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)

Adhesion and recruitment of blood monocytes, processes mediated by cell adhesion molecules including E-selectin, represent an early event in atherogenesis. High density lipoproteins (HDLs) were shown to inhibit cytokine-induced expression of adhesion molecules, but mechanisms underlying this effect are not fully understood. We here investigated the effects of sphingosylphosphorylcholine (SPC) and lysosulfatide (LSF), two lysosphingolipids associated with HDL, on TNF-alpha-induced E-selectin expression in human umbilical endothelial cells. We found that HDL, SPC, and LSF inhibited E-selectin expression both on mRNA and protein level. In addition, all three agents reduced the number of E-selectin molecules present on endothelial cell surface. The inhibitory effects of HDL, SPC, and LSF on TNF-alpha-induced E-selectin expression were partially reverted in the presence of suramin, an antagonist of lysosphingolipid receptor EDG-3, or pertussis toxin, an inhibitor of trimeric G proteins. In addition, inhibition of activation of protein kinase Akt with LY294002 but not inhibition of phosphatidylinositol-specific phospholipase C (PI-PLC) with U73122 abolished the restrictive effects of HDL-, SPC-, or LSF on E-selectin expression. We conclude that HDL-associated lysosphingolipids may at least partially account for the inhibitory effects of HDL on cytokine-induced expression of adhesion molecules, and that activations of G-protein-coupled receptors and protein kinase Akt are involved in this process.
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PMID:High density lipoprotein-associated lysosphingolipids reduce E-selectin expression in human endothelial cells. 1451 54

Calcium entry is one of the main regulators of intracellular signaling. Here, we have described the importance of sphingosine, sphingosine kinase 1 (SK1), and sphingosine 1-phosphate (S1P) in regulating calcium entry in thyroid FRTL-5 cells. In cells incubated with the phosphatase inhibitor calyculin A, which evokes calcium entry without mobilizing sequestered intracellular calcium, sphingosine inhibited calcium entry in a concentration-dependent manner. Furthermore, inhibiting SK1 or the ATP-binding cassette ABCC1 multidrug transporter attenuated calcium entry. The addition of exogenous S1P restored calcium entry. Neither sphingosine nor inhibition of SK1 attenuated thapsigargin-evoked calcium entry. Blocking S1P receptor 2 or phospholipase C attenuated calcium entry, whereas blocking S1P receptor 3 did not. Overexpression of wild-type SK1, but not SK2, enhanced calyculin-evoked calcium entry compared with mock-transfected cells, whereas calcium entry was decreased in cells transfected with the dominant-negative G82D SK1 mutant. Exogenous S1P restored calcium entry in G82D cells. Our results suggest that the calcium entry pathway is blocked by sphingosine and that activation of SK1 and the production of S1P, through an autocrine mechanism, facilitate calcium entry through activation of S1P receptor 2. This is a novel mechanism by which the sphingosine-S1P rheostat regulates cellular calcium homeostasis.
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PMID:Sphingosine kinase as a regulator of calcium entry through autocrine sphingosine 1-phosphate signaling in thyroid FRTL-5 cells. 1979 3