reticulum (CSR) in ventricular homogenates most likely accounts for the low specific activity of the rate of oxalate-supported Ca2+ uptake in previously reported fractions of isolated rat CSR. We have found that CSR vesicles with...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(91)90061-p
更新日期:1991-03-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.07.003
更新日期:2004-11-01 00:00:00
abstract::Cardiac myosin-binding protein C (cMyBP-C) is a component of the thick filaments of the sarcomere. Understanding the structural and functional role of cMyBP-C in the heart is clinically relevant since cMyBP-C gene mutations are a widely recognized cause of hypertrophic cardiomyopathy (HCM), which affects 0.2% of the g...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2011.01.014
更新日期:2011-04-01 00:00:00
abstract::Defective sarcoplasmic reticulum (SR) Ca2+ handling is evident in cardiomyopathy and may be mediated by selective dysregulation of SR Ca2+ handling proteins. To assess whether regulation of SR Ca2+ release may vary regionally within the normal and diseased heart, left ventricular transmural expression and activity of ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.04.005
更新日期:2005-08-01 00:00:00
abstract::RP58866 (1-[-2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]-4- (3,4-dimethoxyphenyl)-piperidine), a specific blocker of the inwardly rectifying K+ current (IK1), is an extremely effective antiarrhythmic agent in rat, rabbit and primate (marmoset) isolated hearts in the settings of acute ischaemia and reperfusion (Rees and...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1995.0046
更新日期:1995-12-01 00:00:00
abstract::Oxygen radical-mediated injury has been implicated in the process of cardiac aging. We investigated the tolerance to oxidative stress of hearts from rats of different age. Langendorff-perfused hearts from 3-12-month-old rats received a 30 min infusion of the reactive oxygen specie hydrogen peroxide (H2O2, 60 microM), ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0862
更新日期:1999-01-01 00:00:00
abstract::The kinetics of Ca influx by Na/Ca exchange into adult rat heart cells loaded with Na and depleted of ATP were investigated, to further elucidate how ATP regulates exchanger properties in the intact heart cell. We found an eight-fold reduction in Vmax for Ca uptake by ATP depletion, with no significant change in the K...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0294
更新日期:1997-02-01 00:00:00
abstract::Exposure to carbon monoxide (CO) during the fetal and neonatal period was used to evaluate cardiac ventricular regional weight and myocyte growth response to an increased hemodynamic load. Date-mated Sprague-Dawley rats inhaled 200 ppm CO from day 7 of pregnancy until parturition; another group of pregnant rats inhale...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80913-0
更新日期:1986-05-01 00:00:00