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)

The role of nuclear membrane phospholipids as targets of phospholipases resulting in the generation of nuclear signaling messengers has received attention. In the present study, we have exploited the utility of electrospray ionization mass spectrometry to determine the phospholipid content of nuclei isolated from perfused hearts. Rat heart nuclei contained choline glycerophospholipids composed of palmitoyl and stearoyl residues at the sn-1 position with oleoyl, linoleoyl, and arachidonoyl residues at the sn-2 position. Diacyl molecular species were the predominant molecular subclass in the choline glycerophospholipids, with the balance of the molecular species being plasmalogens. In the ethanolamine glycerophospholipid pool from rat heart nuclei approximately 50% of the molecular species were plasmalogens, which were enriched with arachidonic acid at the sn-2 position. A 50% loss of myocytic nuclear choline and ethanolamine glycerophospholipids was observed in hearts rendered globally ischemic for 15 min followed by 90 min of reperfusion in comparisons with the content of these phospholipids in control perfused hearts. The loss of nuclear choline and ethanolamine glycerophospholipids during reperfusion of ischemic myocardium was partially reversed by the calcium-independent phospholipase A(2) (iPLA(2)) inhibitor bromoenol lactone (BEL), suggesting that the loss of nuclear phospholipids during ischemia/reperfusion is mediated, in part, by iPLA(2). Western blot analyses of isolated nuclei from ischemic hearts demonstrated that iPLA(2) is translocated to the nucleus after myocardial ischemia. Taken toghether, these studies have demonstrated that nuclear phospholipid mass decreases after myocardial ischemia by a mechanism that involves, at least in part, phospholipolysis mediated by iPLA2.
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PMID:Electrospray ionization mass spectrometry analyses of nuclear membrane phospholipid loss after reperfusion of ischemic myocardium. 1101

Myocardial function is intimately dependent on the precise spatiotemporal regulation of membrane-bound proteins and ion channels. Phospholipases play critical roles in the maintenance of membrane structure and function, thereby fundamentally integrating dynamic alterations in myocardial performance with membrane composition and dynamics. The major phospholipases in myocardium belong to a family of proteins known as calcium-independent phospholipases (iPLA2s). In addition to their role in maintaining normal membrane structure and function, iPLA2 catalytic activity results in the generation of a variety of lipid second messengers that facilitate cellular signaling. Through its multiple effects on cardiac myocyte bioenergetics, cellular signaling, and membrane function, the iPLA2 family of enzymes is of primary importance in modulating the pathologic sequelae of myocardial ischemia, diabetic cardiomyopathy, and remodeling during hemodynamic stress. This review will provide a brief overview of myocardial iPLA2s and their significance in cardiac pathology and physiology.
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PMID:Calcium-independent phospholipases in the heart: mediators of cellular signaling, bioenergetics, and ischemia-induced electrophysiologic dysfunction. 1939 Mar 46

Caspase-independent, non-apoptotic cell death is an important therapeutic target in myocardial ischemia. Leptin, an adipose-derived hormone, is known to exhibit cytoprotective effects on the ischemic heart, but the mechanisms are poorly understood. In this research, we found that pretreatment of leptin strongly suppressed ischemic-augmented nuclear shrinkage and non-apoptotic cell death on cardiomyocytes. Leptin was also shown to significantly inhibit the activity of iPLA2, which is considered to play crucial roles in non-apoptotic cell death, resulting in effective prevention of ischemia-induced myocyte death. These findings provide the first evidence of a protective mechanism of leptin against ischemia-induced non-apoptotic cardiomyocyte death.
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PMID:Leptin suppresses non-apoptotic cell death in ischemic rat cardiomyocytes by reduction of iPLA(2) activity. 2597 60