δPKC interaction with the d subunit of F1Fo ATP synthase impairs energetics and exacerbates ischemia/reperfusion injury in isolated rat hearts.


:Previously, we demonstrated protection against hypoxic injury in neonatal cardiac myocytes and reduced release of cardiac troponin I from perfused rat hearts by a novel peptide inhibitor [NH2-YGRKKRRQRRRMLATRALSLIGKRAISTSVCAGRKLALKTIDWVSFDYKDDDDK-] of the delta protein kinase C (δPKC) interaction with the "d" subunit of mitochondrial F1Fo ATP synthase (dF1Fo). This peptide was developed in our laboratory and contains: an HIV-Tat protein transduction domain; a mitochondrial targeting motif; the δPKC-dF1Fo inhibitor sequence; and a FLAG epitope. In the present study the δPKC-dF1Fo inhibitor attenuated co-immunoprecipitation of δPKC with dF1Fo, improved recovery of contractility, diminished levels of tissue t-carbonyls and 4-hydroxy-2-nonenal (HNE), and reduced 2,3,5-triphenyltetrazolium chloride-monitored infarct size following simulated global ischemia/reperfusion (IR) exposures. Perfusion of hearts with this peptide prior to IR enhanced ATP levels 2.1-fold, improved ADP (state 3)- and FCCP (maximal)-stimulated respiration in mitochondrial oxygen consumption assays, and attenuated Ca(++)-induced mitochondrial swelling following ischemic injury. Mitochondrial membrane potential (assessed by JC-1) was also improved 1.6-fold by the inhibitor in hearts subsequently exposed to IR injury. Brief IR exposures did not cause mitochondrial loss of cytochrome c in the presence or absence of the inhibitor. Additionally, the inhibitor did not modify accumulation of the autophagy marker LC3II after brief IR injury. Our results support the potential for this first-in-class peptide as a translational agent for combating cardiac IR injury.


J Mol Cell Cardiol


Walker M,Caldwell RW,Yoon Y,Nguyen TT,Johnson JA




Has Abstract


2015-12-01 00:00:00




Pt B










  • Acetaldehyde dehydrogenase 2 deficiency exacerbates cardiac fibrosis by promoting mobilization and homing of bone marrow fibroblast progenitor cells.

    abstract::Cardiac fibrosis is a common feature of various cardiovascular diseases. Previous studies showed that acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbated pressure overload-induced heart failure. However, the role and mechanisms of cardiac fibrosis in this process remain largely unknown. This study aimed to inv...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Li X,Weng X,Shi H,Gao R,Wang P,Jia D,Zhang S,Dong Z,Sun X,Yang J,Wang Z,Liu R,Li Y,Qiu Z,Hu K,Sun A,Ge J

    更新日期:2019-12-01 00:00:00

  • Mechanisms of action of beta-adrenergic agents on the arrhythmogenic transient inward current in rabbit Purkinje fibers.

    abstract::Catecholamines increase the amplitudes of oscillatory afterpotentials (OAP) and peak magnitude of the transient inward current (Iti) responsible for OAP. The objectives of this study were to determine whether beta-adrenoceptor stimulation can induce Iti, and to determine the mechanism by which beta-adrenoceptor stimul...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Han XQ,Ferrier GR

    更新日期:1991-05-01 00:00:00

  • Heat shock protein upregulation protects against pacing-induced myolysis in HL-1 atrial myocytes and in human atrial fibrillation.

    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


    authors: Brundel BJ,Henning RH,Ke L,van Gelder IC,Crijns HJ,Kampinga HH

    更新日期:2006-09-01 00:00:00

  • Effects of myosin heavy chain manipulation in experimental heart failure.

    abstract::The myosin heavy chain (MHC) isoforms, alpha- and beta-MHC, are expressed in developmental- and chamber-specific patterns. Healthy human ventricle contains approximately 2-10% alpha-MHC and these levels are reduced even further in the failing ventricle. While down-regulation of alpha-MHC in failing myocardium is consi...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: James J,Hor K,Moga MA,Martin LA,Robbins J

    更新日期:2010-05-01 00:00:00

  • β-Adrenergic induced SR Ca2+ leak is mediated by an Epac-NOS pathway.

