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)

Complete obstruction of the maternal blood flow to fetal rats at 20 days of gestation for a period of 10 min causes a significant shift of approximately 22% in protein kinase C (PKC) activity from a cytosolic to a membrane-bound form in the fetal brain. This translocation can be entirely reversed without losses in activity by a single intraperitoneal injection into the gravid rat of either a mixture of disialo- and trisialoganglioside [polysialoganglioside (PSG)] or by GM1 (50 mg/kg of body weight) given 3 h before onset of the ischemic episode. Cessation of blood flow for 15 min followed by a reperfusion period of 24 h results in a 47% loss in total PKC activity. This down-regulation can be almost entirely prevented upon intraperitoneal administration of GM1 3 h before, but also during and even 90 min after the onset of ischemia. The PSG mixture is also effective, particularly when given 3 h before the insult. Down-regulation of PKC is accompanied by an increase in a Ca2(+)-phosphatidylserine-independent kinase [protein kinase M (PKM)] activity, which rises from 30 pmol/min/mg of protein in control animals to a maximal value of 83.1 pmol/min/mg of protein after 15 min of ischemia and 6 h of reperfusion. By 24 h, PKM activity is 46.8 pmol/min/mg of protein. Administration of GM1 blocks completely the appearance of PKM, a result suggesting that PKC down-regulation and PKM activity elevation are intimately associated events and that both are regulated by GM1 ganglioside.
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PMID:Gangliosides prevent ischemia-induced down-regulation of protein kinase C in fetal rat brain. 223 Aug 13

A decrease in the rate of protein synthesis as well as an increase in the synthesis time of "medium-size" polypeptide chain were detected in total rabbit myocardium ischemia, which were evaluated using rabbit myocardium cell-free protein-synthesizing systems. The decrease in the synthesis rate of total myocardial proteins was shown to depend on the state of ribosomes function. Redistribution in the pools of membrane-bound and free ribosomes as well as a decrease of polyribosomes amount in total pool of myocardial ribosomes were observed under conditions of total myocardial ischemia.
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PMID:[Various characteristics of protein-synthesizing apparatus of the myocardium during total ischemia]. 223 36

Free radical-mediated reperfusion injury has been established as an important mechanism leading to post-ischemic reperfusion myocardial damage. The present study was undertaken to determine the protective role of vitamin E, a membrane-bound free-radical scavenger, on ischemia-reperfusion myocardial injury. After 4 months of feeding a semipurified diet containing 0, 30, and 3000 ppm of R,R,R,-alpha-tocopherol acetate, rat hearts were subjected to Langendorff perfusion. Myocardial damage was judged by the release of creatine phosphokinase (CPK) after 45 min of global ischemia followed by 20 min of reperfusion. Effluent CPK was significantly lowered in the two tocopherol-supplemented groups, although increasing dietary vitamin E by 100-fold above requirement did not confer further protection. However, effluent prostacyclin, detected as the stable metabolite 6-keto-PGF1 alpha by radioimmunoassay, was potentiated by dietary vitamin E in a dose-dependent manner. Analysis of lipids in cardiac subcellular fractions showed considerable enrichment of tocopherol in these membranes by diets, but the levels of polyunsaturated fatty acids, phospholipids, and cholesterol were essentially unchanged by dietary treatment or ischemia-reperfusion. These data demonstrated that requirement level of tocopherol (30 ppm) in the diet is sufficient to protect against reperfusion injury of the myocardium and suggests that tocopherol is important in maintaining cardiac prostacyclin synthesis under conditions of oxygen stress.
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PMID:Effects of vitamin E on prostacyclin release and lipid composition of the ischemic rat heart. 231 Feb

Unilateral ischemia in the right cerebral hemisphere of the rat was induced by ligation of the right common carotid artery coupled with controlled hemorrhage to produce hypotension (25 +/- 8 mm/Hg). Where indicated after 30 min of ischemia, the withdrawn blood was reinfused to restore arterial pressure to normal. Mitochondria isolated from the ipsilateral hemisphere after 30 min of ischemia showed significantly lower respiratory rates than the organelles isolated from the contralateral side. Oxidation of NAD(+)-linked substrates was more sensitive to inhibition in ischemia (30%) than was of ferrocytochrome c (12%), succinate oxidation being intermediate. The activities of membrane-bound dehydrogenases (both NADH and succinate-linked) were also significantly lowered. Ischemia did not affect the cytochrome content of mitochondria. Respiratory activity (NAD(+)-linked) of mitochondria isolated from the ipsilateral hemisphere was twice as sensitive to inhibition by fatty acid as was of preparations from the contralateral side. Mitochondria isolated from cerebral cortex after 90 min of post-ischemic reperfusion showed no significant improvement in the rate of substrate oxidation. Adenine nucleotide translocase activity and energy-dependent Ca2+ uptake, both of which decreased significantly in mitochondria isolated from the ischemic brain, showed little recovery, on reperfusion. These observations suggested the strong possibility that the deleterious effects of ischemia on mitochondrial respiratory function might be mediated by free fatty acids that are known to accumulate in large amounts in ischemic tissues. The pattern of inhibition of ATPase activity was consistent with this view.
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PMID:Influence of cerebral ischemia and post-ischemic reperfusion on mitochondrial oxidative phosphorylation. 234 84

