Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protein kinase activity in cytosol was similar in control, ischemic, and reperfused hearts; however, a 1.5-fold increase in membrane protein kinase activity was induced by ischemia and reperfusion. The H-7 inhibitable cytosolic protein kinase activity decreased by 40% with 30 min ischemia, while that of membrane fraction increased 1.8-fold. However, the CGS9343B inhibitable protein kinase activity in cytosolic fractions was unaffected by ischemia, while that of membrane increased by about 1.7-fold. These results suggest that myocardial ischemia is associated with enhanced protein kinase C and calmodulin-dependent kinase activities in membrane fraction. Furthermore, the results also suggest a translocation of protein kinase C activity from the cytosol to the membrane. Reperfusion of ischemic myocardium did not result in any further increase of protein kinase C and calmodulin-dependent kinase activities in the membrane. These enhanced protein kinase activities also resulted in an enhanced phosphorylation of endogenous membrane proteins. The creatine kinase released from the heart was increased by both ischemia and reperfusion. Therefore, these results suggest that biochemical cascades of reactions caused by enhanced membrane protein kinase C and calmodulin-dependent kinase activities may contribute to ischemic-reperfusion injury.
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PMID:Enhanced membrane protein kinase C activity in myocardial ischemia. 131 57

To investigate whether slow Ca2+ channel blockers protect against development of changes in properties of the sarcolemma and in the tissue ultrastructure during myocardial ischemia, nifedipine was administered prior to occlusion (up to 3 hours) of the left anterior descending coronary artery in anesthetized pigs. Intravenous doses which reduced arterial blood pressure by 20-25%, had no effect on the time-dependent reduction of Ca2+-calmodulin and cyclic AMP-dependent 32P incorporation into sarcolemmal phospholamban-like protein. Nifedipine blocked the reduction in the activity of sarcolemmal 5'-nucleotidase. Nifedipine had no significant effect on the long-chain fatty acylcarnitine accumulation in sarcolemma. A marked delay in the appearance of ultrastructural indicators of irreversible tissue injury in subepicardial myocardium was observed, when nifedipine was infused. Particularly the reduced appearance of electron-dense bodies in mitochondria suggested a reducing effect of nifedipine on cellular net gain of Ca2+. Apparently, ischemia-induced loss of the ability of the proteinkinases to incorporate phosphate into sarcolemmal phospholamban-like protein is not a process secondary to Ca2+ overload of the myocardium. The involvement of accumulation of long-chain fatty acylcarnitine within the sarcolemma may also be excluded. The membrane defect as indicated by a change in phosphorylation-mediated control of Ca2+ transport may itself be associated with the development of ischemia (-reperfusion)-induced Ca2+ overload.
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PMID:The effect of nifedipine on ischemia-induced changes in the biochemical properties of isolated sarcolemmal vesicles and the ultrastructure of myocardium. 303 May 20

Calmodulin (CaM) is the primary Ca2+ regulatory protein in cardiac cells, thus alterations in calmodulin would greatly influence the contractile response and may play a role in the abnormal calcium handling observed in human heart failure. We used Northern blot analysis to determine changes in calmodulin mRNA expression in left ventricular tissues isolated from 20 failing and four control human hearts. Only hearts with failure due to idiopathic dilated cardiomyopathy (DCM) or ischaemic heart disease (IHD) were studied. A human calmodulin cDNA probe 95% homologous to Type 3 CaM was used, which hybridized to a single 2.3 kb mRNA. CaM mRNA levels were expressed as a function of total RNA, as determined by hybridization to an 18S cDNA probe, and as a function of myocyte specific mRNA, as determined by hybridization to a myosin heavy chain (MHC) cDNA probe. In both DCM and IHD, CaM mRNA expression relative to total RNA (CaM/18S), was significantly decreased (45% and 61%, respectively) compared to control hearts. CaM mRNA expression in DCM tissues was also significantly decreased (45%) relative to myocyte specific mRNA (CaM/MHC), when compared to control hearts. In IHD, CaM mRNA was not significantly decreased in relation to myocyte specific mRNA, which suggests a greater loss of myocytes or contractile proteins in IHD as compared with DCM. The decreased expressed of CaM mRNA observed in failing hearts could affect many Ca(2+)-dependent processes, and contribute to the inability of these hearts to handle Ca2+ in a viable manner.
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PMID:Decreased expression of calmodulin mRNA in human end-stage heart failure. 819 73

