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










  • Time course of the apoptotic cascade and effects of caspase inhibitors in adult rat ventricular cardiomyocytes.

    abstract::K. Suzuki, S. Kostin, V. Person, A. Elsässer and J. Schaper. Time Course of the Apoptotic Cascade and Effects of Caspase Inhibitors in Adult Rat Ventricular Cardiomyocytes. Journal of Molecular and Cellular Cardiology (2001) 33, 983-994. Interpretation of the rate of apoptosis in diseased hearts is hampered by the fac...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Suzuki K,Kostin S,Person V,Elsässer A,Schaper J

    更新日期:2001-05-01 00:00:00

  • Myosin phosphorylation decreases the ATPase activity of cardiac myofibrils.

    abstract::Our previous work showed that myosin phosphorylation decreased the ATPase activity of skeletal muscle myofibrils that were lightly fixed with glutaraldehyde. The fixation process prevented sarcomere shortening and destruction of the ordered filament array upon the addition of ATP. We have now extended these results to...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Franks K,Cooke R,Stull JT

    更新日期:1984-07-01 00:00:00

  • May the fibrosis be with you: Is discoidin domain receptor 2 the receptor we have been looking for?

    abstract::In a recent issue of Journal of Molecular and Cellular Cardiology, George et al. [1] identified discoidin domain receptor 2 (DDR2) as a positive modulator of collagen production in cardiac fibroblasts stimulated with angiotensin II (Ang II). DDR2 is a tyrosine kinase collagen receptor and is associated with pathologic...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 社论


    authors: DeLeon-Pennell KY

    更新日期:2016-02-01 00:00:00

  • The response to ischemia in blood perfused vs. crystalloid perfused isolated rat heart preparations.

    abstract::With a research hypothesis that the behavior of blood perfused hearts was different from that of crystalloid perfused hearts, we tested the null hypothesis that the functional and metabolic status of blood-perfused (paracorporeal oxygenation) and Krebs-Henseleit (bubble oxygenation) perfused Langendorff isolated rat h...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Walters HL 3rd,Digerness SB,Naftel DC,Waggoner JR 3rd,Blackstone EH,Kirklin JW

    更新日期:1992-10-01 00:00:00

  • Evidence for a sustained effectiveness of sodium-channel activators in failing human myocardium.

    abstract::Elevation of cytosolic sodium is thought to be correlated with an increase in force of contraction due to an activation of sodium-calcium exchange. We investigated the inotropic response mediated by the new sodium-channel activator BDF 9148 (0.01-100 mumol/l) on failing human myocardium. Force of contraction was studi...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Schwinger RH,Böhm M,Mittmann C,La Rosée K,Erdmann E

    更新日期:1991-04-01 00:00:00

  • Protection of energy status of hypoxic cardiomyocytes by mild acidosis.

    abstract::The question was investigated whether mild acidosis can provide energetic protection on the hypoxic myocardial cell by mechanisms other than negative inotropy. The experimental model used was quiescent ventricular cardiomyocytes isolated from the adult rat. The extracellular pH (pHe) in modified hypoxic Tyrode's solut...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Koop A,Piper HM

    更新日期:1992-01-01 00:00:00

  • Contractile responses of isolated adult rat and rabbit cardiac myocytes to isoproterenol and calcium.

    abstract::Myocytes were isolated by Langendorff perfusion of rat or rabbit hearts with low calcium solution followed by collagenase and hyaluronidase, or by incubation of chunks of rat ventricular tissue in similar media. Cells were then placed in a bath on a microscope stage, superfused and electrically stimulated. Contraction...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Harding SE,Vescovo G,Kirby M,Jones SM,Gurden J,Poole-Wilson PA

    更新日期:1988-07-01 00:00:00

  • Myocardial dysfunction and ultrastructural alterations mediated by oxygen metabolites.

