Abstract:
:Previous work suggests that delayed protection against infarction following ischaemic preconditioning of rabbit myocardium may involve the activation of protein kinase C (PKC). Preconditioning in the presence of chelerythrine, an inhibitor of PKC, abolished the late anti-infarct effect of preconditioning. In the studies described here, we tested the hypothesis that direct PKC activation with an analogue of diacylglycerol, the physiological activator of PKC, would invoke an adaptive mechanism leading to enhanced myocardial tolerance to ischaemia 24 h later. Rabbits were treated with i.v. injections of 1,2-dioctanoyl-sn-glycerol (DiC8) 5 mg/kg or 15 mg/kg or an equivalent volume of vehicle solution. Twenty-four h after pretreatment, the animals were anaesthetised and underwent 30 min coronary artery occlusion with 120 min reperfusion. Infarct size was determined by triphenyltetrazolium staining. In vehicle pretreated rabbits, infarct-risk zone ratio was 32.8+/-2.6%. Pretreatment with DiC8 5 mg/kg did not significantly affect infarct size (26.3+/-4.0%), but pretreatment with DiC8 15 mg/kg resulted in a marked reduction in infarct size (18.0+/-3.4%, P<0.05, 1-way ANOVA). Reduction in infarct size with the higher dose of DiC8 was independent of myocardial risk zone size and systemic haemodynamic parameters during coronary occlusion. The haemodynamic effects of acute administration of DiC8 15 mg/kg were examined in a separate cohort of pentobarbitone-anaesthetised rabbits. The compound was found not to affect systolic blood pressure or heart rate under these conditions. We examined the possibility that increased ischaemic tolerance might be due to induction of the 27 and 72 kDa heat shock proteins (hsp27 and hsp70i) which are known to be cytoprotective and are upregulated by ischaemia and other stressful stimuli. Western blot analysis of left ventricular tissue revealed that neither protein was induced 24 h after treatment with DiC8 15 mg/kg. Thus, infarct limitation 24 h after DiC8 treatment did not appear to be due to increased tissue content of these proteins. The mechanisms of DiC8-induced delayed myocardial protection remain unclear. However, these data are compatible with the hypothesis that activation of PKC isoenzymes is an important intermediate signal of sub-acute cellular adaptation, and results in enhanced tolerance to ischaemia-reperfusion injury in myocardium many hours later.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Baxter GF,Mocanu MM,Yellon DMdoi
10.1006/jmcc.1997.0436subject
Has Abstractpub_date
1997-07-01 00:00:00pages
1967-75issue
7eissn
0022-2828issn
1095-8584pii
S0022-2828(97)90436-3journal_volume
29pub_type
杂志文章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
更新日期:2002-04-01 00:00:00
abstract::Cardiac connexin 43 (Cx43), Cx40 and Cx45 are co-expressed at distinct ratios in myocytes. This pattern is considered a key factor in regulating the gap junction channels composition, properties and function and remains poorly understood. This work aims to correlate gap junction function with the connexin composition ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.11.008
更新日期:2015-12-01 00:00:00
abstract::Fibrillar collagens, essential for maintaining the structural integrity of the myocardium, are degraded by matrix metalloproteinase (MMP-1). In other tissues collagenolysis is an important component of wound healing. Here we examined collagen degradation in the myocardium after infarction. Collagenase activity, measur...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(05)82390-9
更新日期:1995-06-01 00:00:00
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
doi:10.1016/j.yjmcc.2014.01.015
更新日期:2014-04-01 00:00:00
abstract::The effects of the inhibition of phospholipid degradation and superoxide radical generation on prostaglandin synthesis associated with myocardial ischemia and reperfusion were studied in the isolated, in-situ pig heart model subjected to 60 mins of regional ischemia and a further 60 mins of hypothermic potassium cardi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80009-8
更新日期:1986-09-01 00:00:00
abstract::Ischemia-induced myocardial potassium loss and post-ischemic potassium reuptake was quantitated in 8 open chest pigs during control conditions and during hemodynamic alterations which have been shown to increase steady state sarcolemmal potassium fluxes. Myocardial K+ balance was continuously computed before, during a...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90673-1
