Compounds which inhibit or antagonize the biosynthesis or actions of 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.
A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.
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, some members of this class have additional specificity for 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)
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.
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 and EC EC 3.1.4.-.
Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.
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.
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.
Compounds that specifically inhibit PHOSPHODIESTERASE 4.
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)
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, members of this class have additional specificity for CYCLIC GMP.
Compounds that specifically inhibit PHOSPHODIESTERASE 3.
A phosphodiesterase 4 inhibitor with antidepressant properties.
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.
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 KINASES
Compounds that specifically inhibit PHOSPHODIESTERASE 5.
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.
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.
Inhibitor of phosphodiesterases.
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.
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.
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.
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.
The rate dynamics in chemical or physical systems.
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)
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.
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.
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.
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.
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.
An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC
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)
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
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.
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.
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.
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
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.
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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
Specialized cells that detect and transduce light. They are classified into two types based on their light reception structure, the ciliary photoreceptors and the rhabdomeric photoreceptors with MICROVILLI. Ciliary photoreceptor cells use OPSINS that activate a PHOSPHODIESTERASE phosphodiesterase cascade. Rhabdomeric photoreceptor cells use opsins that activate a PHOSPHOLIPASE C cascade.
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.
Purine bases found in body tissues and fluids and in some plants.
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.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A heterotrimeric GTP-binding protein that mediates the light activation signal from photolyzed rhodopsin to cyclic GMP phosphodiesterase and is pivotal in the visual excitation process. Activation of rhodopsin on the outer membrane of rod and cone cells causes GTP to bind to transducin followed by dissociation of the alpha subunit-GTP complex from the beta/gamma subunits of transducin. The alpha subunit-GTP complex activates the cyclic GMP phosphodiesterase which catalyzes the hydrolysis of cyclic GMP to 5'-GMP. This leads to closure of the sodium and calcium channels and therefore hyperpolarization of the rod cells. EC 3.6.1.-.
Purines attached to a RIBOSE and a phosphate that can polymerize to form DNA and RNA.
Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.
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.
Nucleotides in which the base moiety is substituted with one or more sulfur atoms.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The process of cleaving a chemical compound by the addition of a molecule of water.
The portion of a retinal rod cell situated between the ROD INNER SEGMENT and the RETINAL PIGMENT EPITHELIUM. It contains a stack of photosensitive disk membranes laden with RHODOPSIN.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A phosphodiesterase that specifically cleaves the 3'-phosphate linkage of 2',3'-cyclic nucleotides. It is found at high level in the cytoplasm of cells that form the MYELIN SHEATH.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A cyclic nucleotide formed from CYTIDINE TRIPHOSPHATE by the action of cytidylate cyclase. It is a potential cyclic nucleotide intracellular mediator of signal transductions.
A group of enzymes within the class EC 3.6.1.- that catalyze the hydrolysis of diphosphate bonds, chiefly in nucleoside di- and triphosphates. They may liberate either a mono- or diphosphate. EC 3.6.1.-.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A drug combination that contains THEOPHYLLINE and ethylenediamine. It is more soluble in water than theophylline but has similar pharmacologic actions. It's most common use is in bronchial asthma, but it has been investigated for several other applications.
Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.
A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.
A subgroup of cyclic nucleotide-regulated ION CHANNELS of the superfamily of pore-loop cation channels that are opened by hyperpolarization rather than depolarization. The ion conducting pore passes SODIUM, CALCIUM, and POTASSIUM cations with a preference for potassium.
Photosensitive afferent neurons located in the peripheral retina, with their density increases radially away from the FOVEA CENTRALIS. Being much more sensitive to light than the RETINAL CONE CELLS, the rod cells are responsible for twilight vision (at scotopic intensities) as well as peripheral vision, but provide no color discrimination.
The sum of the weight of all the atoms in a molecule.
Established cell cultures that have the potential to propagate indefinitely.
A genus of protozoa, formerly also considered a fungus. Its natural habitat is decaying forest leaves, where it feeds on bacteria. D. discoideum is the best-known species and is widely used in biomedical research.
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.
Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.
Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.
A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.
The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
Elements of limited time intervals, contributing to particular results or situations.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A purine base and a fundamental unit of ADENINE NUCLEOTIDES.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
Pyrimidines with a RIBOSE and phosphate attached that can polymerize to form DNA and RNA.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A species of the family Ranidae (true frogs). The only anuran properly referred to by the common name "bullfrog", it is the largest native anuran in North America.
Cell surface proteins that bind cyclic AMP with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized cyclic AMP receptors are those of the slime mold Dictyostelium discoideum. The transcription regulator CYCLIC AMP RECEPTOR PROTEIN of prokaryotes is not included nor are the eukaryotic cytoplasmic cyclic AMP receptor proteins which are the regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASES.
The relationships of groups of organisms as reflected by their genetic makeup.
