Cyclic Nucleotide Phosphodiesterases, Type 1: A CALCIUM and CALMODULIN-dependent cyclic nucleotide phosphodiesterase subfamily. The three members of this family are referred to as type 1A, type 1B, and type 1C and are each product of a distinct gene. In addition, multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing. Although the type 1 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 126.96.36.199), some members of this class have additional specificity for CYCLIC GMP.3',5'-Cyclic-AMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.Cyclic Nucleotide Phosphodiesterases, Type 4: A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. The enzyme family includes over twenty different variants that occur due to multiple ALTERNATIVE SPLICING of the mRNA of at least four different genes.Cyclic Nucleotide Phosphodiesterases, Type 3: A cyclic nucleotide phosphodiesterase subfamily that is inhibited by the binding of CYCLIC GMP to an allosteric domain found on the enzyme and through phosphorylation by regulatory kinases such as PROTEIN KINASE A and PROTEIN KINASE B. The two members of this family are referred to as type 3A, and type 3B, and are each product of a distinct gene. In addition multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing.Cyclic Nucleotide Phosphodiesterases, Type 2: A cyclic nucleotide phosphodiesterase subfamily that is activated by the binding of CYCLIC GMP to an allosteric domain found on the enzyme. Multiple enzyme variants of this subtype can be produced due to multiple alternative mRNA splicing. The subfamily is expressed in a broad variety of tissues and may play a role in mediating cross-talk between CYCLIC GMP and CYCLIC CMP pathways. Although the type 2 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 188.8.131.52), members of this class have additional specificity for CYCLIC GMP.Phosphoric Diester Hydrolases: A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 184.108.40.206',3'-Cyclic-Nucleotide Phosphodiesterases: Nucleoside-2',3'-cyclic phosphate nucleotidohydrolase. Enzymes that catalyze the hydrolysis of the 2'- or 3'- phosphate bonds of 2',3'-cyclic nucleotides. Also hydrolyzes nucleoside monophosphates. Includes EC 220.127.116.11 and EC 18.104.22.168. EC 3.1.4.-.Nucleotides, CyclicPhosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.3',5'-Cyclic-GMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.Cyclic Nucleotide Phosphodiesterases, Type 5: A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in vascular tissue and plays an important role in regulating VASCULAR SMOOTH MUSCLE contraction.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Cyclic Nucleotide Phosphodiesterases, Type 7: A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC AMP. Several isoforms of the enzyme type exist, each with its own tissue localization. The isoforms are encoded by at least two genes and are a product of multiple alternative splicing of their mRNAs.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Rolipram: A phosphodiesterase 4 inhibitor with antidepressant properties.1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASESPurinonesIsoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Kinetics: The rate dynamics in chemical or physical systems.Cyclic Nucleotide Phosphodiesterases, Type 6: A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in the outer segment PHOTORECEPTOR CELLS of the RETINA. It is comprised of two catalytic subunits, referred to as alpha and beta, that form a dimer. In addition two regulatory subunits, referred to as gamma and delta, modulate the activity and localization of the enzyme.Nucleotides: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)Phosphodiesterase 3 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 3.Phosphodiesterase 4 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 4.4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone: Inhibitor of phosphodiesterases.Dibutyryl Cyclic GMP: N-(1-Oxobutyl)-cyclic 3',5'-(hydrogen phosphate)-2'-butanoate guanosine. A derivative of cyclic GMP. It has a higher resistance to extracellular and intracellular phosphodiesterase than cyclic GMP.Theophylline: A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.Phosphodiesterase I: A phosphoric diester hydrolase that removes 5'-nucleotides from the 3'-hydroxy termini of 3'-hydroxy-terminated OLIGONUCLEOTIDES. It has low activity towards POLYNUCLEOTIDES and the presence of 3'-phosphate terminus on the substrate may inhibit hydrolysis.Cyclic Nucleotide-Gated Cation Channels: A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.Phosphorus-Oxygen Lyases: Enzymes that catalyze the cleavage of a phosphorus-oxygen bond by means other than hydrolysis or oxidation. EC 4.6.Milrinone: A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase type 3 activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the inotropic potency of amrinone.Bucladesine: A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)Pyrrolidinones: A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)Adenine NucleotidesCyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 22.214.171.124.Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.Cyclic IMP: Inosine cyclic 3',5'-(hydrogen phosphate). An inosine nucleotide which acts as a mild inhibitor of the hydrolysis of cyclic AMP and cyclic GMP and as an inhibitor of cat heart cyclic AMP phosphodiesterase.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 126.96.36.199.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Phosphodiesterase 5 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 5.8-Bromo Cyclic Adenosine Monophosphate: A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Guanine NucleotidesCattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Xanthines: Purine bases found in body tissues and fluids and in some plants.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Vinca Alkaloids: A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.Cyclic P-OxidesEnzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Cloning and characterization of PDE7B, a cAMP-specific phosphodiesterase. (1/27)A member of the phosphodiesterase (PDE)7 family with high affinity and specificity for cAMP has been identified. Based on sequence homologies, we designate this PDE as PDE7B. The full-length cDNA of PDE7B is 2399 bp, and its ORF sequence predicts a protein of 446 amino acids with a molecular mass of 50.1 kDa. Comparison of the predicted protein sequences of PDE7A and PDE7B reveals an identity of 70% in the catalytic domain. Northern blotting indicates that the mRNA of PDE7B is 5.6 kb. It is most highly expressed in pancreas followed by brain, heart, thyroid, skeletal muscle, eye, ovary, submaxillary gland, epididymus, and liver. Recombinant PDE7B protein expressed in a Baculovirus expression system is specific for cAMP with a K(m) of 0.03 microM. Within a series of common PDE inhibitors, it is most potently inhibited by 3-isobutyl-1-methylxanthine with an IC(50) of 2.1 microM. It is also inhibited by papaverine, dipyridamole, and SCH51866 at higher doses. PDE7A and PDE7B exhibit the same general pattern of inhibitor specificity among the several drugs tested. However, differences in IC(50) for some of the drugs suggest that isozyme selective inhibitors can be developed. (+info)