更新日期:1989-12-01 00:00:00
abstract::Although the myocardium is capable of utilizing both glucose and fatty acid substrates, glucose metabolism is inhibited in the presence of fatty acid during normal perfusion conditions. Fatty acid regulation of glucose utilization in intact beating rat hearts was studied with 13C-enriched substrates and 13C and 31P NM...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90787-6
更新日期:1989-05-01 00:00:00
abstract::Understanding the inflammatory response to myocardial ischemia is an important part of achieving the elusive clinical goal of perfect myocardial protection. While it is established that estrogen affects the chronic inflammatory processes of coronary atherosclerosis, the effects of estrogen on acute myocardial proinfla...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.06.019
更新日期:2006-02-01 00:00:00
abstract::Pathological cardiac remodeling, characterized by excessive deposition of extracellular matrix proteins and cardiac hypertrophy, leads to the development of heart failure. Meprin α (Mep1a), a zinc metalloprotease, previously reported to participate in the regulation of inflammatory response and fibrosis, may also cont...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.11.015
更新日期:2020-12-08 00:00:00
abstract::Understanding the process of Ca(2+)/Mg(2+)exchange during muscle excitation and relaxation is fundamental to elucidating the mechanism of Ca(2+)-regulated muscle contraction. During the resting phase, the C-domain of cardiac troponin C may be occupied by either Ca(2+)or Mg(2+). Here, complexes of recombinant cardiac t...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2000.1174
更新日期:2000-08-01 00:00:00
abstract::Fibroblasts play a pivotal role in cardiac remodeling and the development of heart failure through the deposition of extra-cellular matrix (ECM) proteins and also by affecting cardiomyocyte growth and function. The renin-angiotensin system (RAS) is a key regulator of the cardiovascular system in health and disease and...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2010.12.003
更新日期:2011-10-01 00:00:00
abstract::This study was undertaken to evaluate the direct cardioprotective effect of trimetazidine (TMZ), an anti-anginal drug devoid of haemodynamic action, on isolated myocytes. Cultured rat ventricular myocytes were treated with the drug 16 h and 1 h before the experiments. The drug-treated cells and control cells were plac...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1116
更新日期:1994-08-01 00:00:00
abstract::We measured myosin crossbridge detachment rate and the rates of MgADP release and MgATP binding in mouse and rat myocardial strips bearing one of the two cardiac myosin heavy chain (MyHC) isoforms. Mice and rats were fed an iodine-deficient, propylthiouracil diet resulting in ~100% expression of β-MyHC in the ventricl...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.10.010
更新日期:2013-01-01 00:00:00
abstract::The E2F4-p130 transcriptional repressor complex is a cell-cycle inhibitor in mitotic cells. However, the role of E2F4/p130 in differentiated cells is largely unknown. We investigated the role of E2F4/p130 in the regulation of apoptosis in postmitotic cardiomyocytes. Here we demonstrate that E2F4 can inhibit hypoxia-in...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.09.004
更新日期:2012-12-01 00:00:00
abstract::Recently it was shown that lipopolysaccharide (LPS) impairs the pacemaker current in human atrial myocytes. It was speculated that reduced heart rate variability (HRV), typical of patients with severe sepsis, may partially be explained by this impairment. We evaluated the effect of various types of LPS on the activity...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2011.05.004
更新日期:2011-08-01 00:00:00
abstract::The sulfonylurea receptor SUR is an ATP binding cassette (ABC) protein of the ABCC/MRP family. Unlike other ABC proteins, it has no intrinsic transport function, neither active nor passive, but associates with the potassium channel proteins Kir6.1 or Kir6.2 to form the ATP-sensitive potassium (K(ATP)) channel. Within ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2004.11.030
更新日期:2005-06-01 00:00:00
abstract::Cardiac fibroblasts represent one of the most frequent cell type in the heart of rodents and humans and alterations of their phenotype have a great impact on cardiac function. Due to aging, ischemic injuries, valvular dysfunctions, hypertension and aortic stenosis, multiple signals trigger the accumulation of extracel...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2015.12.023
