Effects of protein kinase C inhibitors in in situ and isolated ischemic rabbit myocardium.

Abstract:

:We tested the effects of the protein kinase C (PKC) inhibitors bisindolylmaleimide (1 microM) and chelerythrine (2 microM) on myocardial ischemia-reperfusion injury in in situ and isolated perfused rabbit hearts. In non-ischemic isolated hearts, bisindolylmaleimide (1 microM) and chelerythrine (2 microM) blocked sn-1,2-dioctanoylglycerol (DOG)-induced coronary vasoconstriction by approximately 80%. Intact hearts were subjected to 45 min coronary artery occlusion and 2 h reperfusion. Infarct size, determined by triphenyltetrazolium chloride (TTC)-staining and expressed as percentage of risk area, was reduced approximately 50% by both bisindolylmaleimide (0.05 mg/kg, i.v.) and chelerythrine (0.1 mg/kg, i.v.) compared to vehicle treated controls. In contrast, a higher dose of chelerythrine (3.8 mg/kg, i.v.) did not significantly reduce infarct size. Isolated hearts were subjected to 45 min of global normothermic (37 degrees C) ischemia and 60 min reperfusion. Control hearts exhibited 45+/-2% recovery of pre-ischemic left ventricular developed pressure (LVDP) compared to bisindolylmaleimide- (73+/-7%) and chelerythrine-treated hearts (70+/-11%). Bisindolylmaleimide and cherythrine reduced infarct size from a control value of 24+/-4 to 8+/-2 and 9+/-3%, respectively. Preconditioning isolated hearts with 5 min ischemia and 10 min reperfusion prior to prolonged ischemia reduced infarct size to 10.4+/-2.3%, an effect which was blocked by chelerythrine (22.5+/-4.2% infarct size). These results suggest that although PKC may play a role in ischemic preconditioning, PKC inhibitors can be cardioprotective during prolonged ischemia.

journal_name

J Mol Cell Cardiol

authors

Lasley RD,Noble MA,Mentzer RM Jr

doi

10.1006/jmcc.1997.0559

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

3345-56

issue

12

eissn

0022-2828

issn

1095-8584

pii

S0022282897905599

journal_volume

29

pub_type

杂志文章
  • Heart estrogen receptor alpha: distinct membrane and nuclear distribution patterns and regulation by estrogen.

    abstract::Estrogen receptor alpha (ERalpha) is present in the heart consistent with estrogen-induced modulation of cardiac function by genomic and non-genomic mechanisms, and with estrogen-mediated cardioprotective effects. We show that, in heart from adult male rats, ERalpha is detected mainly as two distinct isoforms: (i) a a...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2006.05.022

    authors: Ropero AB,Eghbali M,Minosyan TY,Tang G,Toro L,Stefani E

    更新日期:2006-09-01 00:00:00

  • Metabolic inhibition activates a non-selective current through connexin hemichannels in isolated ventricular myocytes.

    abstract::Intracellular Na(+)accumulation and K(+)loss play important roles in the pathogenesis of arrhythmias and injury in the ischemic heart. We investigated the role of metabolically sensitive connexin hemichannels as a potential route for Na(+)influx and K(+)efflux during ischemia, using dye uptake and electrophysiological...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2000.1220

    authors: Kondo RP,Wang SY,John SA,Weiss JN,Goldhaber JI

    更新日期:2000-10-01 00:00:00

  • Cobra venom cardiotoxin induces perturbations of cytosolic calcium homeostasis and hypercontracture in adult rat ventricular myocytes.

    abstract::The effects of Cobra venom cardiotoxin (CTX) on the cellular morphology, twitch amplitude and intracellular calcium ([Ca2+]i) of the ventricular myocytes were studied. [Ca2+]i and twitch amplitude were determined with a fluorometric ratio method using Fura-2/AM and Calcium Green-1 as calcium indicators, and a videomic...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1997.0511

    authors: Wang HX,Lau SY,Huang SJ,Kwan CY,Wong TM

    更新日期:1997-10-01 00:00:00

  • In vivo expression of a conditional TGF-beta1 transgene: no evidence for TGF-beta1 transgene expression in SM22alpha-tTA transgenic mice.