(11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
An ENTEROTOXIN from VIBRIO CHOLERAE. It consists of two major protomers, the heavy (H) or A subunit and the B protomer which consists of 5 light (L) or B subunits. The catalytic A subunit is proteolytically cleaved into fragments A1 and A2. The A1 fragment is a MONO(ADP-RIBOSE) TRANSFERASE. The B protomer binds cholera toxin to intestinal epithelial cells, and facilitates the uptake of the A1 fragment. The A1 catalyzed transfer of ADP-RIBOSE to the alpha subunits of heterotrimeric G PROTEINS activates the production of CYCLIC AMP. Increased levels of cyclic AMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells.
Proteins prepared by recombinant DNA technology.
Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Separation technique in which the stationary phase consists of ion exchange resins. The resins contain loosely held small ions that easily exchange places with other small ions of like charge present in solutions washed over the resins.
A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.
A diverse group of agents, with unique chemical structures and biochemical requirements, which generate NITRIC OXIDE. These compounds have been used in the treatment of cardiovascular diseases and the management of acute myocardial infarction, acute and chronic congestive heart failure, and surgical control of blood pressure. (Adv Pharmacol 1995;34:361-81)
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
A potent vasodilator agent that increases peripheral blood flow.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
Proteins which bind calmodulin. They are found in many tissues and have a variety of functions including F-actin cross-linking properties, inhibition of cyclic nucleotide phosphodiesterase and calcium and magnesium ATPases.
Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.
Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)
Proteins found in any species of bacterium.
That phase of a muscle twitch during which a muscle returns to a resting position.
A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-.
A phenothiazine with actions similar to CHLORPROMAZINE. It is used as an antipsychotic and an antiemetic.
A non-hydrolyzable analog of GTP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It binds tightly to G-protein in the presence of Mg2+. The nucleotide is a potent stimulator of ADENYLYL CYCLASES.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
A phosphodiesterase inhibitor which inhibits platelet aggregation. Formerly used as an antineoplastic.
A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
The functional hereditary units of BACTERIA.
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.
The state of the PENIS when the erectile tissue becomes filled or swollen (tumid) with BLOOD and causes the penis to become rigid and elevated. It is a complex process involving CENTRAL NERVOUS SYSTEM; PERIPHERAL NERVOUS SYSTEMS; HORMONES; SMOOTH MUSCLES; and vascular functions.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
Mercury-containing benzoic acid derivatives.
A component of PHOSPHATIDYLCHOLINES or LECITHINS, in which the two hydroxy groups of GLYCEROL are esterified with fatty acids. (From Stedman, 26th ed) It counteracts the effects of urea on enzymes and other macromolecules.
Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
Genotypic differences observed among individuals in a population.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
A positive inotropic cardiotonic (CARDIOTONIC AGENTS) with vasodilator properties, phosphodiesterase 3 inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell.
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.
A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
A type of ion exchange chromatography using diethylaminoethyl cellulose (DEAE-CELLULOSE) as a positively charged resin. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC
Transport proteins that carry specific substances in the blood or across cell membranes.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
Drugs used to cause dilation of the blood vessels.
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
A group of pyrido-indole compounds. Included are any points of fusion of pyridine with the five-membered ring of indole and any derivatives of these compounds. These are similar to CARBAZOLES which are benzo-indoles.
A potent phosphodiesterase inhibitor proposed as an antipsychotic agent.
Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.
The nonstriated involuntary muscle tissue of blood vessels.
The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra.
A METHYLXANTHINE derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production.
A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).
Phosphate esters of THYMIDINE in N-glycosidic linkage with ribose or deoxyribose, as occurs in nucleic acids. (From Dorland, 28th ed, p1154)
Drugs that selectively bind to and activate beta-adrenergic receptors.
A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).
The inability in the male to have a PENILE ERECTION due to psychological or organ dysfunction.
A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.
A transcriptional regulator in prokaryotes which, when activated by binding cyclic AMP, acts at several promoters. Cyclic AMP receptor protein was originally identified as a catabolite gene activator protein. It was subsequently shown to regulate several functions unrelated to catabolism, and to be both a negative and a positive regulator of transcription. Cell surface cyclic AMP receptors are not included (CYCLIC AMP RECEPTORS), nor are the eukaryotic cytoplasmic cyclic AMP receptor proteins, which are the regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASES.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.
Unstable isotopes of phosphorus that decay or disintegrate emitting radiation. P atoms with atomic weights 28-34 except 31 are radioactive phosphorus isotopes.
The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.
A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): ... Paraxanthine is a selective inhibitor of cGMP-preferring phosphodiesterase (PDE9) activity and is hypothesized to increase ... Paraxanthine is a competitive nonselective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits ... Paraxanthine is a phosphodiesterase type 9 (PDE9) inhibitor and it is sold as a research molecule for this same purpose. ...
Cyclic-nucleotide 3'-phosphodiesterase (CNPase). *List of human cell types derived from the germ layers ... 115 (2): 535-51. PMID 1425339.. *^ Yokoo H, Nobusawa S, Takebayashi H, Ikenaka K, Isoda K, Kamiya