Functional role of c-Src in gap junctions of the cardiomyopathic heart.

Abstract:

:Given the essential role played by gap junctions in the coordination of cardiac muscle contraction, it is plausible that down-regulation of gap junctional conduction is in part responsible for the contractile dysfunction observed in hypertrophied and failing hearts. In the present study, we analyzed the expression and function of the gap junction protein, connexin43, in the ventricular myocardium of hereditary cardiomyopathic, Syrian BIO 14.6 hamsters. Immunoprecipitation and immunoblot analyses revealed that levels of tyrosine phosphorylated connexin43 were increased in BIO 14.6 hamsters at the late stage of congestive heart failure. Furthermore, the increased tyrosine phosphorylation was correlated with increased c-Src activity. The functional consequences of tyrosine phosphorylation of connexin43 in gap junction were assessed using transfected cells expressing constitutively active c-Src. It was found that constitutively active c-Src diminished propagation of Ca(2+) waves in HEK293 cells and reduced gap junctional conductance between pairs of cardiac myocytes. We, therefore, conclude that during the progression of cardiac dysfunction in the cardiomyopathic heart, gap junctional communication is reduced via c-Src-mediated tyrosine phosphorylation of connexin43.

journal_name

Circ Res

journal_title

Circulation research

authors

Toyofuku T,Yabuki M,Otsu K,Kuzuya T,Tada M,Hori M

doi

10.1161/01.res.85.8.672

subject

Has Abstract

pub_date

1999-10-15 00:00:00

pages

672-81

issue

8

eissn

0009-7330

issn

1524-4571

journal_volume

85

pub_type

杂志文章
  • Effects of intense antecedent sympathetic stimulation on sympathetic neurotransmission in the heart.

    abstract::We studied the effects of intense sympathetic stimulation on the chronotropic responses of the heart to subsequent test stimulations of the cardiac autonomic nerves in dogs anesthetized with alpha-chloralose. Such intense sympathetic stimulations (which we refer to as "release stimulations") are known to release neuro...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.72.1.137

    authors: Yang T,Levy MN

    更新日期:1993-01-01 00:00:00

  • Role of nitric oxide, muscarinic receptors, and the ATP-sensitive K+ channel in mediating the effects of acetylcholine to mimic preconditioning in dogs.

    abstract::The aims of the current study were to examine the efficacy of acetylcholine (ACh) to mimic ischemic preconditioning in dogs and to determine the role of nitric oxide (NO), muscarinic receptors, and ATP-sensitive K+ (KATP) channels in mediating its effects. Barbital-anesthetized open-chest dogs were subjected to 60 min...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.73.6.1193

    authors: Yao Z,Gross GJ

    更新日期:1993-12-01 00:00:00

  • Gli3 regulation of myogenesis is necessary for ischemia-induced angiogenesis.

    abstract:RATIONALE:A better understanding of the mechanism underlying skeletal muscle repair is required to develop therapies that promote tissue regeneration in adults. Hedgehog signaling has been shown previously to be involved in myogenesis and angiogenesis: 2 crucial processes for muscle development and regeneration. OBJEC...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.113.301546

    authors: Renault MA,Vandierdonck S,Chapouly C,Yu Y,Qin G,Metras A,Couffinhal T,Losordo DW,Yao Q,Reynaud A,Jaspard-Vinassa B,Belloc I,Desgranges C,Gadeau AP

    更新日期:2013-10-25 00:00:00

  • Genomic Characterization of Endothelial Enhancers Reveals a Multifunctional Role for NR2F2 in Regulation of Arteriovenous Gene Expression.

    abstract:RATIONALE:Significant progress has revealed transcriptional inputs that underlie regulation of artery and vein endothelial cell fates. However, little is known concerning genome-wide regulation of this process. Therefore, such studies are warranted to address this gap. OBJECTIVE:To identify and characterize artery- an...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.119.316075

    authors: Sissaoui S,Yu J,Yan A,Li R,Yukselen O,Kucukural A,Zhu LJ,Lawson ND

    更新日期:2020-03-27 00:00:00

  • Tumor necrosis factor-alpha induces endothelial dysfunction in the prediabetic metabolic syndrome.

