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

Abstract:

: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.

journal_name

J Mol Cell Cardiol

authors

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

doi

10.1016/j.yjmcc.2015.10.030

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

232-40

issue

Pt B

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(15)30098-5

journal_volume

89

pub_type

杂志文章
  • Protein kinase C-epsilon is responsible for the protection of preconditioning in rabbit cardiomyocytes.

    abstract::The role of protein kinase C (PKC) in the protection of ischemic preconditioning (PC) is still controversial, partly because of the multiple isozymes of PKC and the inability to directly measure PKC activity in vivo. In this study we have used novel peptide inhibitors which correspond to part of the amino acid sequenc...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1999.1026

    authors: Liu GS,Cohen MV,Mochly-Rosen D,Downey JM

    更新日期:1999-10-01 00:00:00

  • Differential regulation of the cardiac sodium calcium exchanger promoter in adult and neonatal cardiomyocytes by Nkx2.5 and serum response factor.

    abstract::Nkx2.5 and serum response factor (SRF) are critically important transcription factors in cardiac morphogenesis. They are also widely expressed in adult cardiomyocytes, but there is little data to indicate their possible role in adult cardiac cells. In this paper we demonstrate that the interaction of Nkx2.5 and SRF in...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2002.2019

    authors: Müller JG,Thompson JT,Edmonson AM,Rackley MS,Kasahara H,Izumo S,McQuinn TC,Menick DR,O'Brien TX

    更新日期:2002-07-01 00:00:00

  • Akt2 deficiency promotes cardiac induction of Rab4a and myocardial β-adrenergic hypersensitivity.

    abstract::Patients with diabetes mellitus can develop cardiac dysfunction in the absence of underlying coronary artery disease or hypertension; a condition defined as diabetic cardiomyopathy. Mice lacking the intracellular protein kinase Akt2 develop a syndrome that is similar to diabetes mellitus type 2. Expression profiling o...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2010.08.011

    authors: Etzion S,Etzion Y,DeBosch B,Crawford PA,Muslin AJ

    更新日期:2010-12-01 00:00:00

  • A crosstalk between chromatin remodeling and histone H3K4 methyltransferase complexes in endothelial cells regulates angiotensin II-induced cardiac hypertrophy.

    abstract::Angiotensin II (Ang II) induces cardiac hypertrophy and fibrosis in part by stimulating endothelin (ET-1) transcription. The involvement of the epigenetic machinery in this process is largely undefined. In the present study, we examined the epigenetic maneuvering underlying cardiac hypertrophy and fibrosis following E...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2015.02.010

    authors: Weng X,Yu L,Liang P,Li L,Dai X,Zhou B,Wu X,Xu H,Fang M,Chen Q,Xu Y

    更新日期:2015-05-01 00:00:00

  • Specific effects of n-3 fatty acids and 8-bromo-cGMP on the cyclic nucleotide phosphodiesterase activity in neonatal rat cardiac myocytes.

    abstract::The authors have previously resolved four forms of cyclic nucleotide phosphodiesterase (PDE) in neonatal rat cultured cardiomyocytes by use of high-performance liquid chromatography (HPLC) and have shown that the response of the cGMP-stimulated PDE to the effector cGMP was markedly reduced as compared to that of the c...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1996.0207

    authors: Picq M,Dubois M,Grynberg A,Lagarde M,Prigent AF

    更新日期:1996-10-01 00:00:00

  • Relative abundance of alpha2 Na(+) pump isoform influences Na(+)-Ca(2+) exchanger currents and Ca(2+) transients in mouse ventricular myocytes.

    abstract::In the mouse, genetic reduction in the Na(+), K(+)-ATPase alpha1 or alpha2 isoforms results in different functional phenotypes: heterozygous alpha2 isolated hearts are hypercontractile, whereas heterozygous alpha1 hearts are hypocontractile. We examined Na(+)/Ca(2+) exchange (NCX) currents in voltage clamped myocytes ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2005.03.023

    authors: Yamamoto T,Su Z,Moseley AE,Kadono T,Zhang J,Cougnon M,Li F,Lingrel JB,Barry WH

