Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Individual and pooled samples of plasma from normolipemic and hyperlipemic subjects were separated into very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein fractions (HDL2 and HDL3) by conventional ultracentrifugation and total lipid extracts prepared by standard methods. The composition of the molecular species of the sphingomyelins in each lipoprotein class was determined by packed column and capillary gas-liquid chromatography of the trimethylsilyl (TMS) and t-butyldimethylsilyl (t-BDMS) ethers and by gas chromatography - mass spectrometry of t-BDMS ethers of ceramides derived by phospholipase C hydrolysis of the corresponding parent compounds. It was demonstrated that the molecular weight of the species of the sphingomyelins increases with the density of the lipoprotein fraction in normolipemic subjects, and that this increase is due to an increase in the chain length of the fatty acids in the ceramide molecules. In contrast, patients with type IV hyperlipoproteinemia possessed similar species in the LDL and HDL fractions, while maintaining normal differences between HDL and VLDL. Type III patients possessed normal HDL and VLDL differences, but had variable LDL. Type II patients had ceramide profiles for VLDL, LDL, and HDL fractions that were very similar to those of normals. The differential distribution of the molecular species of the sphingomyelins is rationalized on the basis of a lateral phase separation of the short and long chain sphingomyelins during the shedding of the excess VLDL or chylomicron surface material and a subsequent preferential transformation of the long chain species into HDL. The LDL sphingomyelins in type III hyperlipemia are variable and approximate either the VLDL or HDL composition.
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PMID:Differential distribution of sphingomyelins among plasma lipoprotein classes. 729 45

Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that regulates numerous key cardiovascular functions. High-density lipoproteins (HDLs) are the major plasma lipoprotein carriers of S1P. Fibrinolysis is a physiological process that allows fibrin clot dissolution, and decreased fibrinolytic capacity may result from increased circulating levels of plasminogen activator inhibitor-1 (PAI-1). We examined the effect of S1P associated with HDL subfractions on PAI-1 secretion from 3T3 adipocytes. S1P concentration in HDL3 averaged twice that in HDL2. Incubation of adipocytes with increasing concentrations of S1P in HDL3, but not HDL2, or with S1P complexed to albumin stimulated PAI-I secretion in a concentration-dependent manner. Quantitative RT-PCR revealed that S1P(1-3) are expressed in 3T3 adipocytes, with S1P(2) expressed in the greatest amount. Treatment of adipocytes with the S1P(1) and S1P(3) antagonist VPC23019 did not block PAI-1 secretion. Inhibiting S1P(2) with JTE-013 or reducing the expression of the gene coding for S1P(2) using silencing RNA (siRNA) technology blocked PAI-1 secretion, suggesting that the S1P(2) receptor mediates PAI-1 secretion from adipocytes exposed to HDL3 or S1P. Treatment with the phospholipase C (PLC) inhibitor U73122, the protein kinase C (PKC) inhibitor RO-318425, or the Rho-associated protein kinase (ROCK) inhibitor Y27632 all significantly inhibited HDL3- and S1P-mediated PAI-1 release, suggesting that HDL3- and/or S1P-stimulated PAI-1 secretion from 3T3 cells is mediated by activation of multiple, downstream signaling pathways of S1P(2).
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PMID:HDL3, but not HDL2, stimulates plasminogen activator inhibitor-1 release from adipocytes: the role of sphingosine-1-phosphate. 2052 1