Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Depletion of membrane phospholipids is known to be associated with myocardial ischemia, but its relationship to the injury involved with the reperfusion of ischemic myocardium is not known. The present study was designed to relate phospholipid degradation with reperfusion injury. The isolated in situ pig heart was subjected to 60 min of regional ischemia induced by occluding the left anterior descending (LAD) coronary artery and 60 min of global ischemia by hypothermic cardioplegic arrest followed by 60 min of reperfusion. The pigs were divided into two groups. In the treatment group, the heart was preperfused with mepacrine (0.05 mM), a known phospholipase inhibitor, for 15 min prior to LAD occlusion. In the control group, the total phospholipid content was not significantly decreased during LAD occlusion and arrest, but was reduced appreciably after reperfusion. Phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol followed a similar pattern. The lowering of these phospholipids during reperfusion was accompanied by enhancement of lysophosphatidylcholine. Mepacrine restored the normal levels of these phospholipids. During reperfusion, fatty acyl CoA synthetase, lysophospholipase, and lysophosphatidylcholine acyltransferase were depressed, whereas phospholipase A2 was enhanced. Mepacrine inhibited phospholipase A2, but had no effects on the other enzymes. Mepacrine also provided significant protection against reperfusion injury, as documented by the preservation of high-energy phosphate compounds and inhibition of the appearance of creatine kinase activity in the perfusate. These results suggest that membrane phospholipids play an important role in myocardial injury associated with ischemia and reperfusion, primarily because the deacylation-reacylation cycle of phospholipid biosynthesis becomes defective.
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PMID:Role of membrane phospholipids in myocardial injury induced by ischemia and reperfusion. 294 42

During myocardial ischemia increased levels of lysoglycerophospholipids have been reported which may be deleterious to myocardial function. Phospholipases are presumed to be important in the regulation of this process. To further quantify and characterize the activity of heart phospholipases, we carried out a systematic analysis of phospholipase A activity in rat heart subcellular fractions isolated by the method of Palmer et al. (J. Biol. Chem. 1972. 262: 8731-8739). Neutral phospholipase A was recovered predominately in the cytosolic (soluble) fraction which represented 46% of recovered activity, while the microsomal and subsarcolemmal mitochondrial fractions represented 15% and 12% of the total recovered activity, respectively. Cytosolic phospholipase A differed from the two principal membrane-bound phospholipases A in its pH dependence and apparent Km for substrate. The cytosolic enzyme had a Km (apparent) for dioleoylphosphatidylcholine of 0.07 mM versus 0.28-0.33 mM for the membrane-associated phospholipases A. Acid phospholipase A activity had a subcellular distribution consistent with a lysosomal localization. Lysophospholipase was found principally in the cytosolic, microsomal, and the subsarcolemmal and interfibrillar mitochondrial fractions where it represented 46, 17, 6.3, and 6.9% of the recovered activity, respectively. The positional specificity of the respective phospholipases was assessed. This analysis was complicated by the fact that in heart, lysophospholipase has an observed Vmax 3.6- to 4.5-fold greater than that of phospholipase A in the various subcellular fractions. Equations were derived to obtain corrected values for the activity of phospholipases A1 and A2. Using this method we found that the cytosolic and lysosomal fractions contained phospholipase A1, while the mitochondrial fractions contained primarily phospholipase A2. In heart microsomes, the positional specificity of phospholipase A could not be determined because lysophospholipase activity was very high and lysophosphatidylcholine did not accumulate.
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PMID:Subcellular localization of the phospholipases A of rat heart: evidence for a cytosolic phospholipase A1. 391 32

