Search results for "Thionucleotides"
showing 10 items of 17 documents
6-thioguanosine diphosphate and triphosphate levels in red blood cells and response to azathioprine therapy in Crohn's disease.
2005
Background & Aims: Azathioprine is the gold standard for immunosuppressive therapy in Crohn's disease (CD) and its molecular mechanism of action is caused by the metabolite 6-thioguanosine triphosphate (TGTP). In this study we assessed the impact of TGTP levels for monitoring of azathioprine therapy. Methods: A novel, highly sensitive assay was established to measure levels of TGTP and its precursors 6-thioguanosine monophosphates and 6-thioguanosine diphosphates (TGDP) in red blood cells from 50 CD patients. The results were correlated with clinical outcome. Results: TGTP levels could be quantified in 47 patients and a subgroup of these patients showed significantly high levels of TGDP. 6-…
Evidence for the presence of P2y and P2x receptors with different functions in mouse stomach.
2005
To clarify the function of P2 receptor subtypes in mouse stomach, the motor responses to ATP, alpha,beta-methyleneATP (alpha,beta-MeATP), P2X receptor agonist, 2-methylthioATP (2-MeSATP), P2Y receptor agonist, and the effects of the desensitisation of P2X receptors with alpha,beta-MeATP and of P2Y receptors with ADPbetaS were analysed recording the endoluminal pressure from whole-organ. ATP-induced relaxation was antagonised by suramin, non-selective P2 receptor antagonist, by desensitisation of P2Y receptors with ADPbetaS, and increased by desensitisation of P2X receptors with alpha,beta-MeATP. alpha,beta-MeATP produced biphasic responses: relaxation, reduced by P2X- or P2Y desensitisation…
Phosphorylation of carcinogen metabolizing enzymes: regulation of the phosphorylation status of the major phenobarbital inducible cytochromes P-450 i…
1989
We present data showing that the major phenobarbital inducible cytochromes P-450 (cytochrome P-450IIB1 and cytochrome P-450IIB2) were phosphorylated in intact hepatocytes. This phosphorylation was greatly increased by the cAMP derivatives N6-dibutyryl-cAMP and 8-thiomethyl-cAMP mediated by a cAMP-dependent protein kinase. Most importantly the phosphorylation status of cytochromes P-450 was shown to change in the hepatocytes after treatment with glucagon, which is known to increase the level of cAMP in hepatocytes. The observed impact of the hormone glucagon on the phosphorylation of distinct cytochrome P-450 forms in intact hepatocytes reveals the possibility that the enzyme activity of cyt…
Bcl-2 and glutathione depletion sensitizes B16 melanoma to combination therapy and eliminates metastatic disease.
2007
Abstract Purpose: Advanced melanoma resists all current therapies, and metastases in the liver are particularly problematic. Prevalent resistance factors include elevated glutathione (GSH) and increased expression of bcl-2 in melanoma cells. GSH has pleiotropic effects promoting cell growth and broad resistance to therapy, whereas Bcl-2 inhibits the activation of apoptosis and contributes to elevation of GSH. This study determined the in vivo efficacy of combination therapies administered while GSH and Bcl-2 were individually and simultaneously decreased in metastatic melanoma lesions. Experimental Design: Highly metastatic murine B16 melanoma (B16M-F10) cells have elevated levels of both G…
Pharmacokinetics of oligodeoxynucleotides encapsulated in liposomes: effect of lipid composition and preparation method
2000
1. The effect of the method employed to prepare liposomes and their lipid composition were evaluated in terms of the encapsulation efficiency and pharmacokinetic features of two oligodeoxynucleotides of a 21 mer: the normal (N-Odn) and the phosphorothioate (S-Odn) oligodeoxynucleotide. 2. Liposomes were prepared by the classical method of multilamellar vesicles (MV) and by the dehydration-rehydration method (DR). Two lipid mixtures were used to prepare liposomes--the predominant lipid being phosphatidylcholine (PC) and sphingomyelin (SM) respectively. 3. The DR method for liposome preparation provided the highest encapsulation efficiency, regardless of liposome lipid composition and the typ…