Novel alternative splice variants of rat phosphodiesterase 7B showing unique tissue-specific expression and phosphorylation. (2/27)cDNA species coding for novel variants of cyclic-AMP-specific phosphodiesterases (PDEs), namely the PDE7B family, were isolated from rats and characterized. Rat PDE7B1 (RNPDE7B1) was composed of 446 amino acid residues. Rat PDE7B2 (RNPDE7B2) and PDE7B3 (RNPDE7B3), which possessed unique N-terminal sequences, consisted of 359 and 459 residues respectively. Northern hybridization analysis showed that rat PDE7B transcripts were particularly abundant in the striatum and testis. PCR analyses revealed that rat PDE7B2 transcripts were restricted to the testis and that low levels of PDE7B3 transcripts were expressed in the heart, lung and skeletal muscle. In situ hybridization analysis demonstrated that rat PDE7B transcripts were expressed in striatal neurons and spermatocytes. In spermatocytes, rat PDE7B transcripts were expressed in a stage-specific manner during spermatogenesis. The K(m) values of recombinant rat PDE7B1, PDE7B2 and PDE7B3 for cAMP were 0.05, 0.07 and 0.05 microM respectively. Each rat PDE7B variant was the most sensitive to 3-isobutyl-1-methylxanthine (IC(50) 1.5-2.1 microM). Two phosphorylation sites for cAMP-dependent protein kinase (PKA) were found in rat PDE7B1 and PDE7B3, whereas rat PDE7B2 possessed one site. PKA-dependent phosphorylation was observed in C-terminal phosphorylation sites of three rat PDE7B variants, in addition to unique N-terminal regions of rat PDE7B1 and PDE7B3. Unique tissue distribution and PKA-dependent phosphorylation of PDE7B variants suggested that each variant has a specific role for cellular functions via cAMP signalling in various tissues. (+info)
Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia. (3/27)PURPOSE: cAMP phosphodiesterase (PDE) 4 is a family of enzymes the inhibition of which induces chronic lymphocytic leukemia (CLL) apoptosis. However, leukemic cells from a subset of CLL patients are relatively resistant to treatment with the PDE4 inhibitor rolipram, particularly when this drug is used in the absence of an adenylate cyclase stimulus such as forskolin. Elevated cAMP levels induce compensatory up-regulation of several cyclic nucleotide PDE families in other model systems. We here examine the hypothesis that CLL cells that survive treatment with rolipram do so as a result of residual PDE activity that is not inhibited by this drug. EXPERIMENTAL DESIGN: We examined by Western analysis the effect of rolipram treatment on CLL expression of PDE3B, PDE4A, PDE4B, PDE4D, and PDE7A. We also examined the ability of rolipram (PDE4 inhibitor) or cilostamide (PDE3 inhibitor), alone or together, to induce apoptosis or elevate cyclic AMP in leukemic cells from patients with CLL. RESULTS: Rolipram increased levels of PDE4B and, to a variable extent, PDE4D. When combined with forskolin, rolipram also increased levels of a second family of PDEs, PDE3B. Addition of the specific PDE3 inhibitor, cilostamide, modestly augmented rolipram-induced apoptosis in five of seven "rolipram-resistant" CLL samples. CONCLUSIONS: Although this work confirms that PDE4 appears to be the most important PDE target for induction of apoptosis in CLL, combination therapy with PDE3 and PDE4 inhibitors or use of dual-selective drugs may be of benefit in a subset of relatively PDE4-inhibitor resistant CLL patients. (+info)
Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors. (4/27)Even though the existence of phosphodiesterase (PDE) 7 in T cells has been proved, the lack of a selective PDE7 inhibitor has confounded an accurate assessment of PDE7 function in such cells. In order to elucidate the role of PDE7 in human T cell function, the effects of two PDE inhibitors on PDE7A activity, cytokine synthesis, proliferation and CD25 expression of human peripheral blood mononuclear cells (PBMC) were determined. Recombinant human PDE7A was obtained and subjected to cyclic AMP-hydrolysis assay. PBMC of Dermatophagoides farinae mite extract (Df)-sensitive donors were stimulated with the relevant antigen or an anti-CD3 monoclonal antibody (MoAb). PBMC produced IL-5 and proliferated in response to stimulation with Df, while stimulation with anti-CD3 MoAb induced CD25 expression and messenger RNA (mRNA) synthesis of IL-2, IL-4 and IL-5 in peripheral T cells. A PDE inhibitor, T-2585, which suppressed PDE4 isoenzyme with high potency (IC50 = 0.00013 microM) and PDE7A with low potency (IC50 = 1.7 microM) inhibited cytokine synthesis, proliferation and CD25 expression in the dose range at which the drug suppressed PDE7A activity. A potent selective inhibitor of PDE4 (IC50 = 0.00031 microM), RP 73401, which did not effectively suppress PDE7A (IC50 > 10 microM), inhibited the Df- and anti-CD3 MoAb-stimulated responses only weakly, even at 10 microM. PDE7 may play a critical role in the regulation of human T cell function, and thereby selective PDE7 inhibitors have the potential to be used to treat immunological and inflammatory disorders. (+info)
Ubiquitous expression of phosphodiesterase 7A in human proinflammatory and immune cells. (5/27)We have determined the expression of phosphodiesterase (PDE) 7A1 and PDE7A2 in human cells that have been implicated in the pathogenesis of chronic obstructive pulmonary disease and asthma. Messenger RNA transcripts were detected by RT-PCR in T lymphocytes, monocytes, neutrophils, airway and vascular smooth muscle cells, lung fibroblasts, epithelial cells, and cardiac myocytes. Human epithelial, T cell, eosinophil, and lung fibroblast cell lines were also positive for PDE7A1 and PDE7A2 mRNA transcripts. By Western immunoblot analyses the amount of PDE7A1 was greatest in T cell lines, peripheral blood T lymphocytes, epithelial cell lines, airway and vascular smooth muscle cells, lung fibroblasts, and eosinophils but was not detected in neutrophils. In contrast, PDE7A2 protein, which was identified in human cardiac myocytes, was not found in any of the other cell types investigated. Immunoconfocal analyses showed that PDE7A was expressed in neutrophils and alveolar macrophages. As the expression of PDE7A mirrors the distribution of PDE4 we speculate that this enzyme could be a target for novel anti-inflammatory drugs. (+info)