    abstract::Inflammation is a condition that underscores many cardiovascular pathologies including endothelial dysfunction, but no link is yet established between the vascular pathology of the metabolic syndrome with a particular inflammatory cytokine. We hypothesized that impairments in coronary endothelial function in the obese...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000229685.37402.80

    authors: Picchi A,Gao X,Belmadani S,Potter BJ,Focardi M,Chilian WM,Zhang C

    更新日期:2006-07-07 00:00:00

  • Heparin disrupts the CXCR4/SDF-1 axis and impairs the functional capacity of bone marrow-derived mononuclear cells used for cardiovascular repair.

    abstract:RATIONALE:Cell therapy is a promising option for the treatment of acute or chronic myocardial ischemia. The intracoronary infusion of cells imposes the potential risk of cell clotting, which may be prevented by the addition of anticoagulants. However, a comprehensive analysis of the effects of anticoagulants on the fun...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.112.265678

    authors: Seeger FH,Rasper T,Fischer A,Muhly-Reinholz M,Hergenreider E,Leistner DM,Sommer K,Manavski Y,Henschler R,Chavakis E,Assmus B,Zeiher AM,Dimmeler S

    更新日期:2012-09-14 00:00:00

  • Matrix metalloproteinase-3 genotype contributes to age-related aortic stiffening through modulation of gene and protein expression.

    abstract::Matrix metalloproteinases (MMPs) include most major constituents of the arterial wall as substrates. A common promotor polymorphism (5A/6A) is associated with differences in MMP-3 (stromelysin-1) activity, and associations with certain forms of vascular disease have been shown. This study investigated whether the MMP-...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000076891.24317.CA

    authors: Medley TL,Kingwell BA,Gatzka CD,Pillay P,Cole TJ

    更新日期:2003-06-13 00:00:00

  • C-terminal truncation of cardiac troponin I causes divergent effects on ATPase and force: implications for the pathophysiology of myocardial stunning.

    abstract::Myocardial stunning is a form of reversible myocardial ischemia/reperfusion injury associated with systolic and diastolic contractile dysfunction. In the isolated rat heart model, myocardial stunning is characterized by specific C-terminal proteolysis of the myofilament protein, troponin I (cTnI) that yields cTnI1-193...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000099889.35340.6F

    authors: Foster DB,Noguchi T,VanBuren P,Murphy AM,Van Eyk JE

    更新日期:2003-11-14 00:00:00

  • Inducible nitric oxide synthase deficiency protects the heart from systolic overload-induced ventricular hypertrophy and congestive heart failure.

    abstract::Inducible nitric oxide synthase (iNOS) protein is expressed in cardiac myocytes of patients and experimental animals with congestive heart failure (CHF). Here we show that iNOS expression plays a role in pressure overload-induced myocardial chamber dilation and hypertrophy. In wild-type mice, chronic transverse aortic...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000264081.78659.45

    authors: Zhang P,Xu X,Hu X,van Deel ED,Zhu G,Chen Y

    更新日期:2007-04-13 00:00:00

  • Knockout mice for pharmacological screening: testing the specificity of Na+-Ca2+ exchange inhibitors.

    abstract::The role of the Na+-Ca2+ exchanger as a major determinant of cell Ca2+ is well defined in cardiac tissue, and there has been much effort to develop specific inhibitors of the exchanger. We use a novel system to test the specificity of two putative specific inhibitors, KB-R7943 and SEA0400. The drugs are applied to ele...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.0000027529.37429.38

    authors: Reuter H,Henderson SA,Han T,Matsuda T,Baba A,Ross RS,Goldhaber JI,Philipson KD