    abstract::The direct effect of oxygen metabolites was studied on isolated perfused rat hearts. Superoxide anion (O2-.) and hydrogen peroxide (H2O2) were generated by adding purine (2.3 mM) and purified xanthine oxidase (0.06 U/ml) to Krebs-Henseleit buffer (pH 7.4). Xanthine oxidase was added to the purine-containing perfusate ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Miki S,Ashraf M,Salka S,Sperelakis N

    更新日期:1988-11-01 00:00:00

  • Viral expression of a SERCA2a-activating PLB mutant improves calcium cycling and synchronicity in dilated cardiomyopathic hiPSC-CMs.

    abstract::There is increasing momentum toward the development of gene therapy for heart failure (HF) that is defined by impaired calcium (Ca2+) transport and reduced contractility. We have used FRET (fluorescence resonance energy transfer) between fluorescently-tagged SERCA2a (the cardiac Ca2+ pump) and PLB (phospholamban, vent...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Stroik DR,Ceholski DK,Bidwell PA,Mleczko J,Thanel PF,Kamdar F,Autry JM,Cornea RL,Thomas DD

    更新日期:2020-01-01 00:00:00

  • Skeletal muscle metabolism in experimental heart failure.

    abstract::We studied peripheral skeletal muscle metabolism in monocrotaline-treated rats. Two distinct groups emerged: a percentage of the animals developed ventricular hypertrophy, with no signs of heart failure (compensated group), whilst others, besides ventricular hypertrophy, developed the syndrome of congestive heart fail...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Bernocchi P,Ceconi C,Pedersini P,Pasini E,Curello S,Ferrari R

    更新日期:1996-11-01 00:00:00

  • Muscarinic stimulation and pinacidil produce similar facilitation of tachyarrhythmia induction in rat isolated atria.

    abstract::Atrial tachyarrhythmias, the most common type of cardiac arrhythmias, are associated with greater stroke risk. Muscarinic cholinergic agonists have been shown to facilitate atrial tachyarrhythmia maintenance in the absence of cardiac disease. This has been attributed to action potential shortening, which enhances myoc...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Zafalon N Jr,Oshiyama NF,Bassani JW,Bassani RA

    更新日期:2013-12-01 00:00:00

  • Comparative study on isolation and mitochondrial function of adult mouse and rat cardiomyocytes.

    abstract:BACKGROUND:Cultured adult mouse and rat cardiomyocytes are the best and low-cost cell model for cardiac cellular physiology, pathology, drug toxicity screening, and intervention. The functions of mouse cardiomyocytes decline faster than rat cardiomyocytes in culture conditions. However, little is known about the differ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Liu B,Li A,Qin Y,Tian X,Gao M,Jiang W,Gong G

    更新日期:2019-11-01 00:00:00

  • Structural vs. contractile protein remodeling and myocardial stiffness in hypertrophied rat left ventricle.

    abstract::Left ventricular pressure overload will result in the hypertrophic growth of the myocardium and in the rat may include a remodeling of both the structural and contractile proteins. As a result, an adaptive rise in active stiffness, or the force generating capacity of the myocardium, may occur. The relative importance ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Jalil JE,Doering CW,Janicki JS,Pick R,Clark WA,Abrahams C,Weber KT

    更新日期:1988-12-01 00:00:00

  • The effect of PKA-mediated phosphorylation of ryanodine receptor on SR Ca2+ leak in ventricular myocytes.

    abstract::Functional impact of cardiac ryanodine receptor (type 2 RyR or RyR2) phosphorylation by protein kinase A (PKA) remains highly controversial. In this study, we characterized a functional link between PKA-mediated RyR2 phosphorylation level and sarcoplasmic reticulum (SR) Ca2+ release and leak in permeabilized rabbit ve...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Bovo E,Huke S,Blatter LA,Zima AV

    更新日期:2017-03-01 00:00:00

  • Short-term caloric restriction improves ischemic tolerance independent of opening of ATP-sensitive K+ channels in both young and aged hearts.

