Abstract:
:Cardiac myosin binding protein C (cMyBP-C) phosphorylation is differentially regulated in the normal heart and during disease development. Our objective was to examine in detail three phosphorylatable sites (Ser-273, Ser-282, and Ser-302) present in the protein's cardiac-specific sequences, as these residues are differentially and reversibly phosphorylated during normal and abnormal cardiac function. Three transgenic lines were generated: DAA, which expressed cMyBP-C containing Asp-273, Ala-282, and Ala-302, in which a charged amino acid was placed at residue 273 and the remaining two sites rendered nonphosphorylatable by substituting alanines for the two serines; AAD containing Ala-273, Ala-282, and Asp-302, in which aspartate was placed at residue 302 and the remaining two sites rendered nonphosphorylatable; and SDS containing Ser-273, Asp-282, and Ser-302. These mice were compared to mice constructed previously along similar lines: wild type, in which normal cMyBP-C is transgenically expressed, AllP-, in which alanines were substituted and ADA mice as well. DAA and AAD mice showed pathology that was more severe than cMyBP-C nulls. DAA and AAD animals exhibited left ventricular chamber dilation, interstitial fibrosis, irregular cardiac rhythm and sudden cardiac death. Our results define the effects of the sites' post-translational modifications on cMyBP-C functionality and together, give a comprehensive picture of the potential consequences of site-specific phosphorylation. Ser-282 is a key residue in controlling S2 interaction with the thick and thin filaments. The new DAA and AAD constructs show that phosphorylation at one site in the absence of the ability to phosphorylate the other sites, depending upon the particular residues involved, can lead to severe cardiac remodeling and dysfunction.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Gupta MK,Gulick J,James J,Osinska H,Lorenz JN,Robbins Jdoi
10.1016/j.yjmcc.2013.08.006subject
Has Abstractpub_date
2013-11-01 00:00:00pages
39-50eissn
0022-2828issn
1095-8584pii
S0022-2828(13)00259-9journal_volume
64pub_type
杂志文章abstract::Immediate post-receptor events following alpha-adrenoceptor stimulation in cardiac ventricular muscle are still largely unknown. Since membrane redox systems appear to be present in cell plasma membranes and may be involved in trans-sarcolemma electron efflux, the possibility that Ca2+ inflow was controlled by electro...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80462-x
更新日期:1986-11-01 00:00:00
abstract::Human vascular connexins (Cx37, Cx40, Cx43, and Cx45) can form various types of gap junction channels to synchronize vasodilation/constriction to control local circulation. Most of our knowledge on heterotypic gap junctions of these vascular connexins was from studies on rodent connexins. In human vasculature, the sam...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.12.013
更新日期:2019-02-01 00:00:00
abstract::Endothelial dysfunction is the earliest pathologic alteration in diabetic vascular injury and plays a critical role in the development of atherosclerosis. Plasma levels of adiponectin (APN), a novel vasculoprotective adipocytokine, are significantly reduced in diabetic patients, but its relationship with endothelial d...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.10.014
更新日期:2009-03-01 00:00:00
abstract::We have previously shown that domains involved in binding of protein kinase C (PKC) isozymes to their respective anchoring proteins (RACKs) and short peptides derived from these domains are PKC isozyme-selective antagonists. We also identified PKC isozyme-selective agonists, named psiRACK peptides, derived from a sequ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.01.007
更新日期:2007-04-01 00:00:00
abstract::Arterial hypotension can cause cerebral ischemia when the autoregulation of the cerebral circulation is exhausted. We hypothesized that sudden cerebral vasoconstriction induced by moderate hypotensive, but hemodynamically stable, sustained ventricular tachycardias (MHT-VT) further compromises cerebral blood flow (CBF)...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0772
更新日期:1998-10-01 00:00:00
abstract::Although several studies have demonstrated that nitric oxide appears to be cardioprotective and endothelin-1 (ET-1) deleterious in myocardial ischemia/reperfusion injury, their interactions in the intact heart are unknown. Therefore, coronary effluent and interstitial fluid ("transudate") levels of ET-1 and cyclic GMP...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0470
更新日期:1997-09-01 00:00:00