更新日期:2016-03-01 00:00:00
abstract::Cardiomyocytes represent one of the most useful models to conduct cardiac research. A single adult heart yields millions of cardiomyocytes, but these cells do not survive for long after isolation. We aimed to determine whether inhibition of myosin II ATPase that is essential for muscle contraction may preserve fully d...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2013.09.004
更新日期:2013-11-01 00:00:00
abstract::Oxidative stress markedly alters protein function through redox modification of sulfhydryl groups present in cysteine residues. To explore the role of redox state in modulating cardiac K+ channels, this study examined the effects of sulfhydryl modifiers on the repolarizing transient outward current (Ito) in voltage-cl...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2002.2112
更新日期:2002-12-01 00:00:00
abstract::Fibroblast growth factor-2 (FGF-2), administered to the isolated rat heart by perfusion and under constant pressure, is protective against ischemia-reperfusion (I-R). Here we have investigated whether FGF-2 cardioprotection: (a) is dependent on flow modulation; (b) is linked to effects on contractility; (c) is mediate...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0832
更新日期:1998-12-01 00:00:00
abstract::Heart rate in mammals is inversely related to body weight. In the etruscan shrew it exceeds 960 beats/min. Since the heart depends primarily on energy from aerobic sources, it was interesting to examine some morphological parameters of the mitochondria in some mammals with a high heart frequency. Volume fraction and s...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(85)80031-6
更新日期:1985-06-01 00:00:00
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
更新日期:2002-05-01 00:00:00
abstract:BACKGROUND:Mitochondrial calcium overload is an important factor in defining ischemia/reperfusion injury. Since pre-menopausal women are relatively protected from ischemia and heart disease, we tested the hypothesis that gender differences alter Ca(2+) handling in rat cardiac mitochondria. METHODS:Using cardiac mitoch...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.04.023
更新日期:2004-08-01 00:00:00
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
更新日期:2015-05-01 00:00:00
abstract::The Na+/Ca2+ exchanger plays an important role in the maintenance of calcium homeostasis in the heart. Therefore, factors which regulate the exchanger have a significant impact on cardiac function. Previously, we showed that the non-hydrolysable GTP analog, 5'guanylyl imidodiphosphate [Gpp(NH)p], stimulates Na+/Ca2+ e...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0002
更新日期:1996-01-01 00:00:00
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
更新日期:2016-12-01 00:00:00
abstract::Our previous studies showed that homocysteine (Hcy) reduces endothelial progenitor cell (EPC) numbers and impairs functional activity. However, the mechanisms by which Hcy reduces EPCs numbers and activity remain to be determined. Recent studies have demonstrated that reduced EPCs numbers and activity was associated w...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.01.011
更新日期:2006-05-01 00:00:00
abstract::The effects of preventing oxidative phosphorylation on pHi were compared in papillary muscles from right ventricles of normal and pressure-overloaded ferret hearts. Hypertrophy was induced by pulmonary artery clipping for 30-45 days. pHi was recorded with pH-sensitive microelectrodes. Resting pHi and the relationship ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(95)90043-8
更新日期:1995-03-01 00:00:00
abstract:BACKGROUND:Hypertrophic cardiomyopathy (HCM) is a prevalent and complex cardiovascular condition. Despite being strongly associated with genetic alterations, wide variation of disease penetrance, expressivity and hallmarks of progression complicate treatment. We aimed to characterize different human isogenic cellular m...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.06.003
更新日期:2020-08-01 00:00:00
abstract::The goal of this study was to test the hypothesis that the novel anti-ischemic drug ranolazine, which is known to inhibit late I(Na), could reduce intracellular [Na(+)](i) and diastolic [Ca(2+)](i) overload and improve diastolic function. Contractile dysfunction in human heart failure (HF) is associated with increased...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.03.006
更新日期:2008-07-01 00:00:00