    abstract::Transforming growth beta-1 (TGF-beta1) appears to play a critical role in the regulation of arterial intimal growth and the development of atherosclerosis. TGF-beta1 is expressed at increased levels in diseased arteries; however, its role in disease development remains controversial. Experiments in which TGF-beta1 is ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2005.09.015

    authors: Lee S,Agah R,Xiao M,Frutkin AD,Kremen M,Shi H,Dichek DA

    更新日期:2006-01-01 00:00:00

  • Molecular nature and regulation of the mitochondrial permeability transition pore(s), drug target(s) in cardioprotection.

    abstract::The mitochondrial permeability transition, an established mechanism for heart diseases, is a long-standing mystery of mitochondrial biology and a prime drug target for cardioprotection. Several hypotheses about its molecular nature have been put forward over the years, and the prevailing view is that permeabilization ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2020.05.014

    authors: Carraro M,Carrer A,Urbani A,Bernardi P

    更新日期:2020-07-01 00:00:00

  • Phenylephrine preconditioning involves modulation of cardiac sarcolemmal K(ATP) current by PKC delta, AMPK and p38 MAPK.

    abstract::Preconditioning of hearts with the α(1)-adrenoceptor agonist phenylephrine decreases infarct size and increases the functional recovery of the heart following ischaemia-reperfusion. However, the cellular mechanisms responsible for this protection are not known. We investigated the role of protein kinase C ε and δ (PKC...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2011.06.015

    authors: Turrell HE,Rodrigo GC,Norman RI,Dickens M,Standen NB

    更新日期:2011-09-01 00:00:00

  • Inhibition of angiotensin-converting enzyme increases the nitric oxide levels in canine ischemic myocardium.

    abstract::Since angiotensin-converting enzyme (ACE) produces angiotensin II in the heart, ACE inhibitors may prevent coronary vasoconstriction and increase coronary blood flow. On the other hand, since ACE inhibitors also inhibit kininase II which results in reduced degradation of bradykinin, ACE inhibitors may increase cardiac...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1998.0806

    authors: Kitakaze M,Node K,Minamino T,Asanuma H,Ueda Y,Kosaka H,Kuzuya T,Hori M

    更新日期:1998-11-01 00:00:00

  • Regulation of L-type calcium channels of vascular smooth muscle cells.

    abstract::Vascular tone is regulated by a variety of neurotransmitters, vasoactive hormones and autacoids, and vasoactive drugs. These actions are mediated, at least in part, by actions on the membrane ion channels, exerted either directly or indirectly. In this article, we described evidence that four different protein kinase ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/s0022-2828(08)80009-0

    authors: Xiong Z,Sperelakis N

    更新日期:1995-01-01 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

    doi:10.1006/jmcc.1996.0095

    authors: Solem LE,Heller LJ,Wallace KB

    更新日期:1996-05-01 00:00:00

  • Epitope mapping of mitochondrial adenine nucleotide translocase-1 in idiopathic dilated cardiomyopathy.

    abstract::Mitochondrial adenine nucleotide translocase (ANT) is a specific target for the autoantibody response in idiopathic dilated cardiomyopathy (IDCM). We have undertaken an epitope analysis of ANT in IDCM by immunoblot with recombinant GST-ANT fusion proteins and with cellulose-bound decapeptides of human ANT1. Forty-five...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2002.1538

    authors: Manchado C,Orús J,Villarroya F,Roig E,Heras M,Giralt M,Iglesias R,Sanz G,Mampel T,Viñas O

    更新日期:2002-05-01 00:00:00

  • Alterations in heart membrane calcium transport during the development of ischemia-reperfusion injury.