    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


    authors: Pereira L,Bare DJ,Galice S,Shannon TR,Bers DM

    更新日期:2017-07-01 00:00:00

  • Dysfunction of cardiac ryanodine receptors in the metabolic syndrome.

    abstract::This study examined the hypothesis that the prediabetic metabolic syndrome alters expression, phosphorylation state and binding affinity of cardiac RyR2. Real-time PCR and Western blot analysis were used to assess mRNA and protein expression in the left ventricle, right ventricle and right atrium from control (n=5) an...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Dincer UD,Araiza A,Knudson JD,Shao CH,Bidasee KR,Tune JD

    更新日期:2006-07-01 00:00:00

  • What is the mitochondrial permeability transition pore?

    abstract::Under conditions of mitochondrial calcium overload, especially when accompanied by oxidative stress, elevated phosphate concentrations and adenine nucleotide depletion, a non-specific pore, the mitochondrial permeability transition pore (MPTP), opens in the inner mitochondrial membrane. MPTP opening enables free passa...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审


    authors: Halestrap AP

    更新日期:2009-06-01 00:00:00

  • Detection of TUNEL-positive cardiomyocytes and c-kit-positive progenitor cells in children with congenital heart disease.

    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


    authors: Sato H,Shiraishi I,Takamatsu T,Hamaoka K

    更新日期:2007-09-01 00:00:00

  • Differential roles of cardiac and leukocyte derived macrophage migration inhibitory factor in inflammatory responses and cardiac remodelling post myocardial infarction.

    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


    authors: White DA,Su Y,Kanellakis P,Kiriazis H,Morand EF,Bucala R,Dart AM,Gao XM,Du XJ

    更新日期:2014-04-01 00:00:00

  • Changes in mitochondrial matrix free calcium in perfused rat hearts subjected to hypoxia-reoxygenation.

    abstract::Reperfusion or reoxygenation of ischaemic or hypoxic cardiac tissue results in increases in total cell calcium and cell lysis both of which are dependent on mitochondrial function. Although changes which occur during this period of exposure of the tissue to hypoxia predispose the heart to take up calcium on reoxygenat...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Allen SP,Darley-Usmar VM,McCormack JG,Stone D

    更新日期:1993-08-01 00:00:00

  • Syndecan-4 over-expression preserves cardiac function in a rat model of myocardial infarction.

    abstract::Syndecan-4 (synd4) is a heparan sulfate proteoglycan, involved in repair following tissue damage, through modulating neovascularization and inflammation. In acute myocardial infarction its myocardial expression is up-regulated in a time-dependent manner, and in synd4-deficient mice severe cardiac dysfunction and abnor...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Xie J,Wang J,Li R,Dai Q,Yong Y,Zong B,Xu Y,Li E,Ferro A,Xu B

    更新日期:2012-08-01 00:00:00

  • Cardiac-specific deficiency of the mitochondrial calcium uniporter augments fatty acid oxidation and functional reserve.

    abstract::The mitochondrial calcium uniporter (MCU) relays cytosolic Ca2+ transients to the mitochondria. We examined whether energy metabolism was compromised in hearts from mice with a cardiac-specific deficiency of MCU subjected to an isoproterenol (ISO) challenge. Surprisingly, isolated working hearts from cardiac MCU-defic...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Altamimi TR,Karwi QG,Uddin GM,Fukushima A,Kwong JQ,Molkentin JD,Lopaschuk GD

    更新日期:2019-02-01 00:00:00

  • Enhanced Ca2+ channel currents in cardiac hypertrophy induced by activation of calcineurin-dependent pathway.

    abstract::Cardiac-specific expression of an activated calcineurin protein in the hearts of transgenic (CLN) mice produces a profound hypertrophy that rapidly progresses to heart failure. While calcineurin is regulated by Ca2+, the potential effects of calcineurin on cardiac myocyte Ca2+ handling has not been evaluated. To this ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Yatani A,Honda R,Tymitz KM,Lalli MJ,Molkentin JD

    更新日期:2001-02-01 00:00:00

  • The effect of ouabain on hearts of cardiomyopathic hamsters: potentiation by isoproterenol.

    abstract::The isometric twitch properties of papillary muscles from hearts of 30- to 53-day-old cardiomyopathic hamsters (BIO 14.6) were studied before and after exposure to the cardiac glycoside, ouabain. The diseased tissue was weakly responsive to ouabain (3 to 100 microM), as compared to a more appreciable positive inotropi...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Rossner KL,Mascarenhas DA