    更新日期:2005-07-01 00:00:00

  • Renal studies provide an insight into cardiac extracellular matrix remodeling during health and disease.

    abstract::The remodeling of a heart ventricle after myocardial infarction involves numerous inflammatory mediators that may trigger a long-lasting and a highly fibrogenic process. Likewise, in the kidney, acute and chronic injuries may lead to abnormal extracellular matrix deposition and eventually lead to the loss of renal fun...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2009.07.022

    authors: Hertig A,Gangadhar T,Kalluri R

    更新日期:2010-03-01 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

    doi:10.1016/j.yjmcc.2019.09.006

    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

  • Effects of ACE-inhibition on redox status and expression of P-selectin of endothelial cells subjected to oxidative stress.

    abstract::Redox stress during post-ischemic reperfusion may be the prime signal for processes leading to myocardial remodelling and hypertrophy. Nitric oxide (NO) is antioxidative, antiadhesive for neutrophils (PMN) and antiproliferative. Thus, enhancing endothelial production of NO, e.g. by inhibiting breakdown of endogenous b...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1997.0530

    authors: Zahler S,Kupatt C,Möbert J,Becker BF,Gerlach E

    更新日期:1997-11-01 00:00:00

  • Differential stress protein mRNA expression during early ischaemic preconditioning in the rabbit heart and its relationship to adenosine receptor function.

    abstract::The aim of this study was: (1) to elucidate in more detail the relationship between stress protein expression and brief periods of ischaemia and reperfusion, such as occur during early (classical) ischaemic preconditioning (PC) in the rabbit myocardium; (2) to determine whether stress protein expression is affected by...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(95)91299-1

    authors: Heads RJ,Latchman DS,Yellon DM

    更新日期:1995-10-01 00:00:00

  • Effect of treatment on ventricular function and troponin I proteolysis in reperfused myocardium.

    abstract::Effects of ischemia time and treatment interventions upon troponin I (TnI) proteolysis and function of reperfused myocardium were examined in isolated, perfused rabbit hearts. Hearts were randomized to 90 min aerobic perfusion, 15 min low-flow (1 ml/min) ischemia (I) and 60 min reperfusion (R) or 60 min low-flow I and...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2002.1522

    authors: Prasan AM,McCarron HC,Hambly BD,Fermanis GG,Sullivan DR,Jeremy RW

    更新日期:2002-04-01 00:00:00

  • Appearance and regression of rat pouch tissue.

    abstract::Fibrosis, a consequence of tissue repair, can become a final common pathway to organ failure, if progressive. Prevention and regression of organ fibrosis represent targets of considerable interest. The natural fate of fibrosis differs among various tissues being either persistent, progressive or regressive. Cellular a...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1999.0944

    authors: Zhang J,Sun Y,Zhang JQ,Ramires FJ,Weber KT

    更新日期:1999-05-01 00:00:00

  • Quantifying antiarrhythmic drug blocking during action potentials in guinea-pig papillary muscle.

    abstract::This report examines the blocking effects that several antiarrhythmic drugs have on rapid upstroke velocities of action potentials recorded from guinea-pig papillary muscle. A mathematical analysis is developed, that measures an effective "blocking rate' that acts during the action potential with the purpose being to ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(83)90334-6

    authors: Courtney KR

    更新日期:1983-11-01 00:00:00

  • [32P]phosphate autoradiography as an indicator of regional myocardial oxygen consumption?

    abstract::The present study was undertaken to assess whether [32P]uptake and autoradiography could be used as an indicator of regional myocardial oxygen consumption. Rat hearts were perfused in the Langendorff mode with medium containing [32P]orthophosphate (32Pi) and the incorporation of label into ATP, perchloric acid-insolub...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1993.1035

    authors: Richards SM,Rattigan S,Colquhoun EQ,Clark MG

    更新日期:1993-03-01 00:00:00

  • Remote ischemic postconditioning enhances cell retention in the myocardium after intravenous administration of bone marrow mesenchymal stromal cells.