    abstract::Global ischemia in guinea-pig hearts for 60 to 90 min depressed microsomal and mitochondrial Ca2+ uptake activities. Reperfusion of the 60 min ischemic hearts resulted in incomplete recovery of contractile function and calcium uptake activities of both mitochondrial and microsomal fractions. On the other hand, reperfu...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(88)90327-6

    authors: Dhalla NS,Panagia V,Singal PK,Makino N,Dixon IM,Eyolfson DA

    更新日期:1988-03-01 00:00:00

  • Hydrophilic bile salt ursodeoxycholic acid protects myocardium against reperfusion injury in a PI3K/Akt dependent pathway.

    abstract::The opening of mitochondrial permeability transition pore (PTP) during reperfusion injury of heart has been well demonstrated and thus controlling PTP would attenuate the myocardial damage and cell death. Ursodeoxycholic acid (UDCA) is a hydrophilic bile salt and has been shown to prevent apoptosis in hepatocytes by i...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2005.07.014

    authors: Rajesh KG,Suzuki R,Maeda H,Yamamoto M,Yutong X,Sasaguri S

    更新日期:2005-11-01 00:00:00

  • Mechanistic role of the CREB-regulated transcription coactivator 1 in cardiac hypertrophy.

    abstract::The sympathetic nervous system is the main stimulator of cardiac function. While acute activation of the β-adrenoceptors exerts positive inotropic and lusitropic effects by increasing cAMP and Ca2+, chronically enhanced sympathetic tone with changed β-adrenergic signaling leads to alterations of gene expression and re...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2018.12.001

    authors: Morhenn K,Quentin T,Wichmann H,Steinmetz M,Prondzynski M,Söhren KD,Christ T,Geertz B,Schröder S,Schöndube FA,Hasenfuss G,Schlossarek S,Zimmermann WH,Carrier L,Eschenhagen T,Cardinaux JR,Lutz S,Oetjen E

    更新日期:2019-02-01 00:00:00

  • Sarcoplasmic reticulum Ca2+ pump blockade decreases O2 use of unloaded contracting rat heart slices: thapsigargin and cyclopiazonic acid.

    abstract::We previously established a new measuring method of the myocardial O2 consumption of mechanically unloaded rat left-ventricular slices. O 2 consumption of unstimulated myocardium corresponds to basal metabolism. We have found O2 consumption of stimulated myocardium to include basal metabolism and O 2 consumption for C...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1997.0630

    authors: Takaki M,Kohzuki H,Kawatani Y,Yoshida A,Ishidate H,Suga H

    更新日期:1998-03-01 00:00:00

  • Genetic modification of the heart: chaperones and the cytoskeleton.

    abstract::In the past decade, genetic modification has been extensively employed to define (patho)physiological roles of chaperones and the cytoskeleton in the heart, promoting dramatic advances in this field. Both loss-of-function and gain-of-function approaches have been used productively. alphaB-Crystallin (CryAB) is the mos...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2004.07.004

    authors: Kumarapeli AR,Wang X

    更新日期:2004-12-01 00:00:00

  • Thioredoxin and ventricular remodeling.

    abstract::Increasing bodies of evidence indicate that reactive oxygen species (ROS) produced by mitochondria and other sources play an essential role in mediating ventricular remodeling after myocardial infarction and the development of heart failure. Antioxidants scavenge ROS, thereby maintaining the reduced environment of cel...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2006.08.006

    authors: Ago T,Sadoshima J

    更新日期:2006-11-01 00:00:00

  • Induction of cardiac beta-adrenergic receptor kinase 1 in rat heart failure caused by coronary ligation.

    abstract::Beta-adrenergic receptor kinase 1 (beta ARK1) participates in the desensitization of beta-adrenergic receptors by uncoupling the signal transduction. The present study was designed to examine whether neurohumoral increase is crucial for the activation of beta ARK1 in heart failure. Four weeks after the ligation of rat...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1999.0958

    authors: Ishigai Y,Mori T,Moriyama S,Shibano T

    更新日期:1999-06-01 00:00:00

  • Ca(2+) influx through L-type Ca(2+) channels and transient receptor potential channels activates pathological hypertrophy signaling.

