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)

Amiodarone is used extensively for the chronic treatment of life-threatening arrhythmias caused by ischemic heart disease. However, chronic therapy with this agent results in phospholipidosis in various tissues and it has been suggested that the inhibition of lysosomal phospholipase A by this drug contributes to this abnormality. Exogenous amiodarone has been shown to inhibit purified rat liver lysosomal phospholipase A1, as well as acid phospholipase activities of alveolar macrophage homogenates and those of snake venom phospholipase A2 and bacterial phospholipase C. The effects of drug treatment on heart have not been explored. The results described here demonstrate that amiodarone also significantly increases (37%, p less than 0.001) phospholipid content in cat hearts. This increase is proportionately distributed to all major phospholipid classes, with the exception of sphingomyelin which appears to increase more than the others. In addition, the data also show that following amiodarone treatment, the endogenous drug levels in the heart were sufficient to reduce in vitro losses of membrane phospholipid at 37 degrees C by inhibiting a variety of endogenous phospholipases at physiological (7.4), ischemic (6.2) and acidic (5.0) pH values. This protection is more pronounced at acidic pH values than at physiological pH. Endogenous amiodarone also affects myocardial phospholipase activities towards exogenous phosphatidylcholine and again the extent of inhibition is more at acidic pH. These results suggest that amiodarone induces phospholipidosis in the heart by inhibiting phospholipid catabolism and that its antiarrhythmic properties may reside in its ability to modulate alkaline, neutral and acid phospholipase activities in ischemia. To what extent amiodarone metabolites (desethylamiodarone and bis-desethylamiodarone) are involved in these actions remains to be determined.
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PMID:Effects of chronic amiodarone treatment on cat myocardial phospholipid content and on in vitro phospholipid catabolism. 345 65

The purpose of our study was to examine the ischemia induced enzymatic changes of decaylation-reacylation cycle of membrane phospholipids in dog brain. In this study, we developed new modified method for assay of phospholipase A1, A2 and lysophospholipase which is simpler and needs only a smaller amount of materials. For the first report, we introduced this new method and demonstrated some properties of phospholipase A1, A2 and lysophospholipase in dog brain. Crude enzyme solution for assays of phospholipase A1, A2 and lysophospholipase was gained from extraction of frozen brain with aceton, butanol and saline. The level of phosphorus in the enzyme extract was determined and only those extracts which had a level of phosphorus within a certain range were used. The substrates for assays were L-alpha-[beta-palmitoyl-1-14C] phosphatidylcholine, dipalmitoyl for phospholipase A1 and A2 and L-lysophosphatidylcholine-1-[1-14C] palmitoyl for lysophospolipase respectively. Each radioactive substrates was diluted with cold carrier lipid to give the proper specific activity. Reaction system including substrate, buffer [pH 7.0] and enzyme extract was incubated for 10 hours at 38 degrees C. But for the assay of phospholipase A1 and A2, enzyme solution was pre-incubated at 70 degrees C for 5 minutes. In our new method, reaction mixture was directly separated by TLC without extracting lipids. Enzyme activities were calculated from radio thin-layer chromatograms. Furthermore, we made a comparison between our method and the former one. The value of each enzyme activity was slightly higher in our method than in the former one. However, it was revealed that the results were reproducible in both methods.
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PMID:[Simplified microdetermination of cerebral phospholipase A1, A2 and lysophopholipase]. 663 6

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

Extracts of acetone-dried powders from ischemic gerbil brain were examined for phospholipase A1 and A2 activities with phosphatidylethanolamine at pH 7.2. Ischemia was induced by bilateral ligation, and the animals were killed by immersion into liquid nitrogen. Bilateral ligation with ketamine as general anesthetic resulted in a rapid, transient increase in phospholipase A2 activity. The activity increased from 0.46 nmol/h/mg protein at 0 time to 0.82 nmol/h/mg protein at 1 min of ligation. Phospholipase A1 activity also increased from 0.7 go 1.3 nmol/h/mg protein within the 1st min. When Nembutal was used as anesthetic, the phospholipase activation was earlier, within the first 30 s. Similar results were found for ischemia induced by decapitation of Wistar rats without anesthesia. Bilateral ligation of the carotid arteries of the gerbil is known to increase the concentration of free fatty acids, particularly arachidonate. This increase is, at least in part, due to phospholipase A activation. As ethanolamine phospholipase A2 in brain does not require Ca2+ for activity, these results suggest that phospholipase A2 activation in ischemic brain results from a covalent modification of the enzyme.
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PMID:Activation of ethanolamine phospholipase A2 in Brain during ischemia. 711 83