cGMP-Dependent Protein Kinase I Mediates the Negative Inotropic Effect of cGMP in the Murine Myocardium
2002
To study the role of cGMP-dependent protein kinase I (cGKI) for cardiac contractility, force of contraction (F c ) was studied in electrically driven heart muscle from wild-type (WT) mice and from conventional and conditional cGKI knockout mice. Both 8-Br-cGMP and 8-pCPT-cGMP reduced Fc in cardiac muscle from juvenile WT but not from juvenile cGKI-null mutants. Similarly, the cGMP analogues reduced F c in forskolin-stimulated ventricular muscle from WT mice but not from cGKI-null mutants. In contrast, carbachol reduced F c in both groups of animals. 8-Br-cGMP reduced F c also in heart muscle from adult WT mice but not from adult cardiomyocyte-specific cGKI-knockout mice. These results demo…
Local administration of antisense phosphorothioate oligonucleotides to the c-kit ligand, stem cell factor, suppresses airway inflammation and IL-4 pr…
2001
Abstract Background: The c-kit ligand, stem cell factor (SCF), is an important activating and chemotactic factor for both mast cells and eosinophils. These cells are known to play a fundamental role in the pathogenesis of asthma. Objective: Our goal was to analyze the functional role of SCF in the pathogenesis of asthma. Methods: The expression of SCF was targeted in fibroblasts, epithelial cells, and locally in a murine model of asthma in mice induced by ovalbumin sensitization with an antisense DNA strategy. Results: We could suppress SCF expression in NIH 3T3 fibroblasts and SP1 epithelial cells by a specific antisense phosphorothioate oligonucleotide overlapping the translation start si…
Neuroprotection elicited by P2Y13 receptors against genotoxic stress by inducing DUSP2 expression and MAPK signaling recovery.
2014
AbstractNucleotides activating P2Y13 receptors display neuroprotective actions against different apoptotic stimuli in cerebellar granule neurons. In the present study, P2Y13 neuroprotection was analyzed in conditions of genotoxic stress. Exposure to cisplatin and UV radiation induced caspase-3-dependent apoptotic cell death, and p38 MAPK signaling de-regulation. Pre-treatment with P2Y13 nucleotide agonist, 2methyl-thio-ADP (2MeSADP), restored granule neuron survival and prevented p38 long-lasting activation induced by cytotoxic treatments. Microarray gene expression analysis in 2MeSADP-stimulated cells revealed over-representation of genes related to protein phosphatase activity. Among them…
Neurotransmitters involved in the fast inhibitory junction potentials in mouse distal colon
2003
We investigated, in murine colon circular muscle, the role of adenosine 5′-triphosphate (ATP) and pituitary adenylate cyclase activating peptide (PACAP) as inhibitory neurotransmitters of the fast component of nerve-evoked inhibitory junction potential (fast IJP). Fast IJP was antagonised by apamin or suramin, abolished by desensitisation with the P2Y receptor agonist, adenosine 5′-O-2-thiodiphosphate (ADPβS), unaffected by desensitisation with P2X receptor agonist, α,β-methylene ATP (α,β-meATP), and reduced by PACAP-(6-38), a PACAP receptor antagonist. ATP induced membrane hyperpolarization resistant to tetrodotoxin, Nω-nitro-L-arginine methyl ester (L-NAME) or PACAP-(6-38), but antagonise…
Activation of P2Y receptors by ATP and by its analogue, ADPbetaS, triggers two calcium signal pathways in the longitudinal muscle of mouse distal col…
2008
Our previous research showed that ATP and adenosine 5'-O-2-thiodiphosphate (ADPbetaS) induce contractile effects in the longitudinal muscle of mouse distal colon via activation of P2Y receptors which are not P2Y(1) or P2Y(12) subtypes. This study investigated the nature of the P2Y receptor subtype(s) and the mechanisms leading to the intracellular calcium concentration increase necessary to trigger muscular contraction. Motor responses of mouse colonic longitudinal muscle to P2Y receptor agonists were examined in vitro as changes in isometric tension. ATP or ADPbetaS induced muscular contraction, which was not affected by P2Y(11) or P2Y(13) selective antagonists. Calcium-free solution or th…