    abstract::Common cardiovascular diseases such as hypertension and myocardial infarction require that myocytes develop greater than normal force to maintain cardiac pump function. This requires increases in [Ca(2+)]. These diseases induce cardiac hypertrophy and increases in [Ca(2+)] are known to be an essential proximal signal ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2012.08.005

    authors: Gao H,Wang F,Wang W,Makarewich CA,Zhang H,Kubo H,Berretta RM,Barr LA,Molkentin JD,Houser SR

    更新日期:2012-11-01 00:00:00

  • Late preconditioning elicited by activation of adenosine A(3) receptor in heart: role of NF- kappa B, iNOS and mitochondrial K(ATP) channel.

    abstract::Activation of adenosine A(3) receptor (A(3)AR) protects against ischemia/reperfusion injury in the heart. However, the downstream signaling mechanisms leading to its delayed anti-ischemic effects remain unclear. We hypothesized that A(3)AR stimulation protects the heart via activation of nuclear transcription factor k...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2001.1510

    authors: Zhao TC,Kukreja RC

    更新日期:2002-03-01 00:00:00

  • Measurement of electrically-induced Ca2+ transients in Quin2-loaded cardiac myocytes.

    abstract::Quin2 is a fluorescent Ca2+-sensitive indicator which in its acetoxymethyl ester form can be loaded into the cytosolic compartment of cells without any disruption of the plasma membrane. Quin2 has been used with many cell types to measure changes of [Ca2+]i in response to hormones and other stimuli. In this report we ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(86)80919-1

    authors: Thomas AP,Selak M,Williamson JR

    更新日期:1986-05-01 00:00:00

  • Angiotensin II requires an intact cardiac thyrotropin-releasing hormone (TRH) system to induce cardiac hypertrophy in mouse.

    abstract::Cardiac tyhrotropin-releasing hormone (TRH) is overexpressed in the hypertrophied left ventricle (LV) of spontaneously hypertensive rats (SHR) and its inhibition prevents both hypertrophy and fibrosis. In a normal heart, the TRH increase induces fibrosis and hypertrophy opening the question of whether TRH could be a c...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2018.09.009

    authors: Peres Diaz LS,Schuman ML,Aisicovich M,Toblli JE,Pirola CJ,Landa MS,García SI

    更新日期:2018-11-01 00:00:00

  • Mechanism of cardioprotection following trauma-hemorrhagic shock by a selective estrogen receptor-beta agonist: up-regulation of cardiac heat shock factor-1 and heat shock proteins.

    abstract::Although 17beta-estradiol (E2) administration following trauma-hemorrhage (T-H) improves cardiac function in male rodents, it is not known whether the salutary effects of E2 are mediated via estrogen receptor (ER)-alpha or ER-beta, and whether cardiac heat shock proteins (Hsp) are affected by E2 administration. Male S...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2005.10.001

    authors: Yu HP,Shimizu T,Choudhry MA,Hsieh YC,Suzuki T,Bland KI,Chaudry IH

    更新日期:2006-01-01 00:00:00

  • Rare non-coding Desmoglein-2 variant contributes to Arrhythmogenic right ventricular cardiomyopathy.

    abstract::Arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to variants in the coding sequence of desmosomal genes. The potential contribution of non-coding desmoglein-2 (DSG2) variants for development of ARVC is undescribed. We sequenced 1450 base pairs upstream of ATG in the DSG2 gene in 65 unrelated pati...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2019.04.029

    authors: Christensen AH,Andersen CB,Wassilew K,Svendsen JH,Bundgaard H,Brand SM,Schmitz B

    更新日期:2019-06-01 00:00:00

  • Rational design of a selective antagonist of epsilon protein kinase C derived from the selective allosteric agonist, pseudo-RACK peptide.

