Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the role of Ca-calmodulin complex in the development of myocardial injury caused by ischemia and reperfusion, an isolated working rat hearts were subjected to ischemia/reperfusion with and without calmodulin antagonist, trifluoperazine (TFP 5 x 10(-7)M) in the perfusion medium. In TFP-treated hearts postischemic recovery of hemodynamic function was markedly improved and the release of LDH and malondialdehyde (MDA) significantly reduced as compared with control hearts. It is concluded that: 1) calmodulin-dependent mechanism seems to be involved in peroxidative injury of cellular membranes, 2) cardioprotective effect of TFP results at least in part from prevention of membrane damage caused by lipid peroxidation.
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PMID:Calmodulin antagonist reduces release of malondialdehyde from isolated ischemic/reperfused rat heart. 325 57

Models of ischemic and reperfusion arrhythmias were reproduced in isolated rat hearts by means of the ligation and subsequent reocclusion of the left descending coronary artery. The introduction of trifluoperazine (TFP, 10(-6) M) and verapamil (2.5 X 10(-8) M) into the perfusion medium produced a 20% depression of contractility in aerobic conditions; an additional depression of contractility at 20 min of ischemia and 10 min of reperfusion was 40 and 50%, respectively, for TFP and about the same for verapamil, as compared to the control. Antiarrhythmic effect of TFP was much higher, as compared to that of verapamil. The calmodulin blocker reduced fivefold total duration of arrhythmias, whereas the calcium-incorporation blocker only reduced it by 2.5 times. The antiarrhythmic effect of TFP was even more marked, as compared to verapamil, at reperfusion: TFP reduced total duration of ventricular tachycardias and ventricular fibrillations by 2 and 35 times, respectively, while verapamil had no effect on those types of arrhythmia. A possible mechanism of antiarrhythmic action of the calmodulin blocker TFP is discussed.
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PMID:[Prevention of ischemic and reperfusion arrhythmias using the calmodulin blocker trifluoperazine]. 341 68

It is shown in experiments on rats that the early postischemic period after 1- and 1.5-hour ischemia of kidneys is characterized by a decrease in the damage of the glycolytic system site which induces glucose-6-phosphate transformation into lactate and by an increase in the inhibition intensity of the initial hexokinase reaction of glycolysis. In the postischemic period after more prolonged (2-, 3-hour) ischemia the damage of the glycolytic system develops also at the site of glucose-6-phosphate transformation into lactate. Administration either of the nucleotide complex (NAD and AMP) or calmodulin inhibitors (aminazine and zinc sulphate) to rats prior to two-hour occlusion of kidneys vessels promotes a decrease in the inhibition of the glycolytic system activity in the postischemic period. At the same time the separate and combined application of zinc sulphate and triftazin (the most intensive calmodulin inhibitor) is not efficient. The positive effect of NAD, AMP and aminazine on the state of the glycolytic kidney system in the postischemic period correlates with the improvement of the blood microcirculation processes in them.
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PMID:[Glycolysis in the rat kidney shortly after ischemia and administration of calmodulin inhibitors, AMP and NAD]. 379 79

The levels of two calcium-binding proteins, S-100 protein and calmodulin, were measured serially in the cerebrospinal fluid (CSF) of patients after subarachnoid hemorrhage (SAH) and aneurysm surgery. These two proteins have a similar molecular structure and are highly concentrated in the central nervous system (CNS). The levels of S-100 protein found in the earliest postoperative CSF samples correlated with the preoperative SAH grades. High S-100 protein levels in the CSF were found in patients with poor SAH grades. Moreover, the prognosis of the patients correlated with the S-100 protein levels in the CSF samples taken during the immediate postoperative period and with the daily changes of the S-100 protein levels. Severe diffuse cerebral vasospasm was followed by a sharp S-100 protein increase. These results suggest that S-100 protein levels in the CSF provide a useful index of organic damage in the CNS, and furthermore that S-100 protein levels and their changes may have prognostic value for patients after SAH. On the other hand, there was a lack of correlation between the calmodulin levels and the preoperative grade or outcome. It would be inappropriate, however, to speculate from the results of this study that these calcium-binding proteins in the CSF play any causative role in pathological processes such as cerebral vasospasm or brain ischemia after SAH, since changes in the levels of these proteins followed the onset of clinical signs of deterioration.
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PMID:S-100 protein and calmodulin levels in cerebrospinal fluid after subarachnoid hemorrhage. 402 Apr 69