    abstract::Efficacy of intravenous administration of mesenchymal stromal cells (MSCs) for myocardial infarction (MI) is limited by low cell retention in the damaged myocardium. Previous studies indicated that remote ischemic conditioning could protect against ischemia-reperfusion-induced injury by release of various cytokines in...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2012.12.016

    authors: Jiang Q,Song P,Wang E,Li J,Hu S,Zhang H

    更新日期:2013-03-01 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

    doi:10.1006/jmcc.2000.1162

    authors: Spencer CI,Barsotti RJ,Berlin JR

    更新日期:2000-07-01 00:00:00

  • Human eHAND, but not dHAND, is down-regulated in cardiomyopathies.

    abstract::The progression of cardiomyopathy to congestive heart failure is often associated with the expression of fetal cardiac-specific genes. In mice, the basic helix-loop-helix transcription factors, dHAND and eHAND, are expressed in a cardiac chamber-specific fashion and are essential for fetal cardiac development, but are...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2001.1434

    authors: Natarajan A,Yamagishi H,Ahmad F,Li D,Roberts R,Matsuoka R,Hill S,Srivastava D

    更新日期:2001-09-01 00:00:00

  • Mechanical strain induces a pro-fibrotic phenotype in human mitral valvular interstitial cells through RhoC/ROCK/MRTF-A and Erk1/2 signaling pathways.

    abstract::The mitral valve is a complex multilayered structure populated by fibroblast-like cells, valvular interstitial cells (VIC) which are embedded in an extracellular matrix (ECM) scaffold and are submitted to the mechanical deformations affecting valve at each heartbeat, for an average of 40 million times per year. Myxoma...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2019.08.008

    authors: Blomme B,Deroanne C,Hulin A,Lambert C,Defraigne JO,Nusgens B,Radermecker M,Colige A

    更新日期:2019-10-01 00:00:00

  • Acute AT1R blockade prevents isoproterenol-induced injury in mdx hearts.

    abstract:BACKGROUND:Duchenne muscular dystrophy (DMD) is an X-linked disease characterized by skeletal muscle degeneration and a significant cardiomyopathy secondary to cardiomyocyte damage and myocardial loss. The molecular basis of DMD lies in the absence of the protein dystrophin, which plays critical roles in mechanical mem...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2019.01.013

    authors: Meyers TA,Heitzman JA,Krebsbach AM,Aufdembrink LM,Hughes R,Bartolomucci A,Townsend D

    更新日期:2019-03-01 00:00:00

  • The effect of vitamin D3 deficiency on the isolated chick heart: hemodynamic, P-31 NMR and membrane studies.

    abstract::The purpose of this study was to investigate whether vitamin D3 deficiency affects the cardiac function of chick hearts directly or whether the influence is secondary through the hormone's effect on serum calcium levels. To this end, three experimental groups were studied: (a) the control group of vitamin D3 supplemen...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1993.1010

    authors: Hochhauser E,Kushnir T,Navon G,Rehavi M,Barak J,Edelstein S,Vidne B

    更新日期:1993-01-01 00:00:00

  • Mitochondrial reactive oxygen species production and elimination.

    abstract::Reactive oxygen species (ROS) play an important role in cardiovascular diseases, and one important source for ROS are mitochondria. Emission of ROS from mitochondria is the net result of ROS production at the electron transport chain (ETC) and their elimination by antioxidative enzymes. Both of these processes are hig...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2014.03.011

    authors: Nickel A,Kohlhaas M,Maack C

    更新日期:2014-08-01 00:00:00

  • A study of the effects of substrates on intracellular pH in toad ventricular strips.

    abstract::The ability of different substrates to affect myocardial function is well established but the mechanism for this effect has yet to be determined. To explore this area further, the studies described below were designed to determine the effect of different metabolic substrates, glucose or pyruvate, on myocardial respons...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(86)80943-9

    authors: Snow TR

    更新日期:1986-07-01 00:00:00

  • Heart mitochondria contain functional ATP-dependent K+ channels.

    abstract::Recent observations challenged the functional importance or even the existence of mitochondrial ATP-dependent K+ (mitoK(ATP)) channels. In the present study, we determined the presence of K(ATP)-channel subunits in mouse heart mitochondria, and investigated whether known openers or blockers of the channel can alter mi...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(03)00249-9

    authors: Lacza Z,Snipes JA,Miller AW,Szabó C,Grover G,Busija DW

    更新日期:2003-11-01 00:00:00

  • Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload.

