Search results for "phosphodiester"
showing 10 items of 176 documents
Sphingomyelin inhibition of Ciona intestinalis (Tunicata) cytotoxic hemocytes assayed against sheep erythrocytes
1995
Hemocytes from the ascidian, Ciona intestinalis, are capable of lysing erythrocytes in vitro following cell membrane contact. With the aim of examining the mechanism of cytotoxicity, we performed inhibition experiments with lipid components of erythrocyte membranes. Cholesterol is not an inhibitor, whereas, among the phospholipids tested, (sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine) sphingomyelin inhibits the hemolytic activity of hemocytes. However, thin layer chromatography showed that sphingomyelinase activity was not contained in the chloroform-methanol extracts from hemocyte debris. The inhibition capacity of the components ceramide and phosphorylc…
Induction of programmed cell death in human retinoblastoma Y79 cells by C2-ceramide.
1998
C2-ceramide, a cell-permeable analogue of ceramide, induced significant, dose- and time-dependent death in human retinoblastoma Y79 cells. Dying cells strongly displayed the morphology of apoptosis as characterized by microscopic evidence of cell shrinkage, membrane blebbing, nuclear and chromatin condensation and degeneration of the nucleus into membrane-bound apoptotic bodies. Upon induction of apoptosis Y79 cells evidence early phosphatidylserine externalization, as shown by annexin V-FITC. Apoptosis was also assessed by monitoring changes in cell granularity by staining with the combined fluorescent dyes acridine orange and ethidium bromide. C2-ceramide induced these morphological chang…
Regulation of cyclooxygenase-2 expression by cyclic AMP.
2007
Abstract Prostaglandins (PG) regulate many biological processes, among others inflammatory reactions. Cyclooxygenases-1 and -2 (COX-1 and COX-2) catalyse PG synthesis. Since this step is rate limiting, the regulation of COX expression is of critical importance to PG biology. Contrary to COX-1, which is constitutively expressed, COX-2 expression is subject to regulation. For example, COX-2 levels are increased in inflammatory reactions. Many signalling pathways can regulate COX-2 expression, not least those involving receptors for COX products themselves. Analysis of the intracellular signal transducers involved reveals a crucial role for cAMP, albeit as a modulator rather than direct induce…
Production of ceramides causes apoptosis during early neural differentiation in vitro.
2000
To investigate signal transduction pathways leading to apoptosis during the early phase of neurogenesis, we employed PCC7-Mz1 cells, which cease to proliferate and begin to differentiate into a stable pattern of neurons, astroglial cells, and fibroblasts upon incubation with retinoic acid (RA). As part of lineage determination, a sizable fraction of RA-treated cultures die by apoptosis. Applying natural long-chain C(16)-ceramides as well as membrane-permeable C(2)/C(6)-ceramide analogs caused apoptosis, whereas the biologically nonactive C(2)-dihydroceramide did not. Treating PCC7-Mz1 stem cells with a neutral sphingomyelinase or with the ceramidase inhibitor N-oleoylethanolamine elevated t…
Ceramide Mediates Acute Oxygen Sensing in Vascular Tissues
2014
AbstractAims: A variety of vessels, such as resistance pulmonary arteries (PA) and fetoplacental arteries and the ductus arteriosus (DA) are specialized in sensing and responding to changes in oxygen tension. Despite opposite stimuli, normoxic DA contraction and hypoxic fetoplacental and PA vasoconstriction share some mechanistic features. Activation of neutral sphingomyelinase (nSMase) and subsequent ceramide production has been involved in hypoxic pulmonary vasoconstriction (HPV). Herein we aimed to study the possible role of nSMase-derived ceramide as a common factor in the acute oxygen-sensing function of specialized vascular tissues. Results: The nSMase inhibitor GW4869 and an anticera…
Streptolysin O-permeabilized granulocytes shed L-selectin concomitantly with ceramide generation via neutral sphingomyelinase
2000
Abstract Cleavage of membrane-associated L-selectin regulates leukocyte rolling on vascular endothelium at sites of inflammation. We report that rapid and massive shedding of L-selectin occurs from granulocytes attacked by the pore-forming bacterial toxin streptolysin O (SLO). Shedding was not induced by an SLO mutant that retained binding capacity but lacked pore-forming activity. Cells permeabilized with SLO exhibited a 1.5-fold increase in the activity of neutral sphingomyelinase, which was accompanied by increased ceramide formation. L-selectin cleavage was inducible by treatment of cells with bacterial sphingomyelinase, and also through exogenous application of a cell-permeable ceramid…
Organotin(IV) chloride complexes with phosphocholine and dimyristoyl-L-?-phosphatidylcholine
2000
Several complexes of R n SnCl 4-n (R = Me, Ph, n = 1-3; R = nBu, n = 2, 3) with phosphocholine and dimyristoyl-L-α-phosphatidylcholine (phospholipid) have been synthesized and characterized by means of Mossbauer spectroscopy and NMR. Triorganotin chlorides form complexes of (R 3 SnCl) 2 .L stoichiometry with a trigonal bipyramidal pentacoordinate tin environment, while the others form 1:1 complexes with an octahedral hexacoordinate tin environment, with the ligands coordinating through anionic phosphodiester moieties in all cases.
Effects of the Phosphodiesterase Inhibitor Enoximone on the Autonomic Innervation of the Isolated Heart
1989
Enoximone is a selective inhibitor of a low Km, cyclic AMP-specific type of phosphodiesterase (PDE III). In guinea pig and chicken atria, enoximone (0.1-100 mumol/L) caused a weak increase in the force of contraction. The heart rate was slightly enhanced or was unchanged (chicken). Enoximone (30 mumol/L) also failed to shift the concentration-response curves for the positive inotropic and chronotropic effects of norepinephrine in guinea pig atria. Under almost the same conditions, enoximone and the nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) markedly potentiated the forskolin-induced mobilization of choline from phospholipids. The concentrations of IBMX (100 mumol/L) and o…
Reliability of Virtual Screening Methods in Prediction of PDE4Binhibitor Activity
2015
Identification of active ligands using computational methods is a challenging task. For example, molecular docking, pharmacophore modeling, and three dimensional quantitative structure-activity relationship models (3D-QSAR) are widely used methods to identify novel small molecules. However, all these methods have, in addition to advantages, also significant pitfalls. The aim of this study was to compare some commonly used computational methods to estimate their ability to separate highly active PDE4B-inhibitors from less active and inactive ones. Here, 152 molecules with pIC 50 -range of 3.4-10.5, originating from six original studies were used. High correlation coefficients by using dockin…
Effects of SCA40 on human isolated bronchus and human polymorphonuclear leukocytes: comparison with rolipram, SKF94120 and levcromakalim
1996
1. SCA40 (0.1 nM-0.1 mM) produced concentration-dependent suppression of the spontaneous tone of human isolated bronchus (-log EC50 = 6.85 +/- 0.09; n = 10) and reached a maximal relaxation similar to that of theophylline (3 mM). The potency (-log EC50 values) of SCA40 compared to other relaxants was rolipram (7.44 +/- 0.12; n = 9) > SCA40 > or = levcromakalim (6.49 +/- 0.04; n = 6) > SKF94120 (5.87 +/- 0.10; n = 9). 2. When tested against the activity of the isoenzymes of cyclic nucleotide phosphodiesterase (PDE) isolated from human bronchus, SCA40 proved highly potent against PDE III (-log IC50 = 6.47 +/- 0.16; n = 4). It was markedly less potent against PDE IV (4.82 +/- 0.18; n = 4) and …