Experiments were designed to evaluate whether cardiac ischemia affected the subcellular distribution of calmodulin activity. Major cellular fractions (nuclei, mitochondria, sarcoplasmic reticulum and cytosol) were isolated from globally ischemic hearts by differential centrifugation. Ischemia did not affect calmodulin activity in cell fractions other than sarcoplasmic reticulum, which showed a consistent and complete loss of activity. This site-specific loss of calmodulin activity may be one mechanism by which ischemia induces contractile dysfunction.
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PMID:Loss of calmodulin activity in cardiac sarcoplasmic reticulum after ischemia. 402 51

The superoxide radical plays major roles in the neutrophil-medicated acute inflammatory response and in postischemic tissue injury, although the sources and actions of the radical are quite different in these two pathological states. While neutrophils produce superoxide for the primary purpose of aiding in the killing of ingested microbes, a second useful function has evolved. The superoxide released from actively phagocytosing neutrophils serves to attract more neutrophils by reacting with, and activating, a latent chemotactic factor present in plasma. Superoxide dismutase, by preventing the activation of this superoxide-dependent chemotactic factor, exerts potent anti-inflammatory action. During ischemia, energy-starved tissues catabolize ATP to hypoxanthine. Calcium transients in these cells appear to activate a calmodulin regulated protease which attacks the enzyme xanthine dehydrogenase, converting it to a xanthine oxidase capable of superoxide generation. When the tissue is reperfused and reoxygenated, all the necessary components are present (xanthine oxidase, hypoxanthine, and oxygen) to produce a burst of superoxide which results in extensive tissue damage. Ischemic tissues are protected by superoxide dismutase or allupurinol, an inhibitor of xanthine oxidase.
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PMID:The pathophysiology of superoxide: roles in inflammation and ischemia. 629 73

Adenylate cyclase activity was investigated in either homogenate or particulate fractions from the frontal cerebral cortex of the gerbil following five experimental conditions of bilateral ischemia. After periods of 15 min ischemia, 15 min ischemia plus 15 min of recirculation or 60 min ischemia the enzyme generally displayed enhanced responses to GTP, norepinephrine (NE), dopamine (DA), NE + GTP and DA + GTP. Pretreatment of the gerbils with methylprednisolone, allopurinol or indomethacin did not significantly influence the outcome of these findings. When the animals were subjected to 60 min ischemia plus 15 min of reflow, enzyme responses to the stimulatory agents including forskolin and NaF were all reduced. Pretreatment with methylprednisolone, allopurinol or indomethacin prevented the damage to adenylate cyclase in the 60 min ischemia plus 15 min reflow animals. When animals were made ischemic for 15 min followed by one week of recovery, enzyme sensitivity to GTP, calmodulin-Ca++, NE, combinations thereof and forskolin were reduced in only the particulate fractions. Enzyme damage was reversed following methylprednisolone. Enzyme damage may result from generation of free radicals during reflow and drugs that either inhibit synthesis pathways generating free radicals, stabilize cell membranes or act as free radical scavengers may be therapeutically beneficial under specific conditions of stroke.
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PMID:Protective action by methylprednisolone, allopurinol and indomethacin against stroke-induced damage to adenylate cyclase in gerbil cerebral cortex. 670 40