We investigated the effects of nifedipine on cyclic GMP turnover and the pertinent enzyme activities in cultured coronary smooth muscle cells (SMC). Nifedipine at high concentrations slightly decreased basal soluble guanylate cyclase activity and inhibited the action of sodium nitroprusside (SNP) but had no effect on the particulate form of the enzyme. In contrast, nifedipine inhibited cyclic GMP hydrolysis by directly inhibiting the partially purified calmodulin-stimulated isoform of phosphodiesterase (type I PDE) with IC50 of 4.2 microM. Nifedipine > or = 1.0 microM enhanced cyclic GMP accumulation in response to 1.0 microM SNP, although nifedipine alone exerted no influence on cyclic GMP levels. Enhancement of cyclic GMP accumulation by nifedipine in response to SNP was not affected by BAY K 8644, a calcium channel agonist. These properties may be shared by other dihydropyridines since nicardipine and nisoldipine also inhibited type I PDE with similar IC50. However, some other structurally unrelated calcium channel blockers, diltiazem and verapamil, had little effect on cyclic nucleotide hydrolysis or on cyclic GMP accumulation in response to SNP. Nifedipine may synergistically enhance cyclic GMP accumulation in response to nitric oxide (NO)-releasing agents by directly inhibiting type I PDE in coronary SMC. Such effects of nifedipine may partly contribute to coronary vasodilation and prevention of coronary spasm in patients with ischemic heart disease.
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PMID:Effect of nifedipine on cyclic GMP turnover in cultured coronary smooth muscle cells. 856 20

Intracellular calcium (Cai2+) and left ventricular (LV) function were determined in the coronary-perfused mouse heart to study Cai2+-related mechanisms of injury from myocardial ischemia and reperfusion. Specifics for loading of the photoprotein aequorin into isovolumically contracting mouse hearts under constant-flow conditions are provided. The method allows detection of changes in Cai2+ on a beat-to-beat basis in a model of myocardial stunning and permits correlation of interventions that regulate Ca2+ exchange with functional alterations. Twenty-three coronary-perfused mouse hearts were subjected to 15 min of ischemia followed by 20 min of reperfusion. In 13 hearts, the perfusate included the calmodulin antagonist W7 (10 microM) to inhibit Ca(2+)-calmodulin-regulated mechanisms. Peak Cai2+ was 0.77 +/- 0.03 microM in the control group and was unaffected by W7 at baseline. Ischemia was characterized by a rapid decline in LV function, followed by ischemic contracture, accompanied by a gradual rise in Cai2+. Reperfusion was characterized by an initial burst of Cai2+ and a gradual recovery to nearly normal systolic Cai2+ while LV pressure recovered to 55% after 20 min of reperfusion (stunned myocardium). These results in the mouse heart confirm that stunning does not result from deficiency of Cai2+ but rather from a decreased myofilament responsiveness to Cai2+ due to changes in the myofilaments themselves. In hearts perfused with W7, the rise in Cai2+ during ischemia was significantly attenuated, as was the magnitude of mean Cai2+ during early reflow. Ischemic contracture was abolished or delayed. Hearts perfused with W7 showed significantly improved recovery of LV pressure, rate of contraction, and rate of relaxation. Diastolic Cai2+ was increased in control hearts during stunning but returned to baseline in hearts perfused with W7. Simultaneous assessment of Cai2+ and LV function demonstrates that calmodulin-regulated mechanisms may contribute to the pathogenesis of myocardial stunning in the mouse heart.
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PMID:Intracellular calcium dynamics in mouse model of myocardial stunning. 961 95

Because the net Ca2+ uptake in the sarcoplasmic reticulum (SR) of cardiac muscle is a result of the activity of Ca(2+)-ATPase and of the SR Ca(2+)-release channel, an abnormal Ca2+ uptake may be the result of the dysfunction of either or both structures. The site or sites of action for oxygen-derived free radicals (OFR) damage are unknown, although previous studies on the SR have focused on damage to the Ca2+ pump. Direct effects of OFR on SR Ca(2+)-release channels may be important in understanding their potential contribution to myocardial ischemia/reperfusion injury. We confirmed that superoxide anion radical (O2.-) generated from hypoxanthine-xanthine oxidase reaction decreases calmodulin content and increases 45Ca2+ efflux from the heavy fraction of canine cardiac SR vesicles. Electron spin resonance study showed that hydroxyl radicals are generated in addition to O2.- from hypoxanthine-xanthine oxidase reaction, and data indicate that O2.- is responsible for the observed effect. Current fluctuations through single Ca(2+)-release channels have been also monitored after incorporation into planar phospholipid bilayers. We directly demonstrate that activation of the channel by O2.- stimulates Ca2+ release from heavy SR vesicles and suggest the importance of accessory proteins such as calmodulin in modulating the effect of O2.-.
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PMID:[Superoxide anion radical selectively increases Ca2+ release from cardiac sarcoplasmic reticulum through ryanodine receptor Ca2+ channel]. 1019 Jan 35