    更新日期:2002-07-26 00:00:00

  • Intestinal microvascular growth during maturation in diabetic juvenile rats.

    abstract::To determine if intestinal microvascular growth is impaired in diabetic juvenile animals, a segment of the terminal ileum was marked and the microvasculature of this segment observed at the age of 5 weeks and again at the age of 10-11 weeks in normal and diabetic Sprague Dawley rats. Diabetes was induced by streptozot...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.63.2.429

    authors: Unthank JL,Bohlen HG

    更新日期:1988-08-01 00:00:00

  • Cardiac Stem Cell Hybrids Enhance Myocardial Repair.

    abstract:RATIONALE:Dual cell transplantation of cardiac progenitor cells (CPCs) and mesenchymal stem cells (MSCs) after infarction improves myocardial repair and performance in large animal models relative to delivery of either cell population. OBJECTIVE:To demonstrate that CardioChimeras (CCs) formed by fusion between CPCs an...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.115.306838

    authors: Quijada P,Salunga HT,Hariharan N,Cubillo JD,El-Sayed FG,Moshref M,Bala KM,Emathinger JM,De La Torre A,Ormachea L,Alvarez R Jr,Gude NA,Sussman MA

    更新日期:2015-09-25 00:00:00

  • Lymphatic pumping in response to changes in transmural pressure is modulated by erythrolysate/hemoglobin.

    abstract::Red blood cells and lysate products (erythrolysate) are observed consistently in lymph draining acute and chronic inflammatory reactions and from tissues subjected to trauma or surgical procedures. Using hemoglobin as a marker for erythrolysate, we have measured hemoglobin in lymph up to the 10(-6) M range in a number...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.67.5.1097

    authors: Elias RM,Wandolo G,Ranadive NS,Eisenhoffer J,Johnston MG

    更新日期:1990-11-01 00:00:00

  • Effect of superoxide dismutase on myocardial infarct size in the canine heart after 6 hours of regional ischemia and reperfusion: a demonstration of myocardial salvage.

    abstract::Available data demonstrate that oxygen free radicals and derived reactive species of oxygen are produced during myocardial ischemia as well as upon reperfusion of the ischemic tissue. The present study was designed to determine if polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), with its extended plasma ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.64.4.665

    authors: Chi LG,Tamura Y,Hoff PT,Macha M,Gallagher KP,Schork MA,Lucchesi BR

    更新日期:1989-04-01 00:00:00

  • Sodium pump inhibition, enhanced calcium influx via sodium-calcium exchange, and positive inotropic response in cultured heart cells.

    abstract::The effects of sodium pump inhibition produced by exposure to the cardiac glycosides, ouabain or dihydroouabain, or by reduction in extracellular potassium to 1.0 mM, on contractile state and sodium-calcium exchange were studied in primary monolayer cultures of chick embryo ventricular cells. Ouabain, 10(-6)M, dihydro...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.56.2.231

    authors: Barry WH,Hasin Y,Smith TW

    更新日期:1985-02-01 00:00:00

  • Nuclear targeting of Akt enhances kinase activity and survival of cardiomyocytes.

    abstract::Heart failure is associated with death of cardiomyocytes leading to loss of contractility. Previous studies using membrane-targeted Akt (myristolated-Akt), an enzyme involved in antiapoptotic signaling, showed inhibition of cell death and prevention of pathogenesis induced by cardiomyopathic stimuli. However, recent s...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000124394.01180.BE

    authors: Shiraishi I,Melendez J,Ahn Y,Skavdahl M,Murphy E,Welch S,Schaefer E,Walsh K,Rosenzweig A,Torella D,Nurzynska D,Kajstura J,Leri A,Anversa P,Sussman MA

    更新日期:2004-04-16 00:00:00

  • Thrombospondin-4 is required for stretch-mediated contractility augmentation in cardiac muscle.