    更新日期:1987-06-01 00:00:00

  • Organization and function of sarcolemmal phospholipids in control and ischemic/reperfused cardiomyocytes.

    abstract::The topic of this review is the lipidic part of the sarcolemma, the plasma membrane of the myocardial cell, and its role in (dis)function of the cardiomyocyte. First the isolation of the sarcolemma and its lipid composition are discussed. These phospholipids are not randomly distributed over the two monolayers of the ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审


    authors: Post JA,Verkleij AJ,Langer GA

    更新日期:1995-02-01 00:00:00

  • Flecainide inhibits arrhythmogenic Ca2+ waves by open state block of ryanodine receptor Ca2+ release channels and reduction of Ca2+ spark mass.

    abstract::Catecholaminergic polymorphic ventricular tachycardia (CPVT) is linked to mutations in the cardiac ryanodine receptor (RyR2) or calsequestrin. We recently found that the drug flecainide inhibits RyR2 channels and prevents CPVT in mice and humans. Here we compared the effects of flecainide and tetracaine, a known RyR2 ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Hilliard FA,Steele DS,Laver D,Yang Z,Le Marchand SJ,Chopra N,Piston DW,Huke S,Knollmann BC

    更新日期:2010-02-01 00:00:00

  • Translational potential of thyroid hormone and its analogs.

    abstract::Thyroid hormone has unique properties affecting the heart, and the vasculature and cholesterol metabolism. There is interest in using thyromimetic agents as possible treatment options for heart failure based on data demonstrating the ability of these agents to improve systolic and diastolic left ventricular function a...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审


    authors: Arsanjani R,McCarren M,Bahl JJ,Goldman S

    更新日期:2011-10-01 00:00:00

  • Ischemia-induced noradrenaline release in the isolated rat heart: influence of perfusion substrate and duration of ischemia.

    abstract::To examine some of the characteristics of the local noradrenaline (NA) release in myocardial ischemia a study was made on Langendorff-perfused rat hearts, prelabelled with 3H-NA. The left coronary artery was ligated for 15, 30, 60 or 120 min, followed by 10 min of reperfusion. The coronary effluent was collected and a...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Abrahamsson T,Almgren O,Carlsson L

    更新日期:1983-12-01 00:00:00

  • Mitochondrial adaptations within chronically ischemic swine myocardium.

    abstract::Experimental evidence has emerged that myocardial ischemic preconditioning can prime the mitochondria into a "stress-resistant state", so that cell death is reduced following prolonged severe ischemia and reperfusion. Using a swine model of chronically ischemic myocardium, we tested the hypothesis that mitochondria wi...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: McFalls EO,Sluiter W,Schoonderwoerd K,Manintveld OC,Lamers JM,Bezstarosti K,van Beusekom HM,Sikora J,Ward HB,Merkus D,Duncker DJ

    更新日期:2006-12-01 00:00:00

  • The effect of alterations to action potential duration on beta-adrenoceptor-mediated aftercontractions in human and guinea-pig ventricular myocytes.

    abstract::Aftercontractions induced by beta-adrenoceptor stimulation in human and guinea-pig cardiomyocytes may be related to changes in action potential duration (APD). We investigated the effects of altering APD during the occurrence of isoproterenol-induced aftercontractions, using the KATP channel openers cromakalim and lem...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Tweedie D,O'Gara P,Harding SE,MacLeod KT

    更新日期:1997-05-01 00:00:00

  • Alterations in the baroreceptor reflex control of heart rate in streptozotocin diabetic rats.

    abstract::Baroreflex control of heart rate was studied in conscious diabetic rats at 12, 24 and 48 weeks after the induction of diabetes with streptozotocin. Baseline blood pressure (mean arterial blood pressure) of diabetic rats was significantly lower at 12 weeks after the induction of diabetes when compared to age-matched co...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Chang KS,Lund DD

    更新日期:1986-06-01 00:00:00

  • Lysozyme binding to endocardial endothelium mediates myocardial depression by the nitric oxide guanosine 3',5' monophosphate pathway in sepsis.

    abstract::Inflammatory mediators have been implicated as a cause of reversible myocardial depression in septic shock. We previously reported that the release of lysozyme-c (Lmz-S) from leukocytes from the spleen or other organs contributes to myocardial dysfunction in Escherichia coli septic shock in dogs by binding to a cardia...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Mink SN,Bose R,Roberts DE,Jacobs H,Duke K,Bose D,Cheng ZQ,Light RB