Although beta-adrenoceptor (beta-AR) blockers are used for the treatment of ischemic heart disease, the mechanisms of their beneficial actions have not been fully elucidated. In view of the role of sarcoplasmic reticular (SR) abnormalities in cardiac dysfunction due to ischemia-reperfusion (I/R), we examined the effects of beta-AR blockers on the I/R-induced changes in SR Ca(2+) uptake and release, as well as the protein contents and gene expression of ryanodine receptor, SR Ca(2+)-pump, phospholamban, and calsequestrin. I/R in isolated rat hearts was induced by stopping the perfusion for 30 min and then reperfusing the ischemic hearts for 60 min. Hearts were treated with or without 10 microM atenolol, a beta(1)-specific blocker, or 10 microM propranolol, a nonspecific beta-blocker, 10 min before inducing ischemia as well as during the reperfusion period. I/R depressed cardiac performance, SR Ca(2+) uptake, and Ca(2+) release activities, protein contents, as well as Ca(2+)/calmodulin-dependent protein kinase and cAMP-dependent protein kinase-mediated phosphorylations, significantly. The mRNA levels for SR Ca(2+) pump, ryanodine receptors, phospholamban, and calsequestrin were also reduced by I/R. All these changes due to I/R were partially prevented by beta-AR blocker treatment. The results indicate that the beneficial effects of beta-AR blockers on cardiac performance in the I/R hearts may be related to the prevention of changes in SR Ca(2+) uptake and release activities, protein contents, as well as Ca(2+)/calmodulin-dependent protein kinase and cAMP-dependent protein kinase phosphorylations of SR proteins. On the other hand, the protection of I/R-induced alterations in mRNA levels for SR proteins by beta-AR blockers suggests cardiac SR gene expression as a molecular site of their cardioprotective action.
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PMID:Effect of beta-adrenoceptor blockers on sarcoplasmic reticular function and gene expression in the ischemic-reperfused heart. 1073 48

In this review we analyse the experimental and clinical findings demonstrating important regulatory significance of met-enkephalin, leu-enkephalin and their derivatives in the control of cardiovascular system activity. Enkephalin-positive immunoreactivity is revealed in the heart of different species of animals, and their cardiovascular effects are established in numerous investigations. It is determined that cardiac effects of enkephalins are essentially associated with modulatory influence at the presynaptic and postsynaptic levels on the activity of extracardiac neural regulation. Cardiovascular effects of endogenous opioid system are extremely important in developing of myocardial ischemia, cardiac arrhythmias and congestive heart failure. The cellular mechanisms of opioid effects are associated with stimulation of mu- and delta-subtypes of opiate receptors which stimulation of mu- and delta-subtypes of opiate receptors which are coupled with conductivity of ion channels, adenylate cyclase activity, phosphoinositide turnover and calcium-calmodulin-dependent protein kynases.
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PMID:[The regulatory effects of opioid peptides--enkephalins--in controlling the activities of the cardiovascular system]. 1075 29

Ca(2+)/calmodulin-dependent protein kinase (CaMK) family is responsive to changes in the intracellular Ca(2+) concentration. However, their functions have not been well established in the ischemia/reperfusion heart. The effects of myocardial ischemia on CaMKII, the most strongly expressed form, were investigated using isolated rat hearts. Rat hearts were rendered globally ischemic by stopping perfusion for 15 min, and then reperfused, heart ventricles being analyzed in each phase. Western blotting detected a decrease in the cytosolic and concomitant increase in the particulate fraction of CaMKII following transient ischemia. Redistribution to the cytosol was revealed on reperfusion. Northern blot showed CaMKII gene expression decreased by ischemia. Furthermore, autoradiography and confocal immunohistochemical findings provided autophosphorylation of CaMKII in the cytosol, ischemia causing decrease, with gradual recovery on reperfusion. These results indicate a transient partial translocation of CaMKII accompanied by kinase activity, with residual myocardial CaMKII undergoing autophosphorylation during ischemia and reperfusion, demonstrating two different characteristic dynamics of CaMKII.
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PMID:Dynamics of Ca(2+)/calmodulin-dependent protein kinase II following acute myocardial ischemia-translocation and autophosphorylation. 1235 53

The catalytic activity of calcium-independent phospholipase A2 (iPLA2), which is classified as a group VI PLA2, is regulated by protein kinase C, calmodulin, and others such as reactive oxygen species. Numerous findings have shown that iPLA2 is involved in stimulus-induced arachidonic acid release and lysophospholipid generation, although the participation is dependent upon the cell type and stimulus. The catalytic action of iPLA2 is known to be responsible for phospholipid remodeling as a housekeeping function. However, it has been widely accepted that arachidonic acid and lysophospholipid generated by iPLA2 act as a signaling molecule in cellular functions. Those include eicosanoid production, glucose-induced insulin secretion, Fas-induced apoptosis, cellular proliferation, membrane traffic in fusion, contribution to myocardial ischemia, and others. In this review, the functional role of iPLA2 in cellular responses upon stimulation is the focus.
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PMID:Cellular function of calcium-independent phospholipase A2. 1530 16


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