Functional characterization of the human phosphodiesterase 7A1 promoter. (6/27)In this paper, the human phosphodiesterase 7A1 (h PDE7A1 ) promoter region was identified and functionally characterized. Transient transfection experiments indicated that a 2.9 kb fragment of the h PDE7A1 5'-flanking region, to position -2907, has strong promoter activity in Jurkat T-cells. Deletion analysis showed that the proximal region, up to position -988, contains major cis -regulatory elements of the h PDE7A1 promoter. This minimal promoter region contains a regulatory CpG island which is essential for promoter activity. The CpG island contains three potential cAMP-response-element-binding protein (CREB)-binding sites that, as judged by in vivo dimethyl sulphate (DMS) footprinting, are occupied in Jurkat T-cells. Moreover, over-expression of CREB results in increased promoter activity, but, on the other hand, promoter activity decreases when a dominant-negative form of CREB (KCREB) is over-expressed. In vivo DMS footprinting strongly indicates that other transcription factors, such Ets-2, nuclear factor of activated T-cells 1 (NFAT-1) and nuclear factor kappaB (NF-kappaB), might also contribute to the regulation of h PDE7A1 promoter. Finally, h PDE7A1 promoter was found to be induced by treatment with PMA, but not by treatment with dibutyryl cAMP or forskolin. These results provide insights into the factors and mechanisms that regulate expression of the h PDE7A gene. (+info)
Phosphodiesterase 7A-deficient mice have functional T cells. (7/27)Phosphodiesterases (PDEs) are enzymes which hydrolyze the cyclic nucleotide second messengers, cAMP and cGMP. In leukocytes, PDEs are responsible for depletion of cAMP which broadly suppresses cell functions and cellular responses to many activation stimuli. PDE7A has been proposed to be essential for T lymphocyte activation based on its induction during cell activation and the suppression of proliferation and IL-2 production observed following inhibition of PDE7A expression using a PDE7A antisense oligonucleotide. These observations have led to the suggestion that selective PDE7 inhibitors could be useful in the treatment of T cell-mediated autoimmune diseases. In the present report, we have used targeted gene disruption to examine the role PDE7A plays in T cell activation. In our studies, PDE7A knockout mice (PDE7A(-/-)) showed no deficiencies in T cell proliferation or Th1- and Th2-cytokine production driven by CD3 and CD28 costimulation. Unexpectedly, the Ab response to the T cell-dependent Ag, keyhole limpet hemocyanin, in the PDE7A(-/-) mice was found to be significantly elevated. The results from our studies strongly support the notion that PDE7A is not essential for T cell activation. (+info)
Genome annotation of a 1.5 Mb region of human chromosome 6q23 encompassing a quantitative trait locus for fetal hemoglobin expression in adults. (8/27)BACKGROUND: Heterocellular hereditary persistence of fetal hemoglobin (HPFH) is a common multifactorial trait characterized by a modest increase of fetal hemoglobin levels in adults. We previously localized a Quantitative Trait Locus for HPFH in an extensive Asian-Indian kindred to chromosome 6q23. As part of the strategy of positional cloning and a means towards identification of the specific genetic alteration in this family, a thorough annotation of the candidate interval based on a strategy of in silico / wet biology approach with comparative genomics was conducted. RESULTS: The ~1.5 Mb candidate region was shown to contain five protein-coding genes. We discovered a very large uncharacterized gene containing WD40 and SH3 domains (AHI1), and extended the annotation of four previously characterized genes (MYB, ALDH8A1, HBS1L and PDE7B). We also identified several genes that do not appear to be protein coding, and generated 17 kb of novel transcript sequence data from re-sequencing 97 EST clones. CONCLUSION: Detailed and thorough annotation of this 1.5 Mb interval in 6q confirms a high level of aberrant transcripts in testicular tissue. The candidate interval was shown to exhibit an extraordinary level of alternate splicing - 19 transcripts were identified for the 5 protein coding genes, but it appears that a significant portion (14/19) of these alternate transcripts did not have an open reading frame, hence their functional role is questionable. These transcripts may result from aberrant rather than regulated splicing. (+info)
2003). "Comparison of enzymatic characterization and gene organization of cyclic nucleotide phosphodiesterase 8 family in ... 2003). "Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer's disease brains examined by in situ ... cyclic nucleotide phosphodiesterase". Biochem Biophys Res Commun. 250 (3): 751-6. doi:10.1006/bbrc.1998.9379. PMID 9784418. " ... High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B is an enzyme that in humans is encoded by ...
"Isozyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythro-9-(2-hydroxy-3-nonyl) adenine ... which also acts as a phosphodiesterase inhibitor that selectively inhibits phosphodiesterase type 2 (PDE2). "Sigma Aldrich". ... adenine inhibits cyclic GMP-stimulated phosphodiesterase in isolated cardiac myocytes". Mol Pharmacol. 48 (1): 121-130. PMID ... 7 (7): 733-8. doi:10.1016/0898-6568(95)00042-N. PMID 8519602. Méry, PF; Pavoine, C; Pecker, F; Fischmeister, R (1995). "Erythro ...
Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". J. Allergy Clin. Immunol. 108 (5): 671-80. doi:10.1067/mai. ... Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects". J. Biol. Chem. 281 (20): 14192-206. doi: ... "Binding and Functional Comparisons of Two Types of Tumor Necrosis Factor Antagonists". Journal of Pharmacology and Experimental ... 12 (6-7): 445-52. doi:10.1016/j.phymed.2003.12.011. PMID 16008121. Raduner S, Majewska A, Chen JZ, Xie XQ, Hamon J, Faller B, ...
Discovery and development of phosphodiesterase 5 inhibitors
Lugnier, C. (2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific ... Yu, J. Y.; Kang, K. K. & Yoo, M. (2006). "Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet- ... McMahon, C. G.; McMahon, C. N.; Leow, L. J. & Winestock, C. G. (2006). "Efficacy of type-5 phosphodiesterase inhibitors in the ... Ravipati, G.; McClung, J. A.; Aronow, W. S.; Peterson, S. J.; Frishman, W. H. (2007). "Type 5 phosphodiesterase inhibitors in ...