    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


    authors: Shinmura K,Tamaki K,Bolli R

    更新日期:2005-08-01 00:00:00

  • Heat-shock protein 90 modulates cardiac ventricular hypertrophy via activation of MAPK pathway.

    abstract::The Raf/MAPK/ERK kinase (Mek)/extracellular signal-regulated kinases (Erk) pathway is activated in cardiac hypertrophy after a myocardial infarction. Although heat-shock protein 90 (Hsp90) may regulate the Raf/Mek/Erk signal pathway, the role of Hsp90 in pathophysiological cardiac hypertrophy remains unclear. In this ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Tamura S,Marunouchi T,Tanonaka K

    更新日期:2019-02-01 00:00:00

  • Human cardiac phospholipase D activity is tightly controlled by phosphatidylinositol 4,5-bisphosphate.

    abstract::Phospholipase D (PLD) plays a central role in receptor-mediated breakdown of choline phospholipids and formation of phosphatidic acid (PA), an important regulator of cardiac function. However, specific mechanisms that regulate myocardial PLD activity remain largely unknown, particularly in the human heart. We hypothes...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Kurz T,Kemken D,Mier K,Weber I,Richardt G

    更新日期:2004-02-01 00:00:00

  • Effect of alpha-tocopherol on high energy phosphate metabolite levels in rat heart by 31P-NMR using a Langendorff perfusion technique.

    abstract::To examine the action of alpha-tocopherol on high energy phosphate compounds, a 31P-NMR technique was applied to perfused Langendorff rat hearts. Rats were treated with tocopherol acetate (25 mg/kg body wt i.p.) for 7 consecutive days. On the 7th day, the rat hearts were isolated for the Langendorff experiment. After ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Kotegawa M,Sugiyama M,Shoji T,Haramaki N,Ogura R

    更新日期:1993-09-01 00:00:00

  • Evidences of antagonism between amiodarone and triiodothyronine on the K+ channel activities of cultured rat cardiomyocytes.

    abstract::Effects of acute and chronic treatments with amiodarone, both in the presence and the absence of exogenous triiodothyronine (T3), on repolarizing outward K+ currents were investigated by patch-clamp technique in cultured newborn rat ventricular cells. Acute exposure to amiodarone dose-dependently inhibited the transie...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Guo W,Kamiya K,Toyama J

    更新日期:1997-02-01 00:00:00

  • MicroRNA-25-dependent up-regulation of NADPH oxidase 4 (NOX4) mediates hypercholesterolemia-induced oxidative/nitrative stress and subsequent dysfunction in the heart.

    abstract::Diet-induced hypercholesterolemia leads to oxidative/nitrative stress and subsequent myocardial dysfunction. However, the regulatory role of microRNAs in this phenomenon is unknown. We aimed to investigate, whether hypercholesterolemia-induced myocardial microRNA alterations play a role in the development of oxidative...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Varga ZV,Kupai K,Szűcs G,Gáspár R,Pálóczi J,Faragó N,Zvara A,Puskás LG,Rázga Z,Tiszlavicz L,Bencsik P,Görbe A,Csonka C,Ferdinandy P,Csont T

    更新日期:2013-09-01 00:00:00

  • Lidocaine blocks Na, Ca and K currents of chick ventricular myocytes.

    abstract::In addition to the well-known reduction in the maximal rate of rise the antiarrhythmic agent, lidocaine, also produces a shortening in the duration of the normal ventricular action potential. The voltage-dependent currents carried by Na, Ca and K ions were examined in the absence and presence of lidocaine, in order to...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Josephson IR

    更新日期:1988-07-01 00:00:00

  • Reduced myocardial Na+, K(+)-pump capacity in congestive heart failure following myocardial infarction in rats.

    abstract::We examined changes in expression and function of the cardiac Na+, K(+)-pump in a post-infarction rat model of hypertrophy and congestive heart failure (CHF). Myocardial infarction was induced by ligation of the left coronary artery in Wistar rats and hearts were obtained from animals with CHF and from sham operated r...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Semb SO,Lunde PK,Holt E,Tønnessen T,Christensen G,Sejersted OM