abstract::The Ca(2+) dependent interaction between troponin I (cTnI) and troponin C (cTnC) triggers contraction in heart muscle. Heart failure is characterized by a decrease in cardiac output, and compounds that increase the sensitivity of cardiac muscle to Ca(2+) have therapeutic potential. The Ca(2+)-sensitizer, levosimendan,...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.08.019
更新日期:2010-12-01 00:00:00
abstract::Fibroblast growth factor-2 (FGF-2), administered to the isolated rat heart by perfusion and under constant pressure, is protective against ischemia-reperfusion (I-R). Here we have investigated whether FGF-2 cardioprotection: (a) is dependent on flow modulation; (b) is linked to effects on contractility; (c) is mediate...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0832
更新日期:1998-12-01 00:00:00
abstract::We previously established a new measuring method of the myocardial O2 consumption of mechanically unloaded rat left-ventricular slices. O 2 consumption of unstimulated myocardium corresponds to basal metabolism. We have found O2 consumption of stimulated myocardium to include basal metabolism and O 2 consumption for C...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0630
更新日期:1998-03-01 00:00:00
abstract::beta(1)integrin-deficient (beta(1)-/-) ES cells showed increased differentiation of cardiac cells characterized by reduced adhesion and high beating frequency. Whereas in whole embryoid body outgrowths of beta(1)-/- cells maximum levels of alpha(v), beta(3)and beta(5)integrin mRNA were delayed and transiently upregula...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2000.1326
更新日期:2001-03-01 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::Preconditioning of hearts with the α(1)-adrenoceptor agonist phenylephrine decreases infarct size and increases the functional recovery of the heart following ischaemia-reperfusion. However, the cellular mechanisms responsible for this protection are not known. We investigated the role of protein kinase C ε and δ (PKC...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2011.06.015
更新日期:2011-09-01 00:00:00
abstract::The protection of ischemic preconditioning (PC) appears to be triggered by activation of receptors which couple to protein kinase C (PKC) during the brief ischemia. Previous experiments, however, suggest that phosphorylation of PKC's substrates is not required for the myocytes to enter the preconditioned state. Becaus...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0344
更新日期:1997-03-01 00:00:00
abstract::Under normal physiological conditions atrial natriuretic factor (ANF) in rat is stored in secretory granules in fetal and adult atrial cardiomyocytes (Cantin et al., 1984; de Bold, 1985), whereas in fetal and neonatal ventricular cardiomyocytes secretory granules are practically absent and ANF is directly secreted via...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1993.1088
更新日期:1993-07-01 00:00:00
abstract::In mammalian species, including man, the duration of myocardial contraction is shorter in atria than ventricles. Total contraction time depends at least in part on phosphorylation and dephosphorylation of cardiac regulatory proteins. Dephosphorylation reactions are mediated by protein phosphatases. In the mammalian he...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2000.1265
更新日期:2000-12-01 00:00:00
abstract::Left ventricular pressure overload will result in the hypertrophic growth of the myocardium and in the rat may include a remodeling of both the structural and contractile proteins. As a result, an adaptive rise in active stiffness, or the force generating capacity of the myocardium, may occur. The relative importance ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(88)90597-4
更新日期:1988-12-01 00:00:00
abstract::Aquaporins (AQPs) are a family of water channel proteins that assist in maintenance of the cellular osmotic environment and whole body fluid balance. Specialized organ-specific AQPs are important in physiologic and pathologic processes but little is known about AQPs in the human heart. AQP1 has been identified in rode...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.01.009
更新日期:2004-05-01 00:00:00
abstract::Cell therapy to prevent cardiac dysfunction after myocardial infarction (MI) is less effective in aged patients because aged cells have decreased regenerative capacity. Allogeneic transplanted stem cells (SCs) from young donors are usually rejected. Maintaining transplanted SC immunoprivilege may dramatically improve ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.04.019
更新日期:2015-07-01 00:00:00