2007). "Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes". J. Biol. Chem. 282 (45): 32749-57. doi:10.1074/ ... 2006). "Subcellular localization and regulation of type-1C and type-5 phosphodiesterases". Biochem. Biophys. Res. Commun. 341 ( ... Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C is an enzyme that in humans is encoded by the PDE1C ... Rybalkin SD, Rybalkina I, Beavo JA, Bornfeldt KE (2002). "Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth ...
"Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase". The Journal ... These proteins degrade the second messenger cAMP, which is a key signal transduction molecule in multiple cell types, including ... "Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase". The Journal ... cAMP-specific 3',5'-cyclic phosphodiesterase 4D is an enzyme that in humans is encoded by the PDE4D gene. The PDE4D gene is ...
Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are ... Sildenafil (Viagra) is an inhibitor of cGMP-specific phosphodiesterase type 5, which enhances the vasodilatory effects of cGMP ... "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Advances in Cyclic ... as well as numerous less-well-characterized small-molecule phosphodiesterases. The cyclic nucleotide phosphodiesterases ...
The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE ... "Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication" ( ... Zhou L, Thompson WJ, Potter DE (Jul 1999). "Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells" ( ... of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1)". Cellular Signalling. 6 (7): 793-812. doi ...
Modulates the activity of membrane-bound enzymes: phosphodiesterase, cyclic nucleotides, adenylate cyclase, aldoreductase, ... Its chemical structure resembles that of pyridoxine (a type of vitamin B6). It is not approved for any medical use in the ...
In mammals, GAF domains are found in five members of the cyclic nucleotide phosphodiesterase superfamily: PDE2, PDE5, and PDE6 ... The GAF domain is a type of protein domain that is found in a wide range of proteins from all species. The GAF domain is named ... The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding. Proc. Natl. Acad. Sci. U.S ... Structure of the GAF domain, a ubiquitous signaling motif and a new class of cyclic GMP receptor. EMBO J.. 2000;19(20):5288-99 ...
2',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNPase) (Ragheb 1999, p. 14). Pérez-Cerdá, Fernando; Sánchez-Gómez, María ... They are the last cell type to be generated in the CNS. Oligodendroglia, types of glial cells, arise during development from ... Oligodendrocytes (from Greek, meaning cells with a few branches), or oligodendroglia, are a type of neuroglia discovered by Pío ... "Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into ...
This G protein subunit activates a taste phosphodiesterase and decreases cyclic nucleotide levels. Further steps in the ... taste receptors, type 1 at the US National Library of Medicine Medical Subject Headings (MeSH) taste receptors, type 2 at the ... HCN1 and HCN4 (HCN channels) were two such proposals; both of these receptors are cyclic nucleotide-gated channels. The two ion ... The fourth type - filiform papillae do not contain taste buds). Beyond the papillae, taste receptors are also in the palate and ...
1998). "Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3: ... "Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential ... High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A is an enzyme that in humans is encoded by the PDE9A gene. The ... "Entrez Gene: PDE9A phosphodiesterase 9A". Verhoest PR, Fonseca KR, Hou X, et al. (2012). "Design and discovery of 6-[(3S,4S)-4- ...
This export contributes to the degradation of phosphodiesterases and possibly an elimination pathway for cyclic nucleotides. ... "cDNA cloning of a short type of multidrug resistance protein homologue, SMRP, from a human lung cancer cell line". Biochemical ... This protein functions in the cellular export of its substrate, cyclic nucleotides. ... a transporter for cyclic nucleotides, in human placenta and cultured human trophoblasts: effects of gestational age and ...
"Positive inotropic effect of the inhibition of cyclic GMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE2) on guinea ... As different PDE types may affect different cAMP pools, the different PDEs may regulate different processes in the cell. PDE2 ... "Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic Nucleotide ... June 1997). "cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes ...
Lugnier C (March 2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific ... PDE1 (phosphodiesterase type 1) is a phosphodiesterase enzyme also known as calcium- and calmodulin-dependent phosphodiesterase ... Kakkar R, Raju RV, Sharma RK (July 1999). "Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1)". Cell. Mol. Life ... Dousa TP (January 1999). "Cyclic-3',5'-nucleotide phosphodiesterase isozymes in cell biology and pathophysiology of the kidney ...
This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic ... The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a ... "Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication". ... cAMP-specific 3',5'-cyclic phosphodiesterase 4B is an enzyme that in humans is encoded by the PDE4B gene. ...
Cyclic GMP possibly opens cyclic nucleotide-gated (CNG) K+-selective channels, thereby causing hyperpolarization of the ... Kong, N., Xu, X., Zhang, Y., Wang, Y., Hao, X., Zhao, Y., Qiao, J., Xia, G. and Zhang, M. (2017) Natriuretic peptide type C ... The cGMP signal is terminated by the hydrolysis of cGMP through phosphodiesterase (PDE) activity and inactivation of GC. On ... The consequential hyperpolarization activates hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. The ...
Heterotrimeric G protein
The GTP form of the α subunit of transducin (Gt) activates the cyclic GMP phosphodiesterase from retinal rod outer segments, ... Fung, BKK; Hurley, JB; Stryer, L (1981). "Flow of information in the light-triggered cyclic nucleotide cascade of vision". Proc ... They can also activate L-type calcium channels, as in H3 receptor pharmacology. Hurowitz EH, Melnyk JM, Chen YJ, Kouros-Mehr H ... The pure beta-adrenergic receptor and guanine nucleotide regulatory protein confer hormone responsiveness on the resolved ...
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded ... Journal of Cyclic Nucleotide Research. 2 (3): 139-48. PMID 6493. Keeler, CE (20 March 1928). "The Geotropic Reaction of Rodless ... There are two types of photoreceptors: cones and rods. The rod and cone PDE6 complexes have different structures. PDE6β ... Organization of the gene for the beta-subunit of human photoreceptor cyclic GMP phosphodiesterase]". Bioorganicheskaia Khimiia ...
List of EC numbers (EC 3)
... cyclic-nucleotide 2'-phosphodiesterase EC 188.8.131.52: 3',5'-cyclic-nucleotide phosphodiesterase EC 184.108.40.206: now EC 220.127.116.11 EC ... type I site-specific deoxyribonuclease EC 18.104.22.168: type II site-specific deoxyribonuclease EC 22.214.171.124: type III site-specific ... cyclic-GMP phosphodiesterase EC 126.96.36.199: now with EC 188.8.131.52 EC 184.108.40.206: 2',3'-cyclic-nucleotide 3'-phosphodiesterase EC 3.1 ... cyclic-guanylate-specific phosphodiesterase EC 220.127.116.11: 3',5'-cyclic-AMP phosphodiesterase EC 18.104.22.168: N- ...
