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)

Pretreatment of the ischemic myocardium with verapamil protects against mitochondrial respiratory depression observed during ischemic arrest as well as during reperfusion. Since ischemic mitochondrial function appears not to be altered further by reperfusion, the purpose of this study is to identify a biochemical event affecting mitochondria that is specifically associated with reperfusion injury. It has been proposed that increased cellular Ca2+ influx and oxygen toxicity may result from reintroduction of coronary flow. Increased cytosolic Ca2+ is transmitted to the mitochondria with subsequent activation of Ca2+-dependent events, including phospholipase A2. Net production of lysophospholipids (and loss of total diacylphospholipids from the mitochondria) will proceed when reacylation mechanisms are inhibited. Since acyl-CoA:lysophospholipid acyltransferase is a sulfhydryl-sensitive enzyme and since increased activity of glutathione peroxidase shifts the levels of the mitochondrial sulfhydryl buffer, glutathione, towards oxidation, levels of glutathione and its oxidation state were measured during reperfusion in the absence or presence of verapamil pretreatment. Ischemia lowers total glutathione and reduces the redox ratio (reduced glutathione: oxidized glutathione) by 85%. Reperfusion partially returns the redox ratio to control by causing oxidized glutathione to disappear from the matrix. Verapamil maintains both the concentration and the redox potential of glutathione at control levels. Concomitant with alterations in reduced glutathione:oxidized glutathione is a decrease in ischemic mitochondrial phospholipid content. During reperfusion, phosphatidylethanolamine and its major constituent fatty acids (C 18:0 and C 20:4) are specifically lost from the mitochondrial membrane. Accompanying the significant loss of arachidonic acid during reperfusion is the decreased content of 11-OH, 12-OH, and 15-OH arachidonate. These lipid peroxidation products are not increased in ischemia. It is proposed that oxidation of matrix glutathione to glutathione disulfide during ischemia results in formation of glutathione-protein mixed disulfides and inhibition of sulfhydryl-sensitive proteins, including acyl-CoA lysophosphatide acyltransferase. Thus, metabolic events occurring within the ischemic period set the stage for prolonged dysfunction during reperfusion.
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PMID:Protection by verapamil of mitochondrial glutathione equilibrium and phospholipid changes during reperfusion of ischemic canine myocardium. 362 93

It is generally known that free fatty acids (FFA) are liberated from membrane phospholipids in the brain tissue during the early period of ischemia. However, the precise mechanism of FFA liberation from phospholipids is still unclear, even though it is a central topic of neurosurgery. As an initial step toward a better understanding of the molecular mechanism, we have investigated the effects of global ischemia upon brain lipid metabolism. Brain ischemia was evoked by rat decapitation without anesthesia. Removed brains were incubated for 1, 5, 15 or 30 min at 37 degrees C and then quickly frozen in liquid nitrogen. After extraction of total lipids from the brains by Bligh & Dyer's method, the compositions of neutral lipids and phospholipids were analyzed by thin-layer and gas-liquid chromatography. For assaying deacylating enzyme (phospholipase A) activity, the brain homogenate was used as a crude enzyme. The reaction mixture including radioactive substrate, buffer (pH 7.3 & 4.0) and enzyme was incubated for 1 hour at 37 degrees C. Lipids were extracted from reaction mixture and separated by TLC. The enzyme activity was estimated by measuring the radioactivity in FFA or lysophosphatidylcholine liberated from L-alpha-di [1-14C] palmitoyl phosphatidylcholine. The reaction mixture for the assay of reacylating enzyme (acyl CoA: lysophospholipid acyltransferase) activity, contained acyl CoA, lysophosphatidylcholine, DTNB and microsomes, and the enzyme activity was determined by the amount of released CoA-SH detected spectrophotometrically. The results demonstrated that FFA, either unsaturated or saturated, rapidly accumulated in the brain during the early period of ischemia. Di-acylglycerols were also produced in the ischemic brain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Brain lipid metabolism during early period of global ischemia--with reference to the enzymes related to membrane phospholipid metabolism]. 402 85

It has been well recognized that acyl groups of phospholipids play an important role for structure and function of biomembrane. The turnover of these acyl groups in normal brain biomembrane is also well known. Some types of enzymic system related to this turnover has been investigated. Phospholipase A, PI-specific phospholipase C, lipase, lysophospholipase and acylCoA: lysophospholipid acyltransferase belong to these enzymic systems. In this report, the sequential changes of phospholipase A, PI-specific phospholipase C, lipase, lysophospholipase and acylCoA: lysophospholipid acyltransferase activities in ischemic rat brain were examined. The purpose of this study was to examine the enzymic changes of deacylation-reacylation cycle of biomembrane phospholipid in ischemic brain. Ischemic brain were produced by decapitation and activities of 5 enzymes were assayed in microsomal fraction. The activities of phospholipase A, PI-specific phospholipase C, lipase showed high value during early stage of ischemia for 15 or 30 min and then decreased gradually. Lysophospholipase activity was not changed for 120 min. On the other hand, acylCoA: lysophospholipid acyltransferase activity showed gradual decrease from the beginning of ischemia. There are some reports that in early ischemic stage, the concent of free fatty acids increase, while that of phospholipid decrease. The present results may suggest that the changes of free fatty acid and phospholipid in ischemic brain are related to these enzymic system.
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PMID:[The activities of phospholipase A, PI-specific phospholipase C, lipase, lysophospholipase and acylCoA: lysophospholipid acyltransferase in ischemic brain microsomal fraction]. 402 86