    更新日期:1998-07-01 00:00:00

  • Increased sympathoadrenomedullary activity and left ventricular hypertrophy in young patients with borderline hypertension.

    abstract::Echocardiographic dimensions and endocrinological examination were performed in 71 young patients with borderline hypertension (BHT) and 31 age-matched normotensive subjects (NT). Patients with BHT had significantly higher relative wall thickness (RWT) and left ventricular mass index than NT, although all BHT patients...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Fujita T,Noda H,Ito Y,Isaka M,Sato Y,Ogata E

    更新日期:1989-12-01 00:00:00

  • Dose-dependent increase in sensitivity to calcium-induced mitochondrial dysfunction and cardiomyocyte cell injury by doxorubicin.

    abstract::We previously reported the induction of calcium-dependent calcium release and depolarization of membrane potential of cardiac mitochondria from rats treated chronically (13 weeks) with doxorubicin. The fact that this was inhibited by cyclosporine A and ruthenium red suggests induction of the mitochondrial permeability...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Solem LE,Heller LJ,Wallace KB

    更新日期:1996-05-01 00:00:00

  • Myosin binding protein C phosphorylation in normal, hypertrophic and failing human heart muscle.

    abstract::Phosphorylation of myosin binding protein C (MyBP-C) was investigated in intraventricular septum samples taken from patients with hypertrophic cardiomyopathy undergoing surgical septal myectomy. These samples were compared with donor heart muscle, as a well-characterised control tissue, and with end-stage failing hear...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Jacques AM,Copeland O,Messer AE,Gallon CE,King K,McKenna WJ,Tsang VT,Marston SB

    更新日期:2008-08-01 00:00:00

  • Selective inhibition of plasma membrane calcium ATPase 4 improves angiogenesis and vascular reperfusion.

    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


    authors: Kurusamy S,López-Maderuelo D,Little R,Cadagan D,Savage AM,Ihugba JC,Baggott RR,Rowther FB,Martínez-Martínez S,Arco PG,Murcott C,Wang W,Francisco Nistal J,Oceandy D,Neyses L,Wilkinson RN,Cartwright EJ,Redondo JM,Armesi

    更新日期:2017-08-01 00:00:00

  • Effect of thyroid hormone on protein turnover in cultured cardiac myocytes.

    abstract::Since systemic actions of thyroid hormone increase cardiac work, direct effects of T3 on myocardial protein turnover may be obscured in the intact animal. For this reason, the effects of T3 on synthesis and degradation of cellular protein were measured in replicate cultures of cardiac myocytes obtained from chick embr...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Carter WJ,van der Weijden Benjamin WS,Faas FH

    更新日期:1985-09-01 00:00:00

  • Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease.

    abstract::The key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Ounzain S,Pezzuto I,Micheletti R,Burdet F,Sheta R,Nemir M,Gonzales C,Sarre A,Alexanian M,Blow MJ,May D,Johnson R,Dauvillier J,Pennacchio LA,Pedrazzini T

    更新日期:2014-11-01 00:00:00

  • Phospholipid reorganization and bilayer destabilization during myocardial ischemia and reperfusion: a hypothesis.

    abstract::The ultrastructure of myocardial tissue was studied during ischemia and reperfusion and during reperfusion with a calcium-containing solution after a short period of calcium-free perfusion (calcium paradox). After ischemia an aggregation of the sarcolemmal intramembranous particles was observed. Subsequent reperfusion...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Post JA,Ruigrok TJ,Verkleij AJ

    更新日期:1988-03-01 00:00:00

  • Expression of aquaporin 1 in human cardiac and skeletal muscle.

    abstract::Aquaporins (AQPs) are a family of water channel proteins that assist in maintenance of the cellular osmotic environment and whole body fluid balance. Specialized organ-specific AQPs are important in physiologic and pathologic processes but little is known about AQPs in the human heart. AQP1 has been identified in rode...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Au CG,Cooper ST,Lo HP,Compton AG,Yang N,Wintour EM,North KN,Winlaw DS

    更新日期:2004-05-01 00:00:00