Abstract:
AIMS:The cAMP-dependent protein kinase (PKA) mediates β-adrenoceptor (β-AR) regulation of cardiac contraction and gene expression. Whereas PKA activity is well characterized in various subcellular compartments of adult cardiomyocytes, its regulation in the nucleus remains largely unknown. The aim of the present study was to compare the modalities of PKA regulation in the cytoplasm and nucleus of cardiomyocytes. METHODS AND RESULTS:Cytoplasmic and nuclear cAMP and PKA activity were measured with targeted fluorescence resonance energy transfer probes in adult rat ventricular myocytes. β-AR stimulation with isoprenaline (Iso) led to fast cAMP elevation in both compartments, whereas PKA activity was fast in the cytoplasm but markedly slower in the nucleus. Iso was also more potent and efficient in activating cytoplasmic than nuclear PKA. Similar slow kinetics of nuclear PKA activation was observed upon adenylyl cyclase activation with L-858051 or phosphodiesterase (PDE) inhibition with 3-isobutyl-1-methylxantine. Consistently, pulse stimulation with Iso (15 s) maximally induced PKA and myosin-binding protein C phosphorylation in the cytoplasm, but marginally activated PKA and cAMP response element-binding protein phosphorylation in the nucleus. Inhibition of PDE4 or ablation of the Pde4d gene in mice prolonged cytoplasmic PKA activation and enhanced nuclear PKA responses. In the cytoplasm, phosphatase 1 (PP1) and 2A (PP2A) contributed to the termination of PKA responses, whereas only PP1 played a role in the nucleus. CONCLUSION:Our study reveals a differential integration of cytoplasmic and nuclear PKA responses to β-AR stimulation in cardiac myocytes. This may have important implications in the physiological and pathological hypertrophic response to β-AR stimulation.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Haj Slimane Z,Bedioune I,Lechêne P,Varin A,Lefebvre F,Mateo P,Domergue-Dupont V,Dewenter M,Richter W,Conti M,El-Armouche A,Zhang J,Fischmeister R,Vandecasteele Gdoi
10.1093/cvr/cvu029subject
Has Abstractpub_date
2014-04-01 00:00:00pages
97-106issue
1eissn
0008-6363issn
1755-3245pii
cvu029journal_volume
102pub_type
杂志文章abstract:OBJECTIVE:The aim was to determine the relationship between the rate of reflow and vulnerability to reperfusion induced arrhythmias. METHODS:Isolated rat hearts, in which left and right coronary arteries were perfused independently, were subjected to transient (10 min) cessation of flow to the left coronary bed. Durin...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.4.316
更新日期:1992-04-01 00:00:00
abstract:AIMS:The molecular mechanisms controlling heart function and rhythmicity are incompletely understood. While it is widely accepted that the type 2 ryanodine receptor (Ryr2) is the major Ca(2+) release channel in excitation-contraction coupling, the role of these channels in setting a consistent beating rate remains cont...
journal_title:Cardiovascular research
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doi:10.1093/cvr/cvs260
更新日期:2012-12-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.7.980
更新日期:1994-07-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.07.012
更新日期:2007-12-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
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更新日期:2000-09-01 00:00:00
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journal_title:Cardiovascular research
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doi:10.1016/s0008-6363(03)00353-5
更新日期:2003-07-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu249
更新日期:2015-02-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp230
更新日期:2009-12-01 00:00:00
abstract::Arterial blood pressures were measured simultaneously in the thoracic and abdominal aortas in the same conscious rats. Intravenous administration of sodium nitroprusside caused a greater fall in systolic blood pressure in the abdominal aorta than in the thoracic aorta, whereas intravenous administration of methoxamine...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.5.379
更新日期:1986-05-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.02.005
更新日期:2006-06-01 00:00:00
abstract:OBJECTIVES:Angiotensin converting enzyme (ACE) activity in the plasma does not change significantly with hypertension in two-kidney, one-clip hypertensive (2K-1C) rats. However, heart ACE activity and mRNA increase with hypertension. We measured the ACE activity and mRNA in hypertrophied hearts at different times after...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::Since data on velocity fields in the ascending aorta downstream of normal aortic valves in pigs have not yet been obtained velocity profiles were visualised using a hot film anemometer needle probe before and after total cardiopulmonary bypass and cold cardioplegic arrest. Furthermore, measurements were made during in...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.7.464
更新日期:1988-07-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00149-2
更新日期:1999-08-15 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
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更新日期:2020-01-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.3.312
更新日期:1994-03-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu123
更新日期:2014-07-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs250
更新日期:2012-11-01 00:00:00
abstract::Computation of indices of regional myocardial contractility such as the shortening, or the work done by or on a segment of myocardium in a single cardial cycle is tedious to perform manually, and complex interfacing and software is needed for digital computation. We describe the principles of an on-line, analogue devi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.12.767
更新日期:1983-12-01 00:00:00
abstract::The effects of adrenaline on kinetically-distinct compartments of exchangeable calcium in the spontaneously-beating perfused rat heart were investigated under steady-state conditions using a 45Ca2+ outflow technique together with a nonlinear least-squares curve fitting procedure and 51Cr-EDTA to monitor the loss of fr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.2.88
更新日期:1983-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00269-2
更新日期:2000-01-14 00:00:00
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pub_type: 杂志文章
doi:10.1093/cvr/22.8.537
更新日期:1988-08-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu209
更新日期:2014-11-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy012
更新日期:2018-04-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.5.353
更新日期:1991-05-01 00:00:00
abstract:AIMS:Shock wave therapy (SWT) represents a clinically widely used angiogenic and thus regenerative approach for the treatment of ischaemic heart or limb disease. Despite promising results in preclinical and clinical trials, the exact mechanism of action remains unknown. Toll-like receptor 3, which is part of the innate...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv272
更新日期:2016-02-01 00:00:00
abstract::The left ansa subclavia was stimulated at supramaximal intensity at a frequency of Hz in open-chest, anaesthetized dogs for periods of about 10 min. Arterial blood pressure, myocardial contractile force, and coronary sinus blood flow reached peak values after 1 or 2 min of stimulation, and then declined gradually thro...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/10.5.549
更新日期:1976-09-01 00:00:00
abstract::Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia associated with pronounced morbidity, mortality, and socio-economic burden. This pathological entity is associated with an altered expression profile of genes that are important for atrial function. MicroRNAs (miRNAs), a new class of non-cod...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvq350
更新日期:2011-03-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.6.603
更新日期:1992-06-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvy068
更新日期:2018-07-15 00:00:00