Myelin basic protein
Cyclic-nucleotide 3'-phosphodiesterase and multiple molecules of the Immune system. GRCh38: Ensembl release 89: ENSG00000197971 ... In general, the major form of MBP is a protein of about 18.5 Kd (170 residues). In melanocytic cell types, MBP gene expression ... 35 (7): 503-542. doi:10.1016/j.micron.2004.04.005. Boylan KB, Ayres TM, Popko B, et al. (1990). "Repetitive DNA (TGGA)n 5' to ... 264 (9): 5121-7. PMID 2466844. Edwards AM, Ross NW, Ulmer JB, Braun PE (1989). "Interaction of myelin basic protein and ...
"Functional and biochemical evidence for diazepam as a cyclic nucleotide phosphodiesterase type 4 inhibitor" (pdf). British ... A phosphodiesterase type 4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action ... Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E (1998). "Rolipram, a type IV-specific phosphodiesterase inhibitor, ... Dinter, H (February 2000). "Phosphodiesterase type 4 inhibitors: potential in the treatment of multiple sclerosis?". BioDrugs. ...
2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): 671-80. doi:10.1067/mai ... Jan 2012). "Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental ... Fertel, R. and Weiss, B.: Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung" Mol. ... Weiss B (1975). "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Adv. ...
Pharmacology of antidepressants
... by adenylyl cyclase and metabolized by cyclic nucleotide phosphodiesterases (PDEs). One manifestation of depression is an ... a type of glutamate receptor - produces rapid (within 2 hours), robust and sustained (lasting for up to a fortnight) ... Rodent studies have consistently shown upregulation of the 3, 5-cyclic adenosine monophosphate (cAMP) system induced by ... "Interaction between the antidepressant-like behavioral effects of beta adrenergic agonists and the cyclic AMP PDE inhibitor ...
This compound is a potent inhibitor of cGMP specific phosphodiesterase type 5, the enzyme that degrades the signalling molecule ... This block of nucleotide biosynthesis is more toxic to rapidly growing cells than non-dividing cells, since a rapidly growing ... cyclic guanosine monophosphate. This signalling molecule triggers smooth muscle relaxation and allows blood flow into the ... Although it is possible for mixed-type inhibitors to bind in the active site, this type of inhibition generally results from an ...
A new study looking at cosmic dust that fell on Earth billions of years ago shows that the planets ancient atmosphere was a lot different than we thought.
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But as I consider our Gospel reading today, where our Lord tells us he is the gate of the sheepfold, meaning that he is the right way for all to enter into the kingdom of God, I can not help thinking of how we are all called to be as Christ-like as possible; meaning that we must follow the example of Christ in helping others find the path to their salvation. What great benefit it would be to the salvation of souls if we encouraged others to stay on the right path, calling them back when they go wrong, tempted off course by what looks like an easier path, when the true path begins to look tough. And what benefit to us if others would help us also in a similar fashion, calling out to us. whenever we meet Buen Camino, meaning not that rocky road in Spain, but the Way that Christ laid before us. In such a way they would be as angels to us - even as we could be as angels to them. My prayer as I end is that all here will do their best to be as angels to all they meet, doing their best to guide them ...
Click here for your special deal on Vinpocetine…<...
Hagiwara M, Endo T, Hidaka H Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle . Biochem ... show that Vinpocetine, a phosphodiesterase (PDE) inhibitor known for its minimal side effects and great potential in cognitive ... Solntseva EI, Bukanova JV, Skrebitsky VG The nootropic drug vinpocetine modulates different types of potassium currents in ... Chiu PJ, et al Comparative effects of vinpocetine and 8-Br-cyclic GMP on the contraction and 45Ca-fluxes in the rabbit aorta . ...http://www.targetednutrients.com/vinpocetine/
A Genome-Wide Scan for Common Variants Affecting the Rate of Age-Related Cognitive Decline - PubMed
Cyclic Nucleotide Phosphodiesterases, Type 7 / genetics Actions. * Search in PubMed * Search in MeSH ... Using aggregate measures of genetic risk, we find that known susceptibility loci for cardiovascular disease, type 2 diabetes, ... 2013 Sep 1;70(9):1150-7. doi: 10.1001/jamaneurol.2013.2815. JAMA Neurol. 2013. PMID: 23836404 Free PMC article. ... 2019 May 7;10(5):341. doi: 10.3390/genes10050341. Genes (Basel). 2019. PMID: 31067744 Free PMC article. ...https://phgkb.cdc.gov/PHGKB/phgHome.action?action=forward&dbsource=huge&id=67659
3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily (IPR036971) | InterPro | EMBL-EBI
Type 3 phosphodiesterase inhibitors may be protective against cerebrovascular events in patients with claudication.. null 17 ... The cyclic nucleotide phosphodiesterases (PDE) comprise a group of enzymes that degrade the phosphodiester bond in the second ... 35-cyclic nucleotide phosphodiesterase, catalytic domain superfamily (IPR036971). Short name: PDEase_catalytic_dom_sf ... They regulate the localisation, duration and amplitude of cyclic nucleotide signalling within subcellular domains. PDEs are ...http://www.ebi.ac.uk/interpro/entry/IPR036971
DIGITAL.CSIC: Phosphodiesterase 7 inhibition preserves dopaminergic neurons in cellular and rodent models of Parkinson disease
Cyclic-nucleotide phosphodiesterases. Nonsteroidal antiinflammatory drugs. Neuroblastoma sh-sy5y cells. Binding-protein-beta. ... This cyclic nucleotide plays a key role in signal transduction in a wide variety of cellular responses. In the brain, cAMP has ... Background]: Phosphodiesterase 7 plays a major role in down-regulation of protein kinase A activity by hydrolyzing cAMP in many ... cell types. ... Here we show a novel function of phosphodiesterase 7 inhibition ...https://digital.csic.es/handle/10261/39715
JoVE Search Results: Cyclic Nucleotide Phosphodiesterases%2C Type 5
The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis. Abstract Baillie, George S. University of Glasgow ... Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. Abstract Parent, Carole A. ... Cyclic nucleotide compartmentalization: contributions of phosphodiesterases and ATP-binding cassette transporters. Abstract ... Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation. Abstract ...http://labindex.jove.com/group/Cyclic-Nucleotide-Phosphodiesterases%2C-Type-5
Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin...