    更新日期:2005-10-01 00:00:00

  • Early LQT2 nonsense mutation generates N-terminally truncated hERG channels with altered gating properties by the reinitiation of translation.

    abstract::Mutations in the human ether-a-go-go-related gene (hERG) result in long QT syndrome type 2 (LQT2). The hERG gene encodes a K(+) channel that contributes to the repolarization of the cardiac action potential. We have previously shown that hERG mRNA transcripts that contain premature termination codon mutations are rapi...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Stump MR,Gong Q,Packer JD,Zhou Z

    更新日期:2012-11-01 00:00:00

  • Loading of calcium and strontium into the sarcoplasmic reticulum in rat ventricular muscle.

    abstract::Previous work suggests that strontium ions (Sr(2+)) are less effective than calcium ions (Ca(2+)) at supporting excitation-contraction (EC) coupling in cardiac muscle. We therefore tested whether this was due to differences in the uptake and release of Ca(2+)and Sr(2+)by the sarcoplasmic reticulum (SR) of rat ventricu...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Spencer CI,Barsotti RJ,Berlin JR

    更新日期:2000-07-01 00:00:00

  • Captopril treatment improves the sarcoplasmic reticular Ca(2+) transport in heart failure due to myocardial infarction.

    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


    authors: Shao Q,Ren B,Zarain-Herzberg A,Ganguly PK,Dhalla NS

    更新日期:1999-09-01 00:00:00

  • An in vitro model for the assessment of stem cell fate following implantation within the infarct microenvironment identifies ISL-1 expression as the strongest predictor of c-Kit(+) cardiac progenitor cells' therapeutic potential.

    abstract::Cell therapy has the potential to drastically improve clinical outcomes for the 1.45 million patients suffering from a myocardial infarction (MI) each year in the U.S. However, the limitations associated with this treatment - including poor engraftment, significant cell death and poor differentiation potential - have ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Sullivan KE,Burns LJ,Black LD 3rd

    更新日期:2015-11-01 00:00:00

  • Further investigations into the mechanism of antifibrillatory action of the specific IK1 blocker, RP58866, assessed using the rat dual coronary perfusion model.

    abstract::RP58866 (1-[-2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]-4- (3,4-dimethoxyphenyl)-piperidine), a specific blocker of the inwardly rectifying K+ current (IK1), is an extremely effective antiarrhythmic agent in rat, rabbit and primate (marmoset) isolated hearts in the settings of acute ischaemia and reperfusion (Rees and...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Rees SA,Curtis MJ

    更新日期:1995-12-01 00:00:00

  • Therapeutic targeting of autophagy in cardiovascular disease.

    abstract::Autophagy is an evolutionarily ancient process of intracellular catabolism necessary to preserve cellular homeostasis in response to a wide variety of stresses. In the case of post-mitotic cells, where cell replacement is not an option, finely tuned quality control of cytoplasmic constituents and organelles is especia...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审


    authors: Schiattarella GG,Hill JA

    更新日期:2016-06-01 00:00:00

  • Atorvastatin-induced increase in progenitor cell levels is rather caused by enhanced receptor activator of NF-kappaB ligand (RANKL) cell proliferation than by bone marrow mobilization.

    abstract:BACKGROUND:Statins have been shown to increase the level of circulating progenitor cells in peripheral blood supposedly due to a mobilization of progenitor cells from the bone marrow niche. Osteoclast/osteoblast interaction has been associated with progenitor cell mobilization. Here, we investigated the role of statins...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Steinmetz M,Pelster B,Lucanus E,Arnal JF,Nickenig G,Werner N

    更新日期:2013-04-01 00:00:00

  • A functional role of the C-terminal 42 amino acids of SUR2A and SUR2B in the physiology and pharmacology of cardiovascular ATP-sensitive K(+) channels.

    abstract::The ATP-sensitive K(+) (K(ATP)) channel is composed of four pore-forming Kir6.2 subunits and four sulfonylurea receptors (SUR). Intracellular ATP inhibits K(ATP) channels through Kir6.2. SUR is an ABC protein bearing transmembrane domains and two nucleotide-binding domains (NBD1 and NBD2). SUR increases the open proba...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Yamada M,Kurachi Y

    更新日期:2005-07-01 00:00:00