Abstract：
:Serine/threonine protein phosphatases control dephosphorylation of numerous cardiac proteins, including a variety of ion channels and calcium-handling proteins, thereby providing precise post-translational regulation of cardiac electrophysiology and function. Accordingly, dysfunction of this regulation can contribute to the initiation, maintenance and progression of cardiac arrhythmias. Atrial fibrillation (AF) is the most common heart rhythm disorder and is characterized by electrical, autonomic, calcium-handling, contractile, and structural remodeling, which include, among other things, changes in the phosphorylation status of a wide range of proteins. Here, we review AF-associated alterations in the phosphorylation of atrial ion channels, calcium-handling and contractile proteins, and their role in AF-pathophysiology. We highlight the mechanisms controlling the phosphorylation of these proteins and focus on the role of altered dephosphorylation via local type-1, type-2A and type-2B phosphatases (PP1, PP2A, and PP2B, also known as calcineurin, respectively). Finally, we discuss the challenges for phosphatase research, potential therapeutic significance of altered phosphatase-mediated protein dephosphorylation in AF, as well as future directions.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Heijman J,Ghezelbash S,Wehrens XH,Dobrev Ddoi
10.1016/j.yjmcc.2016.12.009subject
Has Abstractpub_date
2017-02-01 00:00:00pages
110-120eissn
0022-2828issn
1095-8584pii
S0022-2828(16)30451-5journal_volume
103pub_type
杂志文章,评审abstract：:Ischemic preconditioning reduces infarct size and improves cardiac function in various species, including mice. The mechanism for ischemic preconditioning protection is not entirely clear and activation of alpha(1B)-adrenergic receptors (AR) is believed to be involved. Transgenic mice expressing constitutively active ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2000.1201
更新日期：2000-09-01 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：:Brain renin-angiotensin system (RAS) hyperactivity has been implicated in sympathetic hyperactivity and progressive left ventricular (LV) dysfunction after myocardial infarction (MI). Angiotensin III, generated by aminopeptidase A (APA), is one of the main effector peptides of the brain RAS in the control of cardiac f...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2018.12.008
更新日期：2019-02-01 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：:Elevation of intracellular cAMP concentration has numerous vascular protective effects that are in part mediated via actin cytoskeleton-remodelling and subsequent regulation of gene expression. However, the mechanisms are incompletely understood. Here we investigated whether cAMP-induced actin-cytoskeleton remodelling...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2014.11.012
更新日期：2015-02-01 00:00:00
abstract：:Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative condition with a heterogeneous cardiac phenotype caused primarily by an expanded GAA trinucleotide repeat in the frataxin gene (FXN). FXN is important in mitochondrial iron efflux, sensitivity to oxidative stress, and cell death. The number of GAA re...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2011.07.001
更新日期：2011-11-01 00:00:00
abstract：:Although protection against necrosis has been observed in both hibernating (HIB) and ischemic preconditioned hearts in the second window of protection (SWOP), a comparison of the mitochondrial proteome between the two entities has not been previously performed. Anesthetized swine underwent instrumentation with a fixed...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2013.03.018
更新日期：2013-07-01 00:00:00
abstract：BACKGROUND:Heat shock proteins (hsp) constitute an endogenous stress response that protects cells from injury. Most work on these important proteins has focused on the immediate response to acute stress in cell culture systems and mammalian models of heart disease. Little is known about the expression of the hsps in hu...
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：:Angiotensin II has been shown to be mitogenic in various cell types. In cultured neonatal cardiomyocytes, we have demonstrated that angiotensin II causes hypertrophy, not hyperplasia. However, fetal or neonatal cardiomyocytes exhibit limited proliferation in primary culture, and are mitotically less potent. In order t...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0770
更新日期：1998-10-01 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：:Although cardiac failure can develop over time after myocardial infarction, the mechanism responsible for this is still unknown. The change of intracellular Ca2+ transport protein, such as sarcoplasmic reticulum (SR) Ca2+-ATPase (SR-Ca2+), Na+-Ca2+ exchanger (Na+-Ca2+), or cardiac phenotypic modulation of contractile ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1996.0270
更新日期：1997-01-01 00:00:00
abstract：:Diastolic dysfunction in the aging heart is a grave condition that challenges the life and lifestyle of a growing segment of our population. This report seeks to examine the role and interrelationship of inflammatory dysregulation in interstitial myocardial fibrosis and progressive diastolic dysfunction in aging mice....
