Platelet-activating factor production in the spinal cord of experimental allergic encephalomyelitis mice via the group IVA cytosolic phospholipase A2-lyso-PAFAT axis.
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Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) plays a critical role in inflammatory disorders including experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Although PAF accumulation in the spinal cord (SC) of EAE mice and cerebrospinal fluid of MS patients has been reported, little is known about the metabolic processing of PAF in these diseases. In this study, we demonstrate that the activities of phospholipase A(2) (PLA(2)) and acetyl-CoA:lyso-PAF acetyltransferase (LysoPAFAT) are elevated in the SC of EAE mice on a C57BL/6 genetic background compared with those of naive mice and correlate with disease severity. Correspondingly, levels of groups IVA, IVB, and IVF cytosolic PLA(2)s, group V secretory PLA(2), and LysoPAFAT transcripts are up-regulated in the SC of EAE mice. PAF acetylhydrolase activity is unchanged during the disease course. In addition, we show that LysoPAFAT mRNA and protein are predominantly expressed in microglia. Considering the substrate specificity and involvement of PAF production, group IVA cytosolic PLA(2) is likely to be responsible for the increased PLA(2) activity. These data suggest that PAF accumulation in the SC of EAE mice is profoundly dependent on the group IVA cytosolic PLA(2)/LysoPAFAT axis present in the infiltrating macrophages and activated microglia. (+info)
Mitochondrial and microsomal phospholipids of Morris hepatoma 7777.
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The phospholipids of both mitochondrial and microsomal membranes from normal liver, host liver, and Morris hepatoma 7777 were isolated, separated, and quantitated. The total as well as the individual fatty acid concentrations and compositions were determined. The total phosphlipids isolated from tumor mitochondria were idly altered, compared with mitochondria from other normal or host liver. The polyenoic acids were decreased, and there was a concomitant increase in the monoenes. When the respiratory control was determined, the tumor mitochondria exhibited a significant decrease in this parameter. The tumor microsomal membrane fraction, on the other hand, contained about 50% less phospholipid than the controls. The fatty acid patterns of the total as well as the individual phospholipids were quite similar to those observed in the mitochondria. The species of phosphatidylcholine from both membrane fractions were separated by argentation chromatography of the intact molecules, and, as predicted by the fatty acid compositions, the major species of the tumor was the monoenoic/dienoic fraction. The acyl coenzyme A:1-acyl glycerophosphorylcholine acyltransferases, which aid in controlling the fatty acid composition of phospholipids, were measured. The very marked increase in activity of these enzymes toward polyenoic as well as monoenic fatty acids suggested that the polyenoic acids were not available for use in the resynthesis of the phosphatidylcholines in the tumor. (+info)
Recent progress on acyl CoA: lysophospholipid acyltransferase research.
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