Enzymatic pathways involved in the metabolism of lysophosphatidylcholine were investigated in rat heart myocardial cells. Acyl CoA-dependent acyltransferase activity was localized in microsomes, and was much greater than lysophospholipase activity in either cytosolic or microsomal fractions. The cytosolic lysophospholipase was more sensitive to inhibition by palmitylcarnitine in comparison to free fatty acids. In contrast, free fatty acids (oleate and palmitate) produced a greater inhibition of the microsomal acyltransferase and lysophospholipase than did palmitylcarnitine. A reduction in the assay pH to 6.5 resulted in an increase in microsomal acyltransferase and cytosolic lysophospholipase activities, but brought about a marked reduction in the microsomal lysophospholipase activity. At pH 6.5, the percentage inhibition of the microsomal acyltransferase by palmitylcarnitine was reduced, whereas the inhibition by palmitic acid was enhanced. The inhibition of the microsomal lysophospholipase by both palmitylcarnitine and palmitic acid was reduced at pH 6.5. With respect to myocardial ischemia, the inhibition of microsomal acyltransferase by free fatty acids and the reduction in microsomal lysophospholipase activity due to acidosis may contribute to the elevation of cellular lysophosphoglycerides which are arrhythmogenic.
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PMID:Regulation of lysophosphatidylcholine-metabolizing enzymes in isolated myocardial cells from rat heart. 407 68

Since lysophosphatides have been implicated as arrhythmogenic metabolites, modulation of their catabolism in cardiac myocytes has been characterized. Rat cardiac myocytes and mesenchymal cells grown in culture were found to contain cytosolic lysophospholipase with specific activities of 1.3 +/- 0.1 and 0.9 +/- 0.1 nmol X mg-1 X min-1, respectively. Rat myocytic lysophospholipase had a molecular mass of approximately 20,000 daltons, estimated by gel filtration chromatography. Kinetic analysis of cytosolic myocytic lysophospholipase demonstrated a Michaelis constant of 11 microM, a pH optimum of 8.0, and competitive inhibition by L-palmitoyl carnitine (inhibitory constant of 12 microM). Although lysophospholipase-transacylase activity could not be detected in rat myocyte or mesenchymal cell cultures, rabbit myocytes isolated by perfusion of isolated hearts with collagenase contained lysophospholipase-transacylase in cytosolic extracts with a specific activity of 0.2 nmol X mg-1 X min-1. These results demonstrate the presence of lysophospholipase in cardiac myocytes and suggest that the increase in long-chain acyl carnitine, which occurs during myocardial ischemia, may contribute to accumulation of lysophosphatides within cardiac myocytes.
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PMID:Cytosolic lysophospholipase in cardiac myocytes and its inhibition by L-palmitoyl carnitine. 670 40

Lysophosphatidylcholine accumulates in the coronary sinus during pacing-induced myocardial ischemia in humans. This amphiphile accelerates Ca++ flux leading to cell injury in cultured cardiac myocytes, but it is not known whether lysophosphatidylcholine accumulation is injurious to human myocardium. In this study, we measured lysophosphatidylcholine in normal human myocardium obtained during cardiac surgery and exposed to ischemic conditions in vitro. Total lysophosphatidylcholine concentration (sum of lysophosphatidylcholine remaining in tissue and lysophosphatidylcholine released into the buffer) increased from 0.73 +/- 0.08 nmol/mg protein at baseline to 1.83 +/- 0.45 nmol/mg protein after 5 minutes of ischemia (p < 0.001), and was associated with evidence of cell injury (26% depletion of tissue lactate dehydrogenase). Significant lysophosphatidylcholine release into the incubation buffer (0.41 +/- 0.11 nmol/mg protein) also occurred after 5 minutes of ischemia. In contrast, there was no lysophosphatidylcholine accumulation or release and no lactate dehydrogenase depletion in oxygenated and perfused controls. Attenuation of lysophosphatidylcholine accumulation by incubation with lysophospholipase did not prevent cell injury. Lysoplasmalogen was not detected in ischemic tissue. We conclude that lysophosphatidylcholine accumulation is a marker of myocardial ischemia in humans.
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PMID:Lysophosphatidylcholine accumulation in ischemic human myocardium. 842 72