Search results for " phosphodiesterase"

Structure–activity relationship of sphingomyelin analogs with sphingomyelinase from Bacillus cereus

2012

AbstractThe aim of this study was to examine how structural properties of different sphingomyelin (SM) analogs affected their substrate properties with sphingomyelinase (SMase) from Bacillus cereus. Using molecular docking and dynamics simulations (for SMase–SM complex), we then attempted to explain the relationship between SM structure and enzyme activity. With both micellar and monolayer substrates, 3O-methylated SM was found not to be degraded by the SMase. 2N-methylated SM was a substrate, but was degraded at about half the rate of its 2NH–SM control. PhytoPSM was readily hydrolyzed by the enzyme. PSM lacking one methyl in the phosphocholine head group was a good substrate, but PSM lack…

Dual effect of ceramide on human endothelial cells: induction of oxidative stress and transcriptional upregulation of endothelial nitric oxide syntha…

2002

Background— Generation of the second-messenger molecule ceramide by stimulated sphingomyelinase activity has been implicated in the inflammatory processes contributing to the pathogenesis of atherosclerosis. However, reports of stimulatory effects of ceramide on endothelial NO production in animal models suggest antiatherosclerotic effects of the molecule. Therefore, we investigated long-term effects of ceramide on NO generation in human endothelial cells. Methods and Results— In human umbilical vein endothelial cells (HUVECs) and in HUVEC-derived EA.hy 926 endothelial cells, C6-ceramide ( N -hexanoyl- d -erythro-sphingosine) reduced the generation of bioactive NO (RFL-6 reporter-cell assa…

Characterization of Membrane-Bound Cyclic Nucleotide Phosphodiesterases from Bovine Aortic Smooth Muscle

1992

This study reports the isolation and characterization of cyclic nucleotide phosphodiesterases (PDEs) associated with membrane fraction in comparison to cytosolic forms from bovine aorta. DEAE-Sephacel chromatography of a solubilized membrane fraction from a homogenate, prepared under isotonic conditions in the presence of protease inhibitors, yielded one major peak of PDE activity that specifically hydrolyzed cAMP and was not stimulated by calmodulin: It appeared to contain two subtypes of PDE. The first subtype belonged to the cyclic GMP (cGMP)-inhibited PDE family, (PDE III): It had an apparent Km value of 0.4 microM and was potently inhibited by cGMP, LY186126, and cilostamide. The secon…

Use of two-dimensional thin-layer chromatography for the components study of poly(adenosine diphosphate ribose)

1990

Two-dimensional thin-layer chromatography on cellulose plates has been used for separating and quantifying the three adenosine derivatives: AMP, phosphoribosyl AMP (PRAMP), and (PR)2AMP obtained by venom phosphodiesterase digestion of poly(ADP-ribose). In vitro synthesized polymer, up to 300 derivatives in length were studied. Some parameters of the complexity of poly(ADP-ribose) could be deduced from our results: (i) The first branching point appears in fragments of approximately 21 derivatives in length. (ii) The branching points are located at regular distances of approximately 41 derivatives from each other.

Mechanism of action of the betalain pigment indicaxanthin, purified from fruits of Opuntia ficus-indica, on mouse ileal motility in vitro.

2010

Cilostazol and atherogenic dyslipidemia: a clinically relevant effect

2011

Cilostazol is a reversible, selective inhibitor of PDE3A able to significantly improve walking distance in patients with intermittent claudication. However, beyond its antiplatelet and vasodilator properties, cilostazol seems to have significant effects on atherogenic dyslipidemia.The effects of cilostazol on plasma lipids, lipoproteins, apolipoproteins and postprandial lipemia are reviewed. A literature search (using Medline and Scopus) was performed up to 24 October 2010. The authors also manually reviewed the references of selected articles for any pertinent material.Cilostazol is able to significantly lower plasma triglyceride levels, with a concomitant increase in high-density lipoprot…

Phosphodiesterase-4 inhibition improves corticosteroid insensitivity in pulmonary endothelial cells under oxidative stress.

2012

Several clinical studies have shown that smoking in asthmatics and chronic obstructive pulmonary disease patients is closely associated with corticosteroid refractoriness. In this work, we have analyzed glucocorticoid insensitivity in human pulmonary artery endothelial cells (HPAECs) under cigarette smoke extract (CSE) exposure as well as the possible additive effects of the combination therapy with a phosphodiesterase (PDE)-4 inhibitor. Interleukin (IL)-8 was measured in cell supernatants by ELISA. Histone deacetylase (HDAC), histone acetylase (HAT), and intracellular cAMP levels were measured by colorimetric assays and enzyme immunoassay, respectively. PDE4 isotypes and glucocorticoid rec…

The phototransduction cascade in the isolated chick pineal gland revisited.

2003

It is well established that the isolated chick pineal gland is directly light sensitive and that melatonin synthesis of the gland can be inhibited by exposing the gland to light during scotophase. Since not all the steps of the phototransduction cascade have been clarified to the same extent as in the retina, we have treated isolated chick pineal glands with 90 min of light during scotophase and with drugs that affect key-components of vertebrate phototransduction, i.e., cyclic guanosine monophosphate (cGMP) phosphodiesterase 6 (PDE6), cGMP levels and cGMP-gated calcium channels. The endpoint measured was the activity of the rate-limiting enzyme of melatonin synthesis, arylalkylamine N-acet…

Nitric oxide synthases: regulation and function

2011

Nitric oxide (NO), the smallest signalling molecule known, is produced by three isoforms of NO synthase (NOS; EC 1.14.13.39). They all utilize l-arginine and molecular oxygen as substrates and require the cofactors reduced nicotinamide-adenine-dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), and (6R-)5,6,7,8-tetrahydrobiopterin (BH(4)). All NOS bind calmodulin and contain haem. Neuronal NOS (nNOS, NOS I) is constitutively expressed in central and peripheral neurons and some other cell types. Its functions include synaptic plasticity in the central nervous system (CNS), central regulation of blood pressure, smooth muscle relaxation, and vasodila…

ROLIPRAM INHIBITS PAF-INDUCED AIRWAY MICROVASCULAR LEAKAGE IN GUINEA-PIG - A COMPARISON WITH MILRINONE AND THEOPHYLLINE

1992

The effects of 3 phosphodiesterase (PDE) inhibitors, rolipram (PDE IV), milrinone (PDE III) and theophylline (non-selective) on PAF (50 ng kg-1; iv)-induced airway vascular leakage have been evaluated in guinea-pigs. Rolipram (3-300 micrograms kg-1; iv) reduced the increase in permeability induced by PAF at all airway levels whereas milrinone (10-1000 micrograms kg-1; iv) and theophylline (30 mg kg-1; iv) were without effects. The anti-leakage activity of rolipram may be of therapeutic value in asthma.