This study analyzed the ability of the N-methyl-D-aspartate receptor antagonist dextrorphan (DX) to prevent neuronal degeneration (analyzed by light microscopy), calmodulin (CaM) redistribution (analyzed by immunocytochemistry) and changes in activity of two major Ca(2+)-dependent protein kinases--calcium/calmodulin-dependent protein kinase II (CaM-KII) and protein kinase C (PKC) (analyzed by specific substrate phosphorylation) after 20 min of global ischemia (four-vessel occlusion model) in rats. DX treatment before and after ischemia significantly protected hippocampal and cortical neurons from neurodegeneration whereas DX posttreatment alone did not have any effect on preservation of neuronal morphology as compared with placebo treatment analyzed 72 h after 20 min of ischemia. Similarly to histological changes, DX exhibited protection against redistribution of CaM observed after ischemia. These changes were detected both in hippocampus as well as in cerebral cortex. Finally, DX administered before ligation of the carotid arteries reduced loss in both CaM-KII and PKC activity evoked by ischemia.
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PMID:Neuronal protection and preservation of calcium/calmodulin-dependent protein kinase II and protein kinase C activity by dextrorphan treatment in global ischemia. 768 73

Collateral blood vessels supplement normal coronary blood flow and coronary blood flow compromised by coronary artery disease, thereby protecting the myocardium from ischemia. Collateral vessel formation is the result of angiogenesis. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is a secreted mitogen specific for endothelial cells and an extremely potent angiogenic factor. In the present study, VPF/VEGF mRNA and protein were demonstrated to be markedly stimulated in primary rat cardiac myocytes in vitro in response to reduction of the oxygen tension to 1% or inhibition of the electron transport chain. Four isoforms of VPF/VEGF were coordinately regulated by hypoxia, including a novel isoform not previously described. Phorbol ester and the depolarizing agent veratridine, stimulators of protein kinase C and calcium influx, respectively, were found to markedly increase VPF/VEGF mRNA expression in cardiac myocytes. Forskolin, a potent stimulator of adenylate cyclase, produced a small but significant increase in VPF/VEGF mRNA expression in the cardiac myocytes. However, only H7, an inhibitor of protein kinase C, inhibited the hypoxic induction of VPF/VEGF mRNA; inhibitors of calcium influx and the calcium-calmodulin-dependent protein kinase II as well as inhibition of protein kinase A did not block the hypoxic induction of VPF/VEGF mRNA. This suggests that more than one signal transduction pathway is involved in regulating VPF/VEGF expression. The sensor that regulates the expression of hypoxia-responsive genes has been proposed to be a heme protein. Consistent with this model, transition metals initiate a genetic program similar to hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of vascular endothelial growth factor in cardiac myocytes. 772 92

The influence of brain ischemia on the subcellular distribution and activity of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) was studied in various cortical rat brain regions during and after cerebral ischemia. Total CaM kinase II immunoreactivity (IR) and calmodulin binding in the crude synaptosomal fraction of all regions studied increase but decrease in the microsomal and cytosolic fractions, indicative of a translocation of CaM kinase II to synaptosomes. The translocation of CaM kinase II to synaptic junctions occurs but not to synaptic vesicles. The translocation in neocortex and CA3/DG (dentate gyrus) is transient, whereas in the hippocampal CA1 region, it persists for at least 1 day of reperfusion. The Ca2+/calmodulin-dependent activity of CaM kinase II in the subsynaptosomal fractions of neocortex is persistently decreased by up to 85%, despite the increase in CaM kinase II IR. The decrease in activity is more pronounced than the decline in IR, suggesting that CaM kinase II is covalently modified in the postischemic phase. The persistent translocation of CaM kinase II in the vulnerable ischemic CA1 region indicates that a pathological process is sustained in the area after the reperfusion phase and this may be of significance for ischemic brain injury.
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PMID:Persistent translocation of Ca2+/calmodulin-dependent protein kinase II to synaptic junctions in the vulnerable hippocampal CA1 region following transient ischemia. 779 23


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