    abstract::We have previously shown that domains involved in binding of protein kinase C (PKC) isozymes to their respective anchoring proteins (RACKs) and short peptides derived from these domains are PKC isozyme-selective antagonists. We also identified PKC isozyme-selective agonists, named psiRACK peptides, derived from a sequ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2007.01.007

    authors: Liron T,Chen LE,Khaner H,Vallentin A,Mochly-Rosen D

    更新日期:2007-04-01 00:00:00

  • Production of free radicals and lipid peroxides in early experimental myocardial ischemia.

    abstract::Free radicals and lipid peroxides have recently been identified by us [1, 2, 3] as metabolic intermediates during acute myocardial ischemia. The mechanisms by which evolving myocardial ischemia initiates free radical production are not clear. Based on studies in vitro, it is feasible to consider the following possibil...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(83)90260-2

    authors: Rao PS,Cohen MV,Mueller HS

    更新日期:1983-10-01 00:00:00

  • A phenotypic screen to identify hypertrophy-modulating microRNAs in primary cardiomyocytes.

    abstract::MicroRNAs (miRNAs) are small non-coding RNAs that control expression of complementary target mRNAs. A growing number of miRNAs has been implicated in the pathogenesis of cardiac diseases, mostly based not on functional data, but on the observation that they are dysregulated in diseased myocardium. Consequently, our kn...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2011.07.010

    authors: Jentzsch C,Leierseder S,Loyer X,Flohrschütz I,Sassi Y,Hartmann D,Thum T,Laggerbauer B,Engelhardt S

    更新日期:2012-01-01 00:00:00

  • Cytochalasin D alters kinetics of Ca2+ transient in rat ventricular cardiomyocytes: an effect of altered actin cytoskeleton?

    abstract::The effects of cytochalasin D, a specific F-actin depolymerizing agent, on Ca2+ transients in rat ventricular cardiomyocytes were investigated. Cytochalasin D (20 microM) significantly slowed decay of Ca2+ transients (tau decay control cells=28.1+/-1.3, n=28tau decay=47.3+/-2.8 ms, n=20, P<0.001). The rising phase of ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1998.0715

    authors: Undrovinas AI,Maltsev VA

    更新日期:1998-08-01 00:00:00

  • Oxygen diffusion distance in thyroxine-induced hypertrophic rabbit myocardium.

    abstract::We studied the oxygen diffusion distance in the rabbit myocardium in untreated animals and in animals treated with thyroxine (T4) for 3 days and 16 days. The subepicardial and subendocardial regions were studied separately. Sixteen days of T4 treatment results in significant cardiac hypertrophy. After 16 days, the per...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(88)80146-9

    authors: Seiden D,Navidad P,Weiss HR

    更新日期:1988-10-01 00:00:00

  • Serine/Threonine Phosphatases in Atrial Fibrillation.

    abstract::Serine/threonine protein phosphatases control dephosphorylation of numerous cardiac proteins, including a variety of ion channels and calcium-handling proteins, thereby providing precise post-translational regulation of cardiac electrophysiology and function. Accordingly, dysfunction of this regulation can contribute ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2016.12.009

    authors: Heijman J,Ghezelbash S,Wehrens XH,Dobrev D

    更新日期:2017-02-01 00:00:00

  • Regulation of mTOR and S6K1 activation by the nPKC isoforms, PKCepsilon and PKCdelta, in adult cardiac muscle cells.

    abstract::Activation of both mTOR and its downstream target, S6K1 (p70 S6 kinase) have been implicated to affect cardiac hypertrophy. Our earlier work, in a feline model of 1-48 h pressure overload, demonstrated that mTOR/S6K1 activation occurred primarily through a PKC/c-Raf pathway. To further delineate the role of specific P...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2007.09.015

    authors: Moschella PC,Rao VU,McDermott PJ,Kuppuswamy D

    更新日期:2007-12-01 00:00:00