    abstract:RATIONALE:One of the physiological mechanisms by which the heart adapts to a rise in blood pressure is by augmenting myocyte stretch-mediated intracellular calcium, with a subsequent increase in contractility. This slow force response was first described over a century ago and has long been considered compensatory, but...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.111.256743

    authors: Cingolani OH,Kirk JA,Seo K,Koitabashi N,Lee DI,Ramirez-Correa G,Bedja D,Barth AS,Moens AL,Kass DA

    更新日期:2011-12-09 00:00:00

  • Stroke Caused by Atherosclerosis of the Major Intracranial Arteries.

    abstract::Our goal in this review is to discuss the pathophysiology, diagnosis, and treatment of stroke caused by atherosclerosis of the major intracranial arteries. References for the review were identified by searching PubMed for related studies published from 1955 to June 2016 using search terms intracranial stenosis and int...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.116.308441

    authors: Banerjee C,Chimowitz MI

    更新日期:2017-02-03 00:00:00

  • Ca(2+) signaling in cardiac myocytes overexpressing the alpha(1) subunit of L-type Ca(2+) channel.

    abstract::Voltage-gated L-type Ca(2+) channels (LCCs) provide Ca(2+) ingress into cardiac myocytes and play a key role in intracellular Ca(2+) homeostasis and excitation-contraction coupling. We investigated the effects of a constitutive increase of LCC density on Ca(2+) signaling in ventricular myocytes from 4-month-old transg...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/hh0202.103230

    authors: Song LS,Guia A,Muth JN,Rubio M,Wang SQ,Xiao RP,Josephson IR,Lakatta EG,Schwartz A,Cheng H

    更新日期:2002-02-08 00:00:00

  • Sarco/endoplasmic reticulum Ca2+-ATPase gene transfer reduces vascular smooth muscle cell proliferation and neointima formation in the rat.

    abstract::Proliferation of vascular smooth muscle cells (VSMC) is a primary cause of vascular disorders and is associated with major alterations in Ca2+ handling supported by loss of the sarco/endoplasmic reticulum calcium ATPase, SERCA2a. To determine the importance of SERCA2a in neointima formation, we have prevented loss of ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000180663.42594.aa

    authors: Lipskaia L,del Monte F,Capiod T,Yacoubi S,Hadri L,Hours M,Hajjar RJ,Lompré AM

    更新日期:2005-09-02 00:00:00

  • Nitric oxide donors induce late preconditioning against myocardial stunning and infarction in conscious rabbits via an antioxidant-sensitive mechanism.

    abstract::The goal of this study was to test the hypothesis that the cardioprotective effects of the late phase of ischemic preconditioning (PC) can be mimicked by treatment with NO donors. In phase I (studies of myocardial stunning), conscious rabbits underwent a sequence of six 4-minute coronary occlusion/4-minute reperfusion...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.83.1.73

    authors: Takano H,Tang XL,Qiu Y,Guo Y,French BA,Bolli R

    更新日期:1998-07-13 00:00:00

  • Mitogenic effect of angiotensin II on rat carotid arteries and type II or III mesenteric microvessels but not type I mesenteric microvessels is mediated by endogenous basic fibroblast growth factor.

    abstract::In this study, anti-basic fibroblast growth factor (anti-bFGF) antibody was used to determine whether the mitogenic effect of angiotensin II in vivo could be blocked by neutralizing bFGF in the vessel wall. Animals, divided into six experimental groups, were given (1) angiotensin II, (2) angiotensin II + anti-bFGF ant...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.res.82.3.321

    authors: Su EJ,Lombardi DM,Wiener J,Daemen MJ,Reidy MA,Schwartz SM

    更新日期:1998-02-23 00:00:00

  • Receptor-interacting protein kinase 3 contributes to abdominal aortic aneurysms via smooth muscle cell necrosis and inflammation.