In this report, the sequential changes of phospholipase A1, A2, lysophospholipase and acylCoA: lysophospholipid acyltransferase activities in ischemic dog brain were investigated. The purpose of this study was to examine the enzymic changes of deacylation-reacylation cycle of biomembrane phospholipid in ischemia. Hemispheric non-blood supply models were produced by occlusion of main intracranial trunk arteries in dogs according to Suzuki's method. The sample was spooned out and frozen immediately with liquid nitrogen at the predetermined time. The assay of phospholipase A1, A2 and lysophospholipase activities was done by our method and acylCoA: lysophospholipid acyltransferase activity was according to Corbin and Sun's method. The activities of phospholipase A1, A2 and lysophospholipase did not show significant changes within 60 minutes after arterial occlusion. However these activities showed significant high value at 120 minutes and decreased gradually after then. On the other hand, acylCoA: lysophospholipid acyltransferase activity showed gradual decrease. These findings show that enzymic degradiation of acyl group of phospholipid in the brain is highest at about 120 minutes after complete ischemia. The importance of acyl groups of phospholipids for biomembrane structure and the function is well recognized. The turnover of these acyl groups in normal brain biomembrane is also well known. Some types of enzymic system related to this turnover has been investigated. Phospholipase A1, A2, lysophospholipase and acylCoA: lysophospholipid acyltransferase belong to these enzymic systems. There have been some reports that the content of free fatty acids in the ischemic brain increases in early stage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Activities of phospholipase A1, A2, lysophospholipase and acylCoA: lysophospholipid acyltransferase in ischemic brain of the dog]. 665 88

Under physiological conditions, the content of unesterified arachidonic acid in cardiac tissue is very low. The bulk of arachidonic acid is present in the membrane phospholipid pool. Incorporation of arachidonic acid into phospholipids (reacylation) and liberation of this fatty acid from the phospholipid pool (deacylation) are controlled by a set of finely tuned enzymes, including lysophospholipid acyltransferase and phospholipase A2. At present, at least three subtypes of phospholipase A2 have been identified in cardiac structures, i.e., a low molecular mass group II phospholipase A2, a cytoplasmic high molecular mass phospholipase A2 and a plasmalogen-specific phospholipase A2. Cessation of flow to the heart (ischemia) gives rise to net degradation of membrane phospholipids accompanied by accumulation of fatty acids, including (unesterified) arachidonic acid. Restoration of flow to the previously ischemic cells results in a continued accumulation of fatty acids. The mechanism(s) underlying net phospholipid degradation in ischemic/reperfused myocardial tissue is (are) incompletely understood. Impaired reacylation, enhanced hydrolysis of phospholipids, or a combination of both may be responsible for the phenomena observed. Elevated tissue levels of arachidonic acid may exert both direct and indirect effects on the affected myocardium and healthy cardiac cells adjacent to the injured cardiomyocytes. Indirect effects might be evoked by arachidonic acid metabolites, i.e., eicosanoids. Arachidonic acid may directly influence ion channel activity, substrate metabolism and signal transduction, thereby affecting the functional characteristics of the ischemic/reperfused myocardium.
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PMID:Accumulation of arachidonic acid in ischemic/reperfused cardiac tissue: possible causes and consequences. 925 Jun 13

The deacylation-reacylation cycle is an important mechanism responsible for the introduction of polyunsaturated fatty acids into neural membrane glycerophospholipids. It involves four enzymes, namely acyl-CoA synthetase, acyl-CoA hydrolase, acyl-CoA: lysophospholipid acyltransferase, and phospholipase A2. All of these enzymes have been purified and characterized from brain tissue. Under normal conditions, the stimulation of neural membrane receptors by neurotransmitters and growth factors results in the release of arachidonic acid from neural membrane glycerophospholipids. The released arachidonic acid acts as a second messenger itself. It can be further metabolized to eicosanoids, a group of second messengers involved in a variety of neurochemical functions. A lysophospholipid, the second product of reactions catalyzed by phospholipase A2, is rapidly acylated with acyl-CoA, resulting in the maintenance of the normal and essential neural membrane glycerophospholipid composition. However, under pathological situations (ischemia), the overstimulation of phospholipase A2 results in a rapid generation and accumulation of free fatty acids including arachidonic acid, eicosanoids, and lipid peroxides. This results in neural inflammation, oxidative stress, and neurodegeneration. In neural membranes, the deacylation-reacylation cycle maintains a balance between free and esterified fatty acids, resulting in low levels of arachidonic acid and lysophospholipids. This is necessary for not only normal membrane integrity and function, but also for the optimal activity of the membrane-bound enzymes, receptors, and ion channels involved in normal signal-transduction processes.
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PMID:Deacylation and reacylation of neural membrane glycerophospholipids. 1098 88