Role of protein kinase C in mitochondrial KATP channel-mediated protection against Ca2+ overload injury in rat myocardium.

Abstract:

:Growing evidence exists that ATP-sensitive mitochondrial potassium channels (MitoKATP channel) are a major contributor to the cardiac protection against ischemia. Given the importance of mitochondria in the cardiac cell, we tested whether the potent and specific opener of the MitoKATP channel diazoxide attenuates the lethal injury associated with Ca2+overload. The specific aims of this study were to test whether protection by diazoxide is mediated by MitoKATP channels; whether diazoxide mimics the effects of Ca2+ preconditioning; and whether diazoxide reduces Ca2+ paradox (PD) injury via protein kinase C (PKC) signaling pathways. Langendorff-perfused rat hearts were subjected to the Ca2+ PD (10 minutes of Ca2+ depletion followed by 10 minutes of Ca2+ repletion). The effects of the MitoKATP channel and other interventions on functional, biochemical, and pathological changes in hearts subjected to Ca2+ PD were assessed. In hearts treated with 80 micromol/L diazoxide, left ventricular end-diastolic pressure and coronary flow were significantly preserved after Ca2+ PD; peak lactate dehydrogenase release was also significantly decreased, although ATP content was less depleted. The cellular structures were well preserved, including mitochondria and intercalated disks in diazoxide-treated hearts compared with nontreated Ca2+ PD hearts. The salutary effects of diazoxide on the Ca2+ PD injury were similar to those in hearts that underwent Ca2+ preconditioning or pretreatment with phorbol 12-myristate 13-acetate before Ca2+ PD. The addition of sodium 5-hydroxydecanoate, a specific MitoKATP channel inhibitor, or chelerythrine chloride, a PKC inhibitor, during diazoxide pretreatment completely abolished the beneficial effects of diazoxide on the Ca2+ PD. Blockade of Ca2+ entry during diazoxide treatment by inhibiting L-type Ca2+ channel with verapamil or nifedipine also completely reversed the beneficial effects of diazoxide on the Ca2+ PD. PKC-delta was translocated to the mitochondria, intercalated disks, and nuclei of myocytes in diazoxide-pretreated hearts, and PKC-alpha and PKC-epsilon were translocated to sarcolemma and intercalated disks, respectively. This study suggests that the effect of the MitoKATP channel is mediated by PKC-mediated signaling pathway.

journal_name

Circ Res

journal_title

Circulation research

authors

Wang Y,Ashraf M

doi

10.1161/01.res.84.10.1156

subject

Has Abstract

pub_date

1999-05-28 00:00:00

pages

1156-65

issue

10

eissn

0009-7330

issn

1524-4571

journal_volume

84

pub_type

杂志文章
  • A dynamic model of the cardiac ventricular action potential. II. Afterdepolarizations, triggered activity, and potentiation.

    abstract::The action potential model presented in our accompanying article in this journal is used to investigate phenomena that involve dynamic changes of [Ca2+]i, as described below. Delayed afterdepolarizations (DADs) are induced by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR), which, in turn, activates both...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.74.6.1097

    authors: Luo CH,Rudy Y

    更新日期:1994-06-01 00:00:00

  • Effects of cytosolic ATP on Ca(2+) sparks and SR Ca(2+) content in permeabilized cardiac myocytes.

    abstract::Confocal imaging was used to study the influence of cytosolic ATP on the properties of spontaneous Ca(2+) sparks in permeabilized ventricular myocytes. Cells were perfused with mock intracellular solutions containing fluo 3. Reducing [ATP] to <0.5 mmol/L decreased the frequency but increased the amplitude of spontaneo...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/hh1801.096264

    authors: Yang Z,Steele DS

    更新日期:2001-09-14 00:00:00

  • Interaction of capillary, interstitial, and lymphatic forces in the canine hindpaw.

    abstract::We used plethysmograph techniques to measure or calculate the tissue and capillary forces and flows (capillary pressure, tissue and plasma oncotic pressure, transcapillary pressure drop, lymph flow, and interstitial pressure) in a dog hindpaw preparation in situ at three different venous pressures (PV). Since lymph wa...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.39.2.245

    authors: Chen HI,Granger HJ,Taylor AE

    更新日期:1976-08-01 00:00:00

  • Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing.

    abstract:RATIONALE:Individuals with naturally occurring loss-of-function proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations experience reduced low-density lipoprotein cholesterol levels and protection against cardiovascular disease. OBJECTIVE:The goal of this study was to assess whether genome editing using a clus...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.115.304351

    authors: Ding Q,Strong A,Patel KM,Ng SL,Gosis BS,Regan SN,Cowan CA,Rader DJ,Musunuru K