... cyclic AMP, cyclic nucleotide phosphodiesterases, type 1, glucose, humans, insulin, insulin-like growth factor I, islets of ... Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin ... Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin ... 1. The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN - BD11, were characterized ...https://strathprints.strath.ac.uk/34954/
IL12B | Cancer Genetics Web
... cyclic-nucleotide phosphodiesterase). Enriched pathways include hsa04512 (ECM-receptor interaction), hsa04510 (Focal adhesion ... Type I diabetes mellitus KEGG. Data from KEGG and BioCarta [BIOCARTA terms] via CGAP [Hide] ... Nucleotide variation in IL-10 and IL-12 and their receptors and cervical and vulvar cancer risk: a hybrid case-parent triad and ... T-helper 1 type immune response - T-helper cell differentiation Data from Gene Ontology via CGAP [Hide] ...http://www.cancerindex.org/geneweb/IL12B.htm
LRP1B | Cancer Genetics Web
... cyclic-nucleotide phosphodiesterase). Enriched pathways include hsa04512 (ECM-receptor interaction), hsa04510 (Focal adhesion ... These two types of alterations occurring in multiple large CFS genes may contribute significantly to the heterogeneity observed ... Our results indicate that adult WT is a biological entity distinct from the corresponding pediatric tumor type.. Related: ... We here present the first published high-resolution genomic analysis of a mixed-type adult WT. This revealed a more pronounced ...http://www.cancerindex.org/geneweb/LRP1B.htm
PDE8B - Wikipedia
2003). "Comparison of enzymatic characterization and gene organization of cyclic nucleotide phosphodiesterase 8 family in ... 2003). "Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimers disease brains examined by in situ ... cyclic nucleotide phosphodiesterase". Biochem Biophys Res Commun. 250 (3): 751-6. doi:10.1006/bbrc.1998.9379. PMID 9784418. " ... High affinity cAMP-specific and IBMX-insensitive 3,5-cyclic phosphodiesterase 8B is an enzyme that in humans is encoded by ...https://en.wikipedia.org/wiki/PDE8B
EHNA - Wikipedia
"Isozyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythro-9-(2-hydroxy-3-nonyl) adenine ... which also acts as a phosphodiesterase inhibitor that selectively inhibits phosphodiesterase type 2 (PDE2). "Sigma Aldrich". ... adenine inhibits cyclic GMP-stimulated phosphodiesterase in isolated cardiac myocytes". Mol Pharmacol. 48 (1): 121-130. PMID ... 7 (7): 733-8. doi:10.1016/0898-6568(95)00042-N. PMID 8519602. Méry, PF; Pavoine, C; Pecker, F; Fischmeister, R (1995). "Erythro ...https://en.wikipedia.org/wiki/EHNA
JCI - Phosphodiesterase 4B in the cardiac L-type Ca2+ channel complex regulates Ca2+ current and protects against ventricular...
Compartmentation of cyclic nucleotide signaling in the heart: The role of cyclic nucleotide phosphodiesterases. Circ Res. 2006; ... Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L-type Ca2+ current in ... Cyclic Nucleotide Phosphodiesterases in Health and Disease . Florence, Kentucky, USA: CRC Press, Taylor and Francis Group; 2007 ... Richter W, Jin SL, Conti M. Splice variants of the cyclic nucleotide phosphodiesterase PDE4D are differentially expressed and ...https://9iyoo.org.mobile.jci.org/articles/view/44747
Type 5 Cyclic Nucleotide Phosphodiesterases Transient Receptor Potential Channels Calcineurin Pulmonary Artery ... Inhibition of phosphodiesterase-5 suppresses calcineurin/NFAT-mediated TRPC6 expression in pulmonary artery smooth muscle cells ... Liu, Q., Li, D., Berger, A. E., Johns, R. A. & Gao, L. Dec 1 2017 In : Scientific Reports. 7, 1, 11957. Research output: ... 36-42 7 p.. Research output: Research - peer-review › Article ... Single Nucleotide Polymorphism Medicine & Life Sciences Acute ...https://jhu.pure.elsevier.com/en/persons/li-gao
Phosphodiesterase 4-targeted treatments for autoimmune diseases | BMC Medicine | Full Text
... a specific cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitor. PLoS One. 2012, 7: e28899-10.1371/journal.pone.0028899. ... The flavonoid dioclein is a selective inhibitor of cyclic nucleotide phosphodiesterase type 1 (PDE1) and a cGMP-dependent ... Essayan DM: Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation. Biochem Pharmacol. 1999, 57: 965-973. ... Brideau C, Van Staden C, Styhler A, Rodger IW, Chan CC: The effects of phosphodiesterase type 4 inhibitors on tumour necrosis ...https://0-bmcmedicine-biomedcentral-com.brum.beds.ac.uk/articles/10.1186/1741-7015-11-96
uBibliorum: cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes
To investigate the role of PDE2 in the regulation of cardiac L-type Ca2+ current (ICa), we have examined the effect of EHNA on ... cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes. ... Both PDE2 and PDE3 may contribute to keep the cyclic nucleotides concentrations at minimum in the absence of adenylyl and/or ... Recently, EHNA was shown to block the activity of purified soluble cGMPstimulated phosphodiesterase (PDE2) from frog, human, ...https://ubibliorum.ubi.pt/handle/10400.6/549
Fine mapping of AHI1 as a schizophrenia susceptibility gene: from association to evolutionary evidence. - PubMed - NCBI
Cyclic Nucleotide Phosphodiesterases, Type 7/genetics. *Genetic Association Studies*. *Genetic Predisposition to Disease* ... Publication type, MeSH terms, Substances. Publication type. *Research Support, Non-U.S. Govt ... Our strongest findings lay within the AHI1 gene: single-nucleotide polymorphisms rs11154801 and rs7759971 showed significant ...https://phgkb.cdc.gov/PHGKB/phgHome.action?action=forward&dbsource=huge&id=52252
Rapid nitric oxide-induced desensitization of the cGMP response is caused by increased activity of phosphodiesterase type 5...