The fast axonal transport of acetylcholinesterase (AChE) and the slow transport of choline acetyltransferase (ChAT) were measured by the stop-flow ligation technique in the sciatic nerve of rabbits 6 and 24 h after ischemia performed by the occlusion of the abdominal aorta which lasted 40 min. Activities of these enzymes were also measured in punched samples of the spinal cord (L5-6). Results were correlated with those obtained from the sham-operated control group. Six h after ischemia, its only apparent effect was a different distribution of accumulated enzymes in the central nerve segments. Twenty-four h after ischemia, the transport of AChE was markedly depressed; proximodistal accumulation decreased by 68%, whereas enzyme activity in the intact contralateral nerve and in the ventral horns of the spinal cord was preserved. No effect of ischemia on the retrograde axonal transport of AChE was observed in this experimental model. Cytoplasmic ChAT is much more susceptible to necrotic degeneration than membrane-bound AChE; 24 h after ischemia its activity decreased significantly in all investigated parts of the sciatic motoneurones but the rate of slow axonal transport did not seem to be affected.
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PMID:Effect of spinal cord ischemia on axonal transport of cholinergic enzymes in rabbit sciatic nerve. 246 95

A partially purified, membrane-bound Na+-K+-ATPase fraction, prepared from the outer medulla of porcine kidney, was incubated in the presence of 0.1 mM FeCl3, 1 mM ADP, and 0.1-100 mM H2O2 for either 15 or 30 min at 37 degrees C. The activity of ouabain-sensitive Na+-K+-ATPase was reduced proportionally to the concentration of H2O2 and the duration of incubation. There were decreases in SH contents and turnover rates of the Na+-K+-ATPase preparation, while malondialdehyde (MDA) and conjugated dienes were generated from the membrane lipids in the course of the incubation. The concentrations of ethanolamine (E) plasmalogen and of arachidonic acid in the E glycerophospholipid molecules were reduced by the free radical reaction. Similarly, a reduction in Na+-K+-ATPase activity and the formation of MDA and conjugated dienes, together with a decrease in E glycerophospholipids, were observed when the membrane fraction was exposed to ultraviolet irradiation (254 nm) for 30 min at 4 degrees C. Administration of 10 mM dithiothreitol alleviated the reductions in enzyme activity, in turnover rate, and in SH content without suppressing MDA formation. Addition of 2 mM butylated hydroxytoluene to the incubation mixture prevented the lipid peroxidation without totally normalizing the enzyme activity in the H2O2 experiment, whereas this antioxidant restored the ATPase activity to normal in the ultraviolet experiment. Microsomal fractions, prepared from the outer medulla of canine kidney after 1 h of unilateral ischemia and 1 h of reperfusion, showed a decreased Na+-K+-ATPase activity, a reduced amount of SH groups, and an increased MDA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Depression of membrane-bound Na+-K+-ATPase activity induced by free radicals and by ischemia of kidney. 283 28

We investigated the hypothesis that ouabain would reduce energy expenditure in the hypothermic, ischemic heart by inhibiting membrane-bound sodium/potassium-activated adenosine triphosphatase and lead to improved function on reperfusion. Additionally, we compared ouabain with another potential adjunct, the calcium channel blocker verapamil. The isolated rabbit heart was used as a model, and three experimental groups were studied after 1, 6, 12, and 24 hours of 4 degrees C ischemia. Hearts in group I were stored in a standard high potassium solution; hearts in groups II and III were stored in the same solution supplemented with verapamil (2 mg/L) and ouabain (3 mg/L), respectively. After ischemia, all hearts were reperfused for 45 minutes on a modified Langendorff apparatus, and left ventricular function was measured before freeze-clamping the heart for metabolite determination. At 1 and 6 hours, hearts in all groups functioned well, but the group III hearts had higher levels of adenosine triphosphate, phosphocreatine, total adenine nucleotides, and glycogen. After 12 hours of ischemia, function was significantly better in group III hearts (p less than 0.01) compared with that of hearts in groups I and II. Group III hearts also exhibited higher levels of high energy phosphates and glycogen. After 24 hours of storage, all hearts functioned poorly, and there was a marked decline in measured metabolites. Although we could show no improvement with the addition of verapamil, ventricular function was improved after storage in a high potassium hypothermic solution containing ouabain. Because ouabain inhibits the hydrolysis of adenosine triphosphate by sodium/potassium-activated adenosine triphosphatase, this result suggests that the glycoside maintains energy-rich phosphates necessary for optimal resumption of cardiac function.
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PMID:Improved recovery of cardiac function after hypothermic ischemic storage with ouabain. 284 69