    更新日期:2014-08-15 00:00:00

  • Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle.

    abstract::The mechanical properties of mammalian ventricular cardiac muscle have been studied in the presence and in the absence of an intact endocardial surface. Isotonic and isometric twitch contractions were obtained from papillary muscles of the right ventricle of cat at 29 degrees and 37 degrees C, at different extracellul...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.62.2.358

    authors: Brutsaert DL,Meulemans AL,Sipido KR,Sys SU

    更新日期:1988-02-01 00:00:00

  • Hirudin and nitrates inhibit the thrombin-induced release of endothelin from the intact porcine aorta.

    abstract::In intact porcine aorta, endothelium-derived nitric oxide released on thrombin stimulation inhibits the concomitant production of endothelin. Experiments were designed to examine the effect of hirudin (which inactivates thrombin) and the nitrovasodilators nitroglycerin and 3-morpholinosydnonimine on the spontaneous an...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.6.1768

    authors: Boulanger CM,Lüscher TF

    更新日期:1991-06-01 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

  • Cholinergic constriction in the general circulation and its role in coronary artery spasm.

    abstract::The release of acetylcholine from autonomic nerves in those tissues that receive a cholinergic innervation is widely believed to dilate blood vessels. Exogenously administered acetylcholine in vivo does dilate vascular beds and produce hypotension; however, this latter effect is indirect and probably the result of lib...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.res.65.2.237

    authors: Kalsner S

    更新日期:1989-08-01 00:00:00

  • Functional roles of a Ca2+-activated K+ channel in atrioventricular nodes.

    abstract::Since the first description of the anatomical atrioventricular nodes (AVNs), a large number of studies have provided insights into the heterogeneity of the structure as well as a repertoire of ion channel proteins that govern this complex conduction pathway between the atria and ventricles. These studies have revealed...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.107.161778

    authors: Zhang Q,Timofeyev V,Lu L,Li N,Singapuri A,Long MK,Bond CT,Adelman JP,Chiamvimonvat N

    更新日期:2008-02-29 00:00:00

  • Identification of receptor binding and activation sites in endothelin-1 by use of site-directed mutagenesis.

    abstract::This study addresses the structural requirements for the intracellular processing and receptor binding properties of endothelin-1 (ET-1). Point mutants of preproendothelin-1 cDNA, with replacement of the codons for Lys9 of ET-1 by ones for Ala and Glu and of Ile20 and Trp21 by ones encoding Ala, were expressed in COS-...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.77.6.1087

    authors: Ergul A,Tackett RL,Puett D

    更新日期:1995-12-01 00:00:00

  • Cardiac-specific ablation of G-protein receptor kinase 2 redefines its roles in heart development and beta-adrenergic signaling.

    abstract::G-protein receptor kinase 2 (GRK2) is 1 of 7 mammalian GRKs that phosphorylate ligand-bound 7-transmembrane receptors, causing receptor uncoupling from G proteins and potentially activating non-G-protein signaling pathways. GRK2 is unique among members of the GRK family in that its genetic ablation causes embryonic le...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000247932.71270.2c

    authors: Matkovich SJ,Diwan A,Klanke JL,Hammer DJ,Marreez Y,Odley AM,Brunskill EW,Koch WJ,Schwartz RJ,Dorn GW 2nd

    更新日期:2006-10-27 00:00:00

  • Simulated blood flow and the effects on prostacyclin production in the dog femoral artery.

    abstract::Effects of blood flow on the production of prostacyclin (PGI2) were examined in the canine femoral artery perfused ex vivo. Each artery was perfused in situ with medium 199, under conditions of simulated blood flow. To simulate the normal and abnormal blood flow waveforms at the same mean flow rate, we developed a flo...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.4.1095

    authors: Onohara T,Okadome K,Yamamura S,Mii S,Sugimachi K

    更新日期:1991-04-01 00:00:00

  • Calcium, its role in isoproterenol-stimulated atrial natriuretic peptide secretion by superfused rat atria.

    abstract::The beta-adrenergic agonist isoproterenol stimulates immunoreactive atrial natriuretic peptide (IR-ANP) secretion by superfused rat atria in vitro. beta-Adrenergic agonists alter the cellular handling of calcium, which culminates in a rise in the systolic calcium concentration. This is achieved by increasing calcium i...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.65.3.600

    authors: Schiebinger RJ

    更新日期:1989-09-01 00:00:00

  • Effects of quinapril, a new angiotensin converting enzyme inhibitor, on left ventricular failure and survival in the cardiomyopathic hamster. Hemodynamic, morphological, and biochemical correlates.

