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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors investigated the high affinity binding of [3H] muscimol to the receptor of synaptic plasma membranes (SPM) isolated from a normoxic and ischemic brain. Brain ischemia enhanced the [3H] muscimol binding to the receptor, located in native (Triton X-100 untreated) membranes. Scatchard's analysis showed that the total number of binding sites (BMAX) and the KD value increased by about 60%. The higher KD value persisted during 20 min of the reperfusion period. Concomitantly, ischemia stimulated the activity of phospholipase C and phospholipase A2, acting against phosphatidylinositol (PI). The degradation of PI and a transient accumulation of docosahexaenoic and arachidonic acids may be important factors involved in the modification of high affinity agonist binding to the GABAA receptor of SPM isolated from the brain submitted to ischemia.
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PMID:Brain ischemia increased high affinity binding of [3H]muscimol into synaptic plasma membrane receptor. 196 57

We investigated the role of phospholipase A2 (PLA2) and phospholipase C (PLC) in myocardial phosholipid degradation and cellular injury during reperfusion of ischemic myocardium. For this purpose, isolated rat hearts were perfused with isotopic arachidonic acid to label its membrane phospholipids. Hearts preperfused with antiphospholipase A2 (anti-PLA2) retained a significantly higher amount of radiolabel in phosphatidylcholine and phosphatidylinositol and a corresponding lower amount of radiolabel in lysophosphatidylcholine and nonesterified fatty acids (P less than 0.05) after 30 min of reperfusion following 30 min of normothermic global ischemia compared with hearts preperfused with nonimmune immunoglobulin G. In similar experiments, antiphospholipase C (anti-PLC)-treated hearts were associated with significantly (P less than 0.05) higher radiolabel in all phospholipids and lower radiolabel in diacyglycerol compared with nonimmune immunoglobulin G-treated hearts. Measurement of phospholipase activity in subcellular organelles of these hearts showed decreased PLA2 activity in cytosol, mitochondria, and microsomes of anti-PLA2-treated hearts and decreased PLC activity of microsomes in anti-PLC-treated hearts. Furthermore, both the antiphospholipases attenuated the release of creatine kinase and lactate dehydrogenase into perfusate and increased contractility as well as coronary flow in the reperfused hearts. Results of this study suggest that both PLA2 and PLC are involved in the degradation of phospholipids and cellular injury that occur during reperfusion of ischemic myocardium.
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PMID:Role of phospholipases A2 and C in myocardial ischemic reperfusion injury. 200 Sep 82

The activity of phospholipase C acting against [3H]-inositol-phosphatidylinositol (PI) and the activity of arachidonic acid (AA) release from [1-14C]arachidonoyl-phosphatidylinositol by enzyme(s) located in synaptic vesicles (SV) isolated from normoxic and ischemic brains was investigated. Brain ischemia significantly activated phospholipase C (PhLC) by about 90% and AA release by about 50%. PhLC and AA release in SV isolated from brain submitted to ischemia were not further activated by 2 mM CaCl2 contrary to the enzymes from normoxic brain. The activation of PhLC and PhLA2 may produce conformational changes and rearrangement of the SV membranes leading to vesicle-membrane fusion and subsequently to massive neurotransmitter release known to occur during ischemia.
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PMID:Synaptic vesicle-bound phospholipase(s) acting on phosphatidylinositol exhibit(s) high susceptibility to brain ischemia. 211 86

It is well known that levels of free fatty acids (FFA) in the brain rapidly increase during ischemia. FFA release during ischemia is generally due to the disturbance of reacylation by ATP depletion and deacylation from membrane phospholipids by the action of phospholipase. The present study examined the regional difference in brain FFA levels and also the action of phospholipase from the effect of NMDA antagonist (MK-801) and phospholipase C inhibitor (PMSF) on FFA release during complete ischemia in rat brain. Complete brain ischemia was induced with cardiac arrest by intracardiac injection of KCI. A focused microwave was irradiated to the head of rats 0, 2, 4 and 8 minutes after cardiac arrest. Samples of the neocortex, striatum, hippocampus and thalamus were dissected. FFA were measured in each sample. In the vulnerable regions such as neocortex, hippocampus and striatum, arachidonic acid and other FFA levels rapidly increased from the onset of ischemia. All FFA levels in the thalamus were significantly lower than those in the other regions during ischemia. The regional difference of FFA levels during ischemia seemed to be responsible for the regional difference of the vulnerability to ischemia. MK-801 inhibited the FFA release mainly from phosphatidylcholine and phosphatidylethanolamine between 2 and 4 minutes of ischemia. On the other hand, PMSF inhibited the FFA release mainly from phosphatidylinositol during the first 2 minutes of ischemia and from phosphatidylcholine and phosphatidylethanolamine until 8 minutes of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Regional difference in free fatty acids release and the action of phospholipase during ischemia in rat brain]. 228 77