    abstract:RATIONALE:Depletion of medial smooth muscle cell (SMC) is a major pathological characteristic of abdominal aortic aneurysm (AAA), although the mechanism by which these cells are eliminated remains incompletely understood. We reasoned that necroptosis, a recently described form of necrosis mediated by receptor-interacti...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.116.304899

    authors: Wang Q,Liu Z,Ren J,Morgan S,Assa C,Liu B

    更新日期:2015-02-13 00:00:00

  • Interleukin-1 beta inhibits phospholamban gene expression in cultured cardiomyocytes.

    abstract::Phospholamban is a key regulatory protein that defines diastolic function. Proinflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) can depress contractility and intracellular Ca2+ currents and transients. An alteration in phospholamban expression is a possible pathway by wh...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.81.4.493

    authors: McTiernan CF,Lemster BH,Frye C,Brooks S,Combes A,Feldman AM

    更新日期:1997-10-01 00:00:00

  • Blood pressure and vascular resistance in genetically hypertensive rats treated at birth with 6-hydroxydopamine.

    abstract::Genetically hypertensive (GH) rats of the New Zealand strain and normotensive (N) rats were sympathectomized from birth with 6-hydroxydopamine (100 mg/kg,s.c, on alternate days, seven treatments). In adult treated rats from each strain (GHTr and NTr), blood pressure was lower than normal. Functional tests and electron...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.43.2.293

    authors: Clark DW,Jones DR,Phelan EL,Devine CE

    更新日期:1978-08-01 00:00:00

  • Elevated homocysteine reduces apolipoprotein A-I expression in hyperhomocysteinemic mice and in males with coronary artery disease.

    abstract::Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by nutritional or genetic disturbances in homocysteine metabolism. A polymorphism in methylenetetrahydrofolate reductase (MTHFR) is the most common genetic cause of mild hyperhomocysteinemia. To examine mechanisms by which an elevation in plasma...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000204825.66410.0b

    authors: Mikael LG,Genest J Jr,Rozen R

    更新日期:2006-03-03 00:00:00

  • Changes in mitochondrial DNA in cardiac hypertrophy in the rat.

    abstract::We studied DNA (mtDNA) replication in adult female rat hearts undergoing hypertrophy secondary to constriction of the ascending aorta. MtDNA was measured in isolated mitochondria by a fluorometric method adapted for that purpose. The conditions for removal of contaminating nuclear DNA were developed, and the purity of...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.45.4.505

    authors: Rajamanickam C,Merten S,Kwiatkowska-Patzer B,Chuang CH,Zak R,Rabinowitz M

    更新日期:1979-10-01 00:00:00

  • Exacerbation of chronic renovascular hypertension and acute renal failure in heme oxygenase-1-deficient mice.

    abstract::Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Because of properties of HO and its products, we hypothesi...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/hh1001.091521

    authors: Wiesel P,Patel AP,Carvajal IM,Wang ZY,Pellacani A,Maemura K,DiFonzo N,Rennke HG,Layne MD,Yet SF,Lee ME,Perrella MA

    更新日期:2001-05-25 00:00:00

  • Increased myogenic tone and diminished responsiveness to ATP-sensitive K+ channel openers in cerebral arteries from diabetic rats.

    abstract::Diabetes mellitus has profound adverse effects on vascular and, in particular, endothelial function. Although pressure-induced constriction ("myogenic tone") is a major contributor to the regulation of blood flow, little is known about the effects of diabetes on this response. Diabetes has been shown to diminish the d...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.81.6.996

    authors: Zimmermann PA,Knot HJ,Stevenson AS,Nelson MT

    更新日期:1997-12-01 00:00:00

  • Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apolipoprotein A-I Protein synthesis and enhancing HDL cholesterol clearance.

    abstract::We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine beta-synthase-/apolipoprotein E-deficient (CBS(-/-)/apoE(-/-)) mice. We o...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000242559.42077.22

    authors: Liao D,Tan H,Hui R,Li Z,Jiang X,Gaubatz J,Yang F,Durante W,Chan L,Schafer AI,Pownall HJ,Yang X,Wang H

    更新日期:2006-09-15 00:00:00