Abstract:
:Regulator of G protein signalling 2 (RGS2) is known to play a protective role in maladaptive cardiac hypertrophy and heart failure via its ability to inhibit Gq- and Gs- mediated GPCR signalling. We previously demonstrated that RGS2 can also inhibit protein translation and can thereby attenuate cell growth. This G protein-independent inhibitory effect has been mapped to a 37 amino acid domain (RGS2eb) within RGS2 that binds to eukaryotic initiation factor 2B (eIF2B). When expressed in neonatal rat cardiomyocytes, RGS2eb attenuates both protein synthesis and hypertrophy induced by Gq- and Gs- activating agents. In the current study, we investigated the potential cardioprotective role of RGS2eb by determining whether RGS2eb transgenic (RGS2eb TG) mice with cardiomyocyte specific overexpression of RGS2eb show resistance to the development of hypertrophy in comparison to wild-type (WT) controls. Using transverse aortic constriction (TAC) in a pressure-overload hypertrophy model, we demonstrated that cardiac hypertrophy was inhibited in RGS2eb TG mice compared to WT controls following four weeks of TAC. Expression of the hypertrophic markers atrial natriuretic peptide (ANP) and β-myosin heavy chain (MHC-β) was also reduced in RGS2eb TG compared to WT TAC animals. Furthermore, cardiac function in RGS2eb TG TAC mice was significantly improved compared to WT TAC mice. Notably, cardiomyocyte cell size was significantly decreased in TG compared to WT TAC mice. These results suggest that RGS2 may limit pathological cardiac hypertrophy at least in part via the function of its eIF2B-binding domain.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Lee KN,Lu X,Nguyen C,Feng Q,Chidiac Pdoi
10.1016/j.yjmcc.2017.06.007subject
Has Abstractpub_date
2017-07-01 00:00:00pages
194-202eissn
0022-2828issn
1095-8584pii
S0022-2828(17)30118-9journal_volume
108pub_type
杂志文章abstract::Hearts from untreated or enalapril-treated piglets were used to measure rates of ribosome formation and total protein synthesis during perfusion as modified Langendorff preparations. Pretreatment of newborn piglets with enalapril maleate (5 mg, once daily for 3 days) resulted in a decreased rate of growth of the left ...
journal_title:Journal of molecular and cellular cardiology
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doi:10.1006/jmcc.1993.1046
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abstract::Cardiac calcium channel activity is markedly increased by beta-adrenergic agents or calcium agonists such as Bay K 8644. The molecular mechanisms underlying these important modulatory effects have been studied with patch clamp techniques by several groups. This paper presents new experiments and reviews published evid...
journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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abstract:AIMS:Ischaemic cardiovascular disease is a major cause of morbidity and mortality worldwide. Despite promising results from pre-clinical animal models, VEGF-based strategies for therapeutic angiogenesis have yet to achieve successful reperfusion of ischaemic tissues in patients. Failure to restore efficient VEGF activi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.07.001
更新日期:2017-08-01 00:00:00
abstract::In the postnatal rat heart, muscle cells continue to divide as well as increase in size. At the same time the cells in the soleus muscle (a slow skeletal muscle) do not divide, although they continue to grow in size. Since microtubules may have a role in orienting intracellular structures in muscle, we determined the ...
journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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doi:10.1016/0022-2828(92)93181-i
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journal_title:Journal of molecular and cellular cardiology
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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:2007-02-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(95)90058-6
更新日期:1995-05-01 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.2000.1136
更新日期:2000-06-01 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.2013.03.018
更新日期:2013-07-01 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.2009.01.015
更新日期:2009-05-01 00:00:00
abstract::Atrial fibrillation (AF) is associated with oxidative stress and Ca2+-handling abnormalities in atrial myocytes. Our prior study has demonstrated the involvement of CD44, a membrane receptor for hyaluronan (HA), in the pathogenesis of AF. This study further evaluated whether CD44 and its related signaling mediate atri...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/s0022-2828(84)80711-7
更新日期:1984-01-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0646
更新日期:1998-04-01 00:00:00
abstract::Cardiac β-adrenergic receptors (β-AR) and Ca2+-Calmodulin dependent protein kinase (CaMKII) regulate both physiological and pathophysiological Ca2+ signaling. Elevated diastolic Ca2+ leak from the sarcoplasmic reticulum (SR) contributes to contractile dysfunction in heart failure and to arrhythmogenesis. β-AR activati...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.04.005
更新日期:2017-07-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(85)80037-7
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80010-4
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.09.003
更新日期:2005-12-01 00:00:00
abstract::Heart failure of diverse causes is associated with abnormalities of sarcoplasmic reticulum (SR) Ca(2+)transport. The purpose of this study was to determine whether the thyroid hormone analogue, 3,5-diiodothyropropionic acid (DITPA), prevents abnormal Ca(2+)transport and expression of SR proteins associated with post-i...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2000.1225
更新日期:2000-11-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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doi:10.1006/jmcc.1996.0316
更新日期:1997-02-01 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.1993.1088
更新日期:1993-07-01 00:00:00
abstract::CD34+ progenitor cells hold promise for therapeutic neovascularization in various settings. In this study, the role of human peripheral blood CD34+ cells in neovascularization and inflammatory cell recruitment was longitudinally studied in vivo. Human CD34+ cells were incorporated in Matrigel, implanted subcutaneously...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.03.907
更新日期:2007-06-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.1087
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abstract::Recently it was shown that lipopolysaccharide (LPS) impairs the pacemaker current in human atrial myocytes. It was speculated that reduced heart rate variability (HRV), typical of patients with severe sepsis, may partially be explained by this impairment. We evaluated the effect of various types of LPS on the activity...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2011.05.004
更新日期:2011-08-01 00:00:00
abstract::Congenital heart block (CHB) affects offspring of mothers with autoantibodies (positive IgG) to intracellular SSA/Ro and SSB/La ribonucleoproteins and is associated with high morbidity and mortality. Here, we show that maternal anti-Ro/La antibodies immunoreact with human fetal cardiomyocyte sarcolemma, recognize huma...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1379
更新日期:2001-06-01 00:00:00
abstract::The heart responds to increased haemodynamic load with growth of the ventricles. The rise in ventricle mass is due to increasing mass of the myocytes and proliferation of fibroblasts and smooth muscle cells. The accompanying adaptation and remodelling of the interstitium, e.g. production and composition of the extrace...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0280
更新日期:1997-01-01 00:00:00