The effect of 10 min ischemia on the activity of phospholipase C acting against [3H]inositol-phosphatidylinositol (PI) and [3H]inositol-phosphatidylinositol 4,5-bisphosphate (PIP2) in the brain subsynaptosomal fractions was investigated. In the presence of endogenous CaCl2, specific activity of phospholipase C acting on phosphatidylinositol was as follows: synaptic cytosol (SC) greater than synaptic vesicles (SV) greater than synaptic plasma membrane SPM). Brain ischemia activated phospholipase C acting on PI by about 60% and 40% in SV and SPM, respectively. The enzyme of synaptic cytosol was not affected by ischemic insult. Phospholipase C acting against PIP2 in the presence of endogenous calcium expressed the specific activity in the following order: SV greater than SPM greater than SC. After 10 min of brain ischemia, activity of phospholipase C acting on PIP2 was significantly suppressed in all subsynaptosomal fractions by about 50-60%. These results indicate that prolonged ischemia produced activation exclusively of phospholipase C acting against phosphatidylinositol.
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PMID:Prolonged ischemia differently affects phospholipase C acting against phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate in brain subsynaptosomal fraction. 255 83

Ischemic rat brains were prepared by decapitation followed by incubation in an artificial cerebrospinal fluid at various times at 37 degrees C, and the levels of phospholipids, free fatty acids, and enzymes involved in their metabolism were studied. Activities of phospholipase A, phospholipase C, and di- and monoglyceride lipase, assayed with optimal concentrations of Ca2+ and lysophospholipase, did not significantly change by 60 min of ischemia, whereas acylation enzymes of lysophospholipid decreased in activity to an extent of 70% of control at 15 min after the ischemic treatment. The maximal activities were found at 8 x 10(-3)M, 1 x 10(-3) M, and 2 x 10(-2) M Ca2+ for phospholipase A, phospholipase C, and di- and monoglyceride lipases, respectively in microsomal fractions of both control and ischemic brain. Furthermore, the sensitivity of microsomal enzymes to endogenous Ca2+ was estimated in control and ischemic brain. The sensitivity of phospholipase C was found to be increased after 1 min of ischemic treatment, but those of phospholipase A and di- and monoglyceride lipase were not increased.
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PMID:Activities of enzymes metabolizing phospholipids in rat cerebral ischemia. 274 39

Cerebral ischemia and ischemia-reperfusion induced cerebral injury results in the accumulation of free fatty acids and diacylglycerols as a result of increased activity of phospholipases A and C. We have evaluated the incorporation of 14C arachidonic acid into the whole brain and synaptoneurosomes, the effect of cerebral ischemia on 14C incorporation, and the effect of a PAF antagonist (BN 52021) on cerebral blood flow, free fatty acids, diacylglycerols, and polyphosphoinositides. Peak incorporation of 14C arachidonic acid into the whole brain and synaptoneurosomal fractions occurred 30 minutes following intraventricular injection. Peak incorporation into cerebellar synaptoneurosomal fractions was at 60 minutes following intraventricular injection. Turnover in phospholipid pools was similar in the whole brain and synaptoneurosomes (PI greater than PC greater than PE). Considering phosphatidylinositol content in the gerbil brain, the specific activity of 14C arachidonic acid was 22 times greater in PI than PC. Five minutes of bilateral carotid artery ligation resulted in decreased phosphatidylinositol and polyphosphoinositols. Bilateral carotid artery ligation resulted in systemic arterial hypertension, complete forebrain ischemia (CBF less than 7 ml/100 gm/min) and a 20% to 50% reduction in midbrain CBF. Reperfusion resulted in cerebral reactive hyperemia and systemic hypotension. BN 52021 inhibited the maturation of ischemia-reperfusion induced cerebral injury. Cerebral blood flow was improved. Free fatty acids were decreased, suggesting inhibition of phospholipase A activity. Decreased DAG pools with increased PIP2 pools suggest a possible coinhibition of phospholipase C.
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PMID:Arachidonic acid metabolism and cerebral blood flow in the normal, ischemic, and reperfused gerbil brain. Inhibition of ischemia-reperfusion-induced cerebral injury by a platelet-activating factor antagonist (BN 52021). 277 4