Cyclic GMP as substrate and regulator of cyclic nucleotide phosphodiesterases (PDEs). Rev. Physiol. Biochem. Pharmacol. 135:67- ... Concentration and regulation of cyclic nucleotides, cyclic-nucleotide-dependent protein kinases and one of their major ... Cyclic nucleotide phosphodiesterases: relating structure and function. Prog. Nucleic Acid. Res. Mol. Biol. 65:1-52. ... Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP- ...http://jcb.rupress.org/content/155/2/271
Search Articles | University of Toronto Libraries
Cyclic Nucleotide Phosphodiesterases, Type 7 - genetics , Protein Tyrosine Phosphatases, Non-Receptor - genetics , Adult , ... Background: We investigated phosphodiesterase 7B (PDE7B), neuromedin B receptor (NMBR) and epilepsy progressive myoclonus type ... Cyclic AMP Response Element-Binding Protein - genetics , Psychiatric Status Rating Scales , Cyclic AMP Response Element ... Psychiatry , Major depression , Bipolar disorder , Single nucleotide polymorphisms , PROTEIN , PSYCHIATRY , SCHIZOPHRENIA , ...https://query.library.utoronto.ca/index.php/search/q?kw=Author:Balzarro,%20Beatrice
Search Articles | University of Toronto Libraries
Cyclic Nucleotide Phosphodiesterases, Type 7 - antagonists & inhibitors , Schizophrenia - drug therapy , Neural Inhibition - ... PHOSPHODIESTERASE INHIBITORS , CYCLIC-AMP , MOUSE MODEL , PHARMACOLOGY & PHARMACY , LONG-TERM POTENTIATION , MOOD STABILIZERS ... Phosphodiesterase Inhibitors - administration & dosage , Animals , Nootropic Agents - administration & dosage , Quinazolines - ... Memory - drug effects , Phosphodiesterase Inhibitors - therapeutic use , Triazoles - administration & dosage , Drugs, ...https://query.library.utoronto.ca/index.php/search/q?kw=SubjectTerms:Cognition%20enhancer
Phosphodiesterase 4B is essential for lipopolysaccharide-induced CC chemokine ligand 3 production in mouse macrophages.( ... Original Article, Report) by Journal of Medical Sciences; Health, general Gel electrophoresis Analysis Phosphodiesterases ... Biochemistry and physiology of cyclic nucleotide phosphodiesterases: Essential components in cyclic nucleotide signaling. Annu ... Regulation of distinct cyclic AMP-specific phosphodiesterase (phosphodiesterase type 4) isozymes in human monocytic cells. Mol ...https://www.thefreelibrary.com/Phosphodiesterase+4B+is+essential+for+lipopolysaccharide-induced+CC...-a0419362282
Effect of icariin on cyclic GMP levels and on the mRNA expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in...
... a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum ... Francis S H, Turko I V, Corbin J D. Cyclic nucleotide phosphodiesterases: relating structure and function. Prog Nucleic Acid ... penis erectile dysfunction icariin nitric oxide phosphodiesterase type 5 JIANG Zhaojian, male, born in 1968, Associate ... Effect of icariin on cyclic GMP levels and on the mRNA expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in ...https://link.springer.com/article/10.1007%2Fs11596-006-0421-y
JCI Insight - Blocking MHC class II on human endothelium mitigates acute rejection
Functional regulatory T cells produced by inhibiting cyclic nucleotide phosphodiesterase type 3 prevent allograft rejection. ... If development into CTL occurs within the graft, the question arises as to which types of graft cells stimulate this process. ... Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion. ... or type III (transmural arteritis) (44). The presence and degree of such vascular lesions is reported to correlate with the ...https://insight.jci.org/articles/view/85293
Sulindac sulfide selectively inhibits growth and induces apoptosis of human breast tumor cells by phosphodiesterase 5...
3′,5′-Cyclic nucleotide phosphodiesterase in tumor cells as potential target for tumor growth inhibition. Cancer Res 1993;53: ... Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med ... Cyclic nucleotide phosphodiesterases as targets for treatment of haematological malignancies. Biochem J 2006;393:21-41. ... Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev 1995;75:725-48. ...https://mct.aacrjournals.org/content/8/12/3331
Tehranolide inhibits cell proliferation via calmodulin inhibition, PDE, and PKA activation | SpringerLink
Cyclic nucleotide phosphodiesterases: relating structure and function. Prog Nucleic Acid Res Mol Biol. 2001;65:1-52.PubMed ... Marika S, Ve´ronique M, Sylvie B, Manuel R. Sildenafil and vardenafil, types 5 and 6 phosphodiesterase inhibitors, induce ... 3,5-cyclic-nucleotide PDE, 2-mM cyclic AMP, and 100 μM CaM in 0.5 ml of Tris buffer solution (40 mM Tris-chloride, 0.1 mM MnCl2 ... Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents. Ann Rev Pharmacol Toxicol. 1977;17: ...https://link.springer.com/article/10.1007/s13277-013-1031-5
Type 3 Cyclic Nucleotide Phosphodiesterases Medicine & Life Sciences Knockout Mice Medicine & Life Sciences ... XIA, W., Pessentheiner, A., Walenta, E., Rülicke, T., Schreiber, R., Hofer, D., Amor, M. & Bogner-Strauß, J. G., 7 Mar 2017, ( ... 7, p. 1948-1961 14 p.. Research output: Contribution to journal › Article › Research › peer-review ...https://graz.pure.elsevier.com/en/persons/melina-amor
Table of Contents - January 01, 2006, 393 (1) | Biochemical Journal
Cyclic nucleotide phosphodiesterases as targets for treatment of haematological malignancies Adam Lerner, Paul M. Epstein ... The shed ectodomain of type XIII collagen associates with the fibrillar fibronectin matrix and may interfere with its assembly ... Biochemical Journal Jan 01, 2006, 393 (1) 7-20; DOI: https://doi.org/10.1042/BJ20051578 ...http://www.biochemj.org/content/393/1
- Type 3 phosphodiesterase inhibitors may be protective against cerebrovascular events in patients with claudication. (ebi.ac.uk)