A large amount of biochemical, physiological, and pharmacological data has been obtained which supports a mechanistic role of oxygen free radical-induced lipid peroxidation (LP) in post-traumatic spinal cord degeneration. Biochemical evidence of early and progressive lipid peroxidative reactions occurring in the injured spinal cord includes: an increase in polyunsaturated fatty acid peroxidation products (e.g., malonyldialdehyde), a decrease in cholesterol and the appearance of cholesterol oxidation products, an increase in cyclic GMP presumably due to free radical activation of guanylate cyclase, a decrease in tissue anti-oxidant levels (e.g., alpha tocopherol, reduced ascorbate), and inhibition of membrane-bound enzymes such as Na+ + K+-ATPase. In vitro CNS tissue studies have provided support for the possibility that LP may contribute to other early post-traumatic events including intracellular calcium accumulation and arachidonic acid release. Moreover, spinal tissue lactic acidosis, which occurs early after injury, can exacerbate LP reactions. The involvement of LP in the development of progressive post-traumatic spinal white matter ischemia has been strongly inferred from pharmacological studies in cats with known inhibitors of LP. For example, the dose-response curves for the ability of the glucocorticoid methylprednisolone (MP) to inhibit post-traumatic LP and to retard ischemia development are identical. This relationship between LP and post-traumatic ischemia is more directly implied from studies showing that pretreatment of cats with high doses of anti-oxidants (e.g., d-alpha tocopherol plus selenium p.o. or 1-ascorbic acid i.v.) can also significantly antagonize the progressive decrease in spinal cord blood flow that follows severe blunt injury. However, a similar efficacy of certain calcium and prostaglandin antagonists suggests an interrelationship between aberrant calcium fluxes, vasoconstrictor/platelet aggregating prostanoids, and LP in the post-traumatic ischemic phenomenon. In addition to a role of LP in ischemia development, the action of intensive d-alpha tocopherol and selenium pretreatment to retard anterograde cat motor nerve fiber degeneration after nerve section suggests that LP may also be a fundamental mechanism of "Wallerian" axonal degeneration after neural injury. Finally, a critical role of LP in the acute pathophysiology of CNS injury in general has been supported by the finding of an excellent correlation, in terms of efficacy and potency, between the action of glucocorticoid and nonglucocorticoid steroids to inhibit neural tissue LP in vitro and to promote early neurological recovery in severely head-injured mice.
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PMID:Role of lipid peroxidation in post-traumatic spinal cord degeneration: a review. 355 50

It was shown in experiments in vitro that thermal ischemia of liver tissue leads to disorders in the function of membrane-bound microsomal monooxygenases. Disorders in the structural organization of membranes were also expressed in the inhibition of reactions of ascorbate-depending and fermentative peroxide oxidation of lipids and labilization of lysosomal membranes. Faults in the rate of amidopyrine n-demethylation and aniline n-hydroxylation correlate with the intensification of spontaneous peroxidation of lipids and activation of proteolytic processes in ischemia. The obtained data permitted to ground the approach to pharmacological prophylaxis of ischemic damages of liver microsomal monooxygenases.
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PMID:[Mechanisms of the damage to the liver monooxygenase systems in thermal ischemia]. 370 79

Studies in the globally ischemic, isolated rat heart have shown that the preischemic coronary infusion of calcium-free cardioplegic solution may lead to an exacerbation of the postischemic leakage of creatine kinase. This exacerbation could be prevented by the inclusion of trace amounts of calcium in the coronary infusate or could be postponed by the omission of calcium during postischemic reperfusion. The calcium paradox, observed with such a combination of coronary infusion and ischemia required for its induction a less extensive cellular calcium depletion than that induced by infusion only and was the result of 2 additive factors: the washout of tissue calcium during preischemic infusion and the cellular influx of residual membrane-bound calcium during ischemia. The balance between protective and damaging properties with calcium-free cardioplegic infusates was influenced by the concentration of Na+, K+, Mg++ and procaine in the infusates as these agents influence patterns of calcium redistribution.
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PMID:Protection of the ischemic myocardium calcium-free cardioplegic infusates and the additive effects of coronary infusion and ischemia in the induction of the calcium paradox. 616 28


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