    abstract::The effect of chronic therapy with quinapril on the temporal progression of left ventricular failure and survival was assessed in the CHF 146 cardiomyopathic (CM) hamster, which is an idiopathic model of congestive heart failure. Age-matched Golden Syrian (GS) hamsters served as normal controls. Quinapril was administ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.5.1302

    authors: Haleen SJ,Weishaar RE,Overhiser RW,Bousley RF,Keiser JA,Rapundalo SR,Taylor DG

    更新日期:1991-05-01 00:00:00

  • Developmental changes in the sensitivity of the chick embryo ventricle to beta-adrenergic agonist during adrenergic innervation.

    abstract::As early as the 4th embryonic day, the ventricle of the chick embryo responded to isoproterenol (Iso) with an increase in the force of contraction; at all ages studied, this positive inotropic effect was accompanied by an increased rate of tension development. There was a transient, 10-fold decrease in the sensitivity...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.48.2.245

    authors: Higgins D,Pappano AJ

    更新日期:1981-02-01 00:00:00

  • The mechanism of flecainide action in CPVT does not involve a direct effect on RyR2.

    abstract:RATIONALE:Flecainide, a class 1c antiarrhythmic, has emerged as an effective therapy in preventing arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) refractory to β-adrenergic receptor blockade. It has been proposed that the clinical efficacy of flecainide in CPVT is because of t...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.116.305347

    authors: Bannister ML,Thomas NL,Sikkel MB,Mukherjee S,Maxwell C,MacLeod KT,George CH,Williams AJ

    更新日期:2015-04-10 00:00:00

  • Arterial Stiffness Preceding Diabetes: A Longitudinal Study.

    abstract:RATIONALE:Previous studies on the relationship between diabetes and arterial stiffness were mostly cross-sectional. A few longitudinal studies focused on one single direction. Whether the association between arterial stiffness and diabetes is bidirectional remains unclear to date. OBJECTIVE:To explore the temporal rel...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.120.317950

    authors: Zheng M,Zhang X,Chen S,Song Y,Zhao Q,Gao X,Wu S

    更新日期:2020-12-04 00:00:00

  • Comparison of the effects of different inotropic interventions on force, velocity, and power in rabbit myocardium.

    abstract::To gain some insight into inotropic mechanisms, we compared the effects of several classes of inotropic interventions on the isometric twitch and force-velocity properties of isolated rabbit myocardium. Postextrasystolic potentiation was chosen as one of the interventions in the belief that its onset is so rapid that ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.65.5.1161

    authors: Chiu YC,Walley KR,Ford LE

    更新日期:1989-11-01 00:00:00

  • Late-systolic pumping properties of the left ventricle. Deviation from elastance-resistance behavior.

    abstract::Elastance-resistance [E(t)-R] representations of the left ventricle (LV) were evaluated for their ability to reproduce instantaneous pressure [P(t)] and outflow [Q(t)]. Experiments were performed in open-chest rats. P(t) and Q(t) were measured during steady-state ejecting beats and during a beat in which the aorta was...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.66.1.218

    authors: Campbell KB,Kirkpatrick RD,Knowlen GG,Ringo JA

    更新日期:1990-01-01 00:00:00

  • Lidocaine-induced Brugada syndrome phenotype linked to a novel double mutation in the cardiac sodium channel.

    abstract::Brugada syndrome has been linked to mutations in SCN5A. Agents that dissociate slowly from the sodium channel such as flecainide and ajmaline unmask the Brugada syndrome electrocardiogram and precipitate ventricular tachycardia/fibrillation. Lidocaine, an agent with rapid dissociation kinetics, has previously been sho...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.108.172619

    authors: Barajas-Martínez HM,Hu D,Cordeiro JM,Wu Y,Kovacs RJ,Meltser H,Kui H,Elena B,Brugada R,Antzelevitch C,Dumaine R

    更新日期:2008-08-15 00:00:00

  • Thin filament disinhibition by restrictive cardiomyopathy mutant R193H troponin I induces Ca2+-independent mechanical tone and acute myocyte remodeling.

    abstract::Inherited restrictive cardiomyopathy (RCM) is a debilitating disease characterized by a stiff heart with impaired ventricular relaxation. Mutations in cardiac troponin I (cTnI) were identified as causal for RCM. Acute genetic engineering of adult cardiac myocytes was used to identify primary structure/function effects...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000268412.34364.50

    authors: Davis J,Wen H,Edwards T,Metzger JM

    更新日期:2007-05-25 00:00:00

  • Selective antagonism of hormone-induced vasoconstriction by synthetic atrial natriuretic factor in the rat microcirculation.