- Finally, S14 neuroprotective effects were reversed by blocking the cAMP signaling pathways that operate through cAMP-dependent protein kinase A. [Conclusions/Significance]: Our findings demonstrate that phosphodiesterase 7 inhibition can protect dopaminergic neurons against different insults, and they provide support for the therapeutic potential of phosphodiesterase 7 inhibitors in the treatment of neurodegenerative disorders, particularly Parkinson disease. (csic.es)
- 1. The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN - BD11, were characterized using calcium/calmodulin, IGF-1, isoenzyme-selective PDE inhibitors and RT - PCR. (strath.ac.uk)
- Our earliest understanding of phosphodiesterase (PDE) inhibitors began with a series of publications by Sutherland and Rall in the 1950s, describing the properties of cyclic adenosine monophosphate (cAMP). (beds.ac.uk)
- By the 1960s, the role of cyclic nucleotide second messengers, such as cAMP, in cell signaling and homeostasis was established, and regulation of this pathway by PDE inhibitors arose as a field of considerable interest. (beds.ac.uk)
- Background: Phosphodiesterase 4 (PDE4) inhibitors negatively modulate many inflammatory responses, and some of these pharmacological effects are mediated by inhibition of PDE4B in inflammatory cells. (thefreelibrary.com)
- sup] By increasing intracellular cAMP level, phosphodiesterase 4 (PDE4) inhibitors are being developed as anti-inflammatory agents for the treatment of chronic inflammatory disorders such as asthma, chronic obstructive pulmonary disease, and psoriasis. (thefreelibrary.com)
- Several different lines of evidence suggest that a COX-independent mechanism may be fully or partially responsible for the antineoplastic activities of NSAIDs and COX-2-selective inhibitors ( 7 - 12 ). (aacrjournals.org)
- Treatment opportunities involving phosphodiesterase inhibitors (PDEIs) and purinergic modulators may plausibly exist. (iacfsme.org)
- Even though cGMP binding to the catalytic site stimulates cyclic-nucleotide binding to the allosteric [ 5 ] sites, inhibitors do not elicit the same function. (ijddr.in)
- Currently there are three (Sildenafil, vardenafil and tadalafil) Phosphodiesterase type-5 inhibitors (PDE5-i) used in the treatment of male ED [ 6 ]. (ijddr.in)
- EHNA (erythro-9-(2-hydroxy-3-nonyl)adenine) is a potent adenosine deaminase inhibitor, which also acts as a phosphodiesterase inhibitor that selectively inhibits phosphodiesterase type 2 (PDE2). (wikipedia.org)
- Elevation of the second messenger cyclic adenosine monophosphate (cAMP) in macrophages suppresses several inflammatory responses, including inflammatory mediator production and receptor-mediated phagocytosis. (thefreelibrary.com)
- Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. (nih.gov)
- It is based on adenosine triphosphate (ATP) and its derivatives, ADP and adenosine as well as the purine nucleotide UTP. (iacfsme.org)
- There are two important secondary messengers that regulate many physiological processes i.e., 3′,5′-cyclic adenosine monophosphate (cAMP) and 3′,5′-cyclic guanosine monophosphate (cGMP). (ijddr.in)
- The cyclic nucleotide phosphodiesterases (PDE) comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. (ebi.ac.uk)
- Retinal 3',5'-cGMP phosphodiesterase is located in photoreceptor outer segments: it is light activated, playing a pivotal role in signal transduction. (ebi.ac.uk)
- Recently, EHNA was shown to block the activity of purified soluble cGMPstimulated phosphodiesterase (PDE2) from frog, human, and porcine heart with an apparent Ki value of approximately 1 microM and with negligible effects on Ca2+/calmodulin PDE (PDE1), cGMP-inhibited PDE (PDE3), and low Km cAMP-specific PDE (PDE4) (Méry, P.F., C. Pavoine, F. Pecker, and R. Fischmeister. (ubi.pt)
- Most of the effects of the signaling molecule nitric oxide (NO) are mediated by cGMP, which is synthesized by soluble guanylyl cyclase and degraded by phosphodiesterases. (rupress.org)
- Here we show that in platelets and aortic tissue, NO led to a biphasic response characterized by a tremendous increase in cGMP (up to 100-fold) in less than 30 s and a rapid decline, reflecting the tightly controlled balance of guanylyl cyclase and phosphodiesterase activities. (rupress.org)
- Furthermore, this increase in cGMP degradation is paralleled by the phosphorylation of phosphodiesterase type 5 at Ser-92. (rupress.org)
- Thus, our data suggest that NO-induced desensitization of the cGMP response is caused by the phosphorylation and subsequent activity increase of phosphodiesterase type 5. (rupress.org)
- Furthermore, the effects of ICA on the mRNA expression of specific cGMP-binding phosphodiesterase type V (PDE5) in rat penis were also observed. (springer.com)
- Effects OF Sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro. (springer.com)
- Soderling S H, Beavo J A. Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions. (springer.com)
- Expression of three isoforms of cGMP-biding cGMP-Specific phosphodiesterase (PDE5) in human penile cavernosum. (springer.com)
- Here, we show that sulindac sulfide (SS) induces apoptosis and inhibits the growth of human breast tumor cells with IC 50 values of 60 to 85 μmol/L. Within the same concentration range, SS inhibited cyclic GMP (cGMP) hydrolysis in tumor cell lysates but did not affect cyclic AMP hydrolysis. (aacrjournals.org)
- The effect of cGMP (cyclic GMP) dependent protein kinase 1-β (PKG1-β) and cGMP analogues on transcriptional activity and replication of human immunodeficiency virus type 1 (HIV-1) was investigated. (biomedcentral.com)
- According to their specificity toward hydrolysis of cyclic AMP (CAMP) or cyclic GMP (cGMP) can be grouped into 11 families [ 2 ]. (ijddr.in)
- 7. These findings, in a clonal insulin secreting cell line, are consistent with an important role for PDE3B in regulating the pool of cyclic AMP relevant to the modulation of glucose-induced insulin secretion. (strath.ac.uk)
- Type 1 diabetes (T1D) is caused by the immune system inappropriately attacking the cells in the pancreas that produce insulin, the hormone that controls blood sugar levels. (psychcentral.com)