    abstract:AIMS:Biglycan, a small leucine-rich proteoglycan, has been shown to play an important role in stabilizing fibrotic scars after experimental myocardial infarction. However, the role of biglycan in the development and regression of cardiomyocyte hypertrophy and fibrosis during cardiac pressure overload and unloading rema...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2016.10.011

    authors: Beetz N,Rommel C,Schnick T,Neumann E,Lother A,Monroy-Ordonez EB,Zeeb M,Preissl S,Gilsbach R,Melchior-Becker A,Rylski B,Stoll M,Schaefer L,Beyersdorf F,Stiller B,Hein L

    更新日期:2016-12-01 00:00:00

  • Effects of ischemia and perfusion temperature on the synthesis of stress-induced (heat shock) proteins in isolated and perfused rat hearts.

    abstract::Isolated and perfused rat hearts were examined by 2-dimensional gel electrophoresis and liquid scintillation counting to determine the effect of ischemia or perfusion temperature on protein synthesis. Isolated hearts were subjected to ischemia at either 4 degrees, 20 degrees, or 30 degrees C and then perfused at 37 de...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(87)80390-5

    authors: Currie RW

    更新日期:1987-08-01 00:00:00

  • Release of endothelin from cultured bovine endothelial cells.

    abstract::Recently discovered endothelin is a powerful vasoconstrictor of vascular smooth muscle in vitro, which also profoundly affects the mechanical function of the heart. An increased level of plasma endothelin in patients with acute myocardial infarction suggests the enhanced release of endothelin from vascular endothelium...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(91)90974-q

    authors: Prasad MR,Jones RM,Kreutzer DL

    更新日期:1991-06-01 00:00:00

  • Transcriptomic analysis reveals atrial KCNE1 down-regulation following lung lobectomy.

    abstract::Lone atrial fibrillation (AF) is associated with various ion channel gene sequence variants, notably the common S38G loss-of-function polymorphism in the KCNE1 K(+) channel ancillary subunit gene. New-onset postoperative AF (POAF) generally occurs 48-72 h after major surgery, particularly following procedures within t...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2012.05.010

    authors: Heerdt PM,Kant R,Hu Z,Kanda VA,Christini DJ,Malhotra JK,Abbott GW

    更新日期:2012-09-01 00:00:00

  • Beta-adrenergic receptor blockade modulates Bcl-X(S) expression and reduces apoptosis in failing myocardium.

    abstract::The mechanisms by which beta-adrenergic receptor (beta-AR) blockade modulates apoptosis in heart failure (HF) are unclear. We examined the impact of beta-AR blockade with metoprolol on myocardial remodeling, apoptosis, pro-apoptotic (Fas, Fas ligand, Bax, and Bcl-X(S)) and anti-apoptotic (Bcl-X(L)and Bcl-2) gene expre...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(03)00052-x

    authors: Prabhu SD,Wang G,Luo J,Gu Y,Ping P,Chandrasekar B

    更新日期:2003-05-01 00:00:00

  • Redox regulation of cardiac hypertrophy.

    abstract::It is increasingly evident that redox-dependent modifications in cellular proteins and signaling pathways (or redox signaling) play important roles in many aspects of cardiac hypertrophy. Indeed, these redox modifications may be intricately linked with the process of hypertrophy wherein there is not only a significant...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2014.02.002

    authors: Sag CM,Santos CX,Shah AM

    更新日期:2014-08-01 00:00:00

  • Decreased susceptibility of contractile function to hypoxia/reoxygenation in chronic infarcted rat hearts.

    abstract::Cardiac hypertrophy is associated with modifications in Ca2+ transport processes, enzymes of energy metabolism and antioxidant capacity. It is unknown whether these changes occur in infarct-induced hypertrophy with regard to an altered susceptibility to ischemia/reperfusion injury. We examined changes in sarcoplasmic ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1998.0794

    authors: Wagner KD,Geil D,Schimke I,Stauss HM,Lammerich A,Theres H,Pfitzer G,Vetter R,Günther J

    更新日期:1998-11-01 00:00:00