abstract::Atrial fibrillation (AF) causes myocyte stress by inducing structural changes, predominantly myolysis, which is related to the progression of AF. As heat shock proteins (Hsp) protect against cellular stress, their efficacy in preventing myolysis was investigated in a tachy-paced cell model for AF and in patients with ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.06.068
更新日期:2006-09-01 00:00:00
abstract::Elevation of cytosolic sodium is thought to be correlated with an increase in force of contraction due to an activation of sodium-calcium exchange. We investigated the inotropic response mediated by the new sodium-channel activator BDF 9148 (0.01-100 mumol/l) on failing human myocardium. Force of contraction was studi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(91)90170-q
更新日期:1991-04-01 00:00:00
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::The loss of cardiomyocytes by apoptosis and the subsequent replacement by fibrous connective tissues are important features of cardiac remodeling in adult heart disease. In children with CHD, however, the cellular and molecular mechanisms of heart failure have not yet been fully understood because of the anatomical an...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.05.011
更新日期:2007-09-01 00:00:00
abstract::The dynamics of the changes in myocardial phosphorylated compound contents (inorganic phosphate: Pi; phosphocreatine: PCr; ATP) induced by 10(-6)M isoprenaline administration was studied, using 31P-NMR spectroscopy, in hearts isolated from rats adapted for three weeks to normobaric hypoxia (10% of oxygen). When compar...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(95)90755-6
更新日期:1995-08-01 00:00:00
abstract::The resting potential of "sodium-loaded' cardiac cells can transiently hyperpolarize to levels negative to the steady state resting potential [3,5,6]. Hyperpolarization is associated with the coupled efflux of Na+ and influx of K+ driven by an active transport process and may result from an increased K+ equilibrium po...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(84)80660-4
更新日期:1984-08-01 00:00:00
abstract:BACKGROUND:Cardiac injury, as measured by troponin elevation, has been reported among hospitalized coronavirus disease 2019 (COVID-19) patients and portends a poor prognosis. However, how the dynamics of troponin elevation interplay with inflammation and coagulation biomarkers over time is unknown. We assessed longitud...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.08.008
更新日期:2020-10-01 00:00:00
abstract::We have demonstrated that scar formation after myocardial infarction (MI) is associated with an endogenous pool of CD44(pos)CD45(neg) multipotential mesenchymal stem cells (MSC). MSC differentiate into fibroblasts secreting collagen that forms a scar and mature into myofibroblasts that express alpha smooth muscle acti...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2013.07.005
更新日期:2013-10-01 00:00:00
abstract::To investigate the interaction of cytoskeleton with the receptor modulation of ionic currents, we studied the effect of muscarinic and beta-adrenergic stimulation in adult guinea-pig ventricular cardiac myocytes treated with paclitaxel and colchicine, two drugs that respectively stabilize or destabilize microtubules. ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(02)00312-7
更新日期:2003-02-01 00:00:00
abstract::Cardioprotection and preconditioning mediated via G-protein-coupled receptors may be lost or impaired with advancing age, limiting ischemic tolerance and the ability to pharmacologically protect older hearts from ischemic injury. Our preliminary findings indicated a loss of delta-opioid receptor-mediated protection in...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.02.011
更新日期:2007-05-01 00:00:00
abstract::Functional studies of different human cell types have been successfully conducted under in vitro conditions. Despite many efforts, it has not been possible to develop a human myocardial preparation in which contractile function can be studied over several days. We hypothesize that by mimicking the in vivo situation in...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.0978
更新日期:1999-08-01 00:00:00
abstract::Densitometric scanning of SDS-polyacrylamide gels was used to measure myosin heavy chain concentration in left ventricular specimens obtained from cat hearts 3 to 12 months after healing of small experimental myocardial infarctions. The study was designed to test the hypothesis that myosin concentration varies as a fu...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(84)80642-2
更新日期:1984-06-01 00:00:00