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2010.10.019
更新日期：2011-01-01 00:00:00
abstract：:Calmodulin (CaM) is a Ca-binding protein that binds to, and can directly inhibit cardiac ryanodine receptor calcium release channels (RyR2). Animal studies have shown that RyR2 hyperphosphorylation reduces CaM binding to RyR2 in failing hearts, but data are lacking on how CaM regulates human RyR2 and how this regulati...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2019.03.018
更新日期：2019-05-01 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：:Local signaling domains and numerous interacting molecular pathways and substrates contribute to the whole-cell response of myocytes during β-adrenergic stimulation (βARS). We aimed to elucidate the quantitative contribution of substrates and their local signaling environments during βARS to the canine epicardial vent...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2011.02.007
更新日期：2011-05-01 00:00:00
abstract：:Doxorubicin (DOX)-induced cardiotoxicity has been a well-known phenomenon to clinicians and scientists for decades; however, molecular mechanisms underlying DOX cardiotoxicity are still being uncovered. Although the majority of prior research have implicated nuclear and mitochondrial events to be an important etiologi...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2017.01.007
更新日期：2017-03-01 00:00:00
abstract：:In essential hypertension it has been hypothesized that there is a generalized derangement in cellular Ca2+ homeostasis. The aim of this study was to assess whether there is functional evidence for increased vulnerability to Ca overload in cardiomyocytes derived from age-matched (11-week) normotensive Wistar-Kyoto (WK...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1996.0067
更新日期：1996-04-01 00:00:00
abstract：:The kappa-opioid receptor exerts a negative modulatory action on the beta-adrenoceptor and the action is blunted in adult spontaneously hypertensive rats (SHR). In order to determine whether the blunted negative modulation of the beta-adrenoceptor by the kappa-opioid receptor contributes to the development of hyperten...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0896
更新日期：1999-03-01 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：:The transcription factor Nuclear Factor Kappa B (NF-κB) has been shown to be cardioprotective after permanent coronary occlusion (PO) and late ischemic preconditioning (IPC), and yet it is cell injurious after ischemia/reperfusion (I/R) in the heart. There is limited information regarding NF-κB-dependent cardioprotect...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2011.03.011
更新日期：2011-07-01 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：:Little is known about the tissue-specific expression of contractile proteins during cardiogenesis in the mammalian heart. Since the myosin heavy chain (HC) isoform expressed in the adult correlates with myocardial functional capacity, we undertook an analysis of myosin HC expression in atrial and ventricular myocardia...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(90)91469-n
更新日期：1990-03-01 00:00:00
abstract：:Recent work has highlighted the role of NR4A receptors in atherosclerosis and inflammation. In vascular smooth muscle cell (VSMC) proliferation, however, NOR-1 (neuron-derived orphan receptor-1) exerts antagonistic effects to Nur77 and Nurr1. The aim of this study was to analyse the effect of NOR-1 in VSMC inflammator...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2014.12.015
更新日期：2015-03-01 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：: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：:The importance of endogenous and exogenous estrogen levels to the development of cardiovascular disease in women in controversial. The purpose of our study was to examine the effect of estrogen on the development of hypertension, cardiac hypertrophy, ventricular function, and gene expression for atrial natriuretic pep...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1999.0985
更新日期：1999-08-01 00:00:00
abstract：:We compared myocardial mechanics and myosin isozymes of right and left ventricular papillary muscles from adult (6 to 8 month old) male rats. Analysis of force velocity relations indicate that right ventricular papillary muscles contract more rapidly than left at light loads (2.68 +/- 0.13 vs 2.18 +/- 0.07 muscle leng...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(87)80395-4
更新日期：1987-05-01 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：:Ischemic tolerance decreases with aging and the cardioprotective effect of ischemic preconditioning (IPC) is impaired in aged animals. Although lifelong caloric restriction (CR) profoundly affects the physiological and pathophysiological modifications induced by aging and markedly increases life span in several specie...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2005.03.010
更新日期：2005-08-01 00:00:00
abstract：:We hypothesized that chronic xanthine oxidase inhibition (XOI) would have favorable effects on both ventricular and vascular performance in evolving heart failure (HF), thereby preserving ventricular-vascular coupling. In HF, XOI reduces oxidative stress and improves both vascular and myocardial function. Dogs were ra...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2005.04.008
更新日期：2005-09-01 00:00:00