Preincubation of rat myocardial cells in hypoxic substrate-free Krebs-Ringer bicarbonate buffer (pH 7.4, 37 degrees C) resulted in a substantial decline in high energy phosphates (ATP and CP). Thus, 20 and 60 min preincubation produced a 18 and 72% decline in ATP content, whereas the parallel decline in CP content was 51 and 73%. This energy depletion was accompanied by a change in cell morphology from the initial rod-shaped form to rounded up (hyper-contracted) myocytes. In cells preincubated in substrate-free normoxic buffer, both normal morphology and energy homeostasis were maintained. When energy depleted myocytes later were incubated in the presence of phospholipase C (PLC), this resulted in a substantial release of glycerol, amounting to 92 and 137 nmol/10(6) cells.2 h in 20 and 60 min energy depleted myocytes, respectively. In addition, PLC caused an increased leakage of lactate dehydrogenase in energy depleted myocytes. Normal cells, on the other hand, were apparently not affected by PLC. These data suggest that PLC selectively attacks energy depleted and/or structurally damaged myocytes. This could well enhance the breakdown of the natural barrier between the extra- and intracellular compartments and thus augment the cellular damage during ischemia. Moreover, energy depleted myocytes appeared exceptionally sensitive to this enzyme, since the levels required to cause glycerol or lactate dehydrogenase release were several orders of magnitude lower than that required to cause membrane permeation in other cell types.
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PMID:Phospholipase C-evoked glycerol release in energy depleted rat myocardial cells. 277 31

The effect of global ischemia on myocardial ventricular membrane phospholipids was evaluated using a modified Langendorff preparation. Isolated rat hearts were perfused at 37 degrees C with oxygenated Krebs Ringer solution or rendered ischemic by cessation of perfusion (10 min to 3 h). Longer periods of ischemia were assessed by incubating preperfused (10 min) intact hearts in non-oxygenated Krebs (37 degrees C) for 6 to 18 h. Ischemia-induced alterations in phosphatidylinositol levels and phosphoinositide-specific phospholipase C (PI PLC) activity were assessed in detail, since inositol phospholipids and PI-PLC play putative roles in the regulation of cell function and Ca2+ homeostasis. Decreases in major membrane phospholipids (phosphatidylcholine, phosphatidylserine, cardiolipin and sphingomyelin) were demonstrated after long ischemic periods (6 to 18 h). While periods of ischemia (3 h or less) induced no change in structural phospholipids, an elevation in lysophosphatidylcholine and free fatty acids was found by 1 h. Notably a significant increase in phosphatidylinositol content and an accompanying decrease in cytosolic PI PLC activity was detected by 30 mins of ischemia. Reduced enzymic activity was not due to altered in vitro activation or deactivation of PI-PLC, to a change in the Ca2+ requirement of the enzyme, or to translocation of the enzyme from the cytosol to a membrane fraction. The isolated rat heart made globally ischemic for 30 mins under conditions described for this investigation shows signs of irreversible injury i.e. increased cell Ca2+ content and inability to initiate and maintain rhythmic contraction upon reperfusion. Therefore, it is possible that altered phosphoinositide metabolism may contribute to the evolution of ischemia-elicited irreversible cell injury.
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PMID:Alterations in phospholipid metabolism in the globally ischemic rat heart: emphasis on phosphoinositide specific phospholipase C activity. 282 96

In an experimental model of perinatal hypoxic-ischemic brain injury, we examined quisqualic acid (Quis)-stimulated phosphoinositide (PPI) turnover in hippocampus and striatum. To produce a unilateral forebrain lesion in 7-day-old rat pups, the right carotid artery was ligated and animals were then exposed to moderate hypoxia (8% oxygen) for 2.5 h. Pups were killed 24 h later and Quis-stimulated PPI turnover was assayed in tissue slices obtained from hippocampus and striatum, target regions for hypoxic-ischemic injury. The glutamate agonist Quis (10(-4) M) preferentially stimulated PPI hydrolysis in injured brain. In hippocampal slices of tissue derived from the right cerebral hemisphere, the addition of Quis stimulated accumulation of inositol phosphates by more than ninefold (1,053 +/- 237% of basal, mean +/- SEM, n = 9). In contrast, the addition of Quis stimulated accumulation of inositol phosphates by about fivefold in the contralateral hemisphere (588 +/- 134%) and by about sixfold in controls (631 +/- 177%, p less than 0.005, comparison of ischemic tissue with control). In striatal tissue, the corresponding values were 801 +/- 157%, 474 +/- 89%, and 506 +/- 115% (p less than 0.05). In contrast, stimulation of PPI turnover elicited by the cholinergic agonist carbamoylcholine, (10(-4) or 10(-2) M) was unaffected by hypoxia-ischemia. The results suggest that prior exposure to hypoxia-ischemia enhances coupling of excitatory amino acid receptors to phospholipase C activity. This activation may contribute to the pathogenesis of irreversible brain injury and/or to mechanisms of recovery.
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PMID:Perinatal hypoxic-ischemic brain injury enhances quisqualic acid-stimulated phosphoinositide turnover. 283 19


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