    abstract::Synthetic atrial natriuretic factor (ANF) was either added to suffusate solutions (30 nM) or infused into the jugular vein (0.1 nanomol/min/100 g) of anesthetized rats. Steady-state blood flow was calculated from arteriolar diameter and red blood cell velocity measurements using video microscopy in the intestinal or s...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.61.1.42

    authors: Proctor KG,Bealer SL

    更新日期:1987-07-01 00:00:00

  • An isolated cardiac conduction disease maps to chromosome 19q.

    abstract::Isolated cardiac conduction disease is an autosomal dominant defect that includes various combinations of bundle branch or fascicular blocks. These defects can cause sudden death due to a complete heart block. We used a genome-wide screening approach with polymorphic (CA)n repeat markers to determine the chromosomal p...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.77.4.735

    authors: de Meeus A,Stephan E,Debrus S,Jean MK,Loiselet J,Weissenbach J,Demaille J,Bouvagnet P

    更新日期:1995-10-01 00:00:00

  • Cytosolic alkalinization of vascular endothelial cells produced by an abrupt reduction in fluid shear stress.

    abstract::Reductions in fluid shear stress produce endothelium-dependent vasoconstriction and promote neointimal hyperplasia, but the intracellular signaling mechanisms involved in these processes are poorly understood. To examine whether decreases in fluid shear stress affect endothelial cytosolic pH, carboxy-seminaphthorhodaf...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.82.7.803

    authors: Ziegelstein RC,Blank PS,Cheng L,Capogrossi MC

    更新日期:1998-04-20 00:00:00

  • A new protocol for removal of the endothelium from the perfused rat hind-limb preparation.

    abstract::A new protocol has been developed for selective removal of the endothelium from the arteries of the perfused rat hind-limb preparation. The hind limb was perfused with oxygenated Krebs-Ringer bicarbonate solution with a combination of high flow and timed air bubbles (2 minutes at high flow followed by 5 minutes of air...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.64.6.1190

    authors: Ralevic V,Kristek F,Hudlická O,Burnstock G

    更新日期:1989-06-01 00:00:00

  • Cardiac sodium-calcium exchanger is regulated by allosteric calcium and exchanger inhibitory peptide at distinct sites.

    abstract::The sarcolemmal Na+-Ca2+ exchanger (NCX) is the main Ca2+ extrusion mechanism in cardiac myocytes and is thus essential for the regulation of Ca2+ homeostasis and contractile function. A cytosolic region (f-loop) of the protein mediates regulation of NCX function by intracellular factors including inhibition by exchan...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000151334.48676.68

    authors: Maack C,Ganesan A,Sidor A,O'Rourke B

    更新日期:2005-01-07 00:00:00

  • High-density lipoprotein: vascular protective effects, dysfunction, and potential as therapeutic target.

    abstract::High-density lipoprotein (HDL) is a complex mixture of lipoproteins that is associated with many minor proteins and lipids that influence the function of HDL. Although HDL is a promising marker and potential therapeutic target based on its epidemiological data and the effects of healthy HDL in vitro in endothelial cel...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.114.300935

    authors: Lüscher TF,Landmesser U,von Eckardstein A,Fogelman AM

    更新日期:2014-01-03 00:00:00

  • Role for tissue factor pathway in murine model of vascular remodeling.

    abstract::Tissue factor (TF) is a low-molecular-weight glycoprotein that initiates the extrinsic clotting cascade and is considered a major regulator of arterial thrombogenicity. TF pathway inhibitor (TFPI) is a major physiological inhibitor of TF-initiated coagulation. The aim of this study was to define the complex interplay ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/hh1301.092508

    authors: Singh R,Pan S,Mueske CS,Witt T,Kleppe LS,Peterson TE,Slobodova A,Chang JY,Caplice NM,Simari RD

    更新日期:2001-07-06 00:00:00

  • Dual effects of norepinephrine and mechanisms of baroreceptor stimulation.

    abstract::The aim of this study was to determine the mechanism of action of norepinephrine (NE) on arterial baroreceptors (BRs), with the focus on regularly discharging, presumably myelinated fibers. With the use of an in vitro aortic arch/aortic nerve preparation from rats, BR single-fiber discharge was recorded simultaneously...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.61.3.409

    authors: Munch PA,Thoren PN,Brown AM

    更新日期:1987-09-01 00:00:00

  • Phorbol diester modulates alpha-adrenergic receptor-coupled calcium efflux and alpha-adrenergic receptor number in cultured vascular smooth muscle cells.

    abstract::The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate was used to probe the role of protein kinase-C in the modulation of alpha-adrenergic receptor-coupled calcium efflux in cultured vascular smooth muscle cells derived from rabbit aorta. Exposure of cells to 12-O-tetradecanoyl phorbol-13-acetate for 6 minutes cause...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.58.3.393

    authors: Colucci WS,Gimbrone MA Jr,Alexander RW

    更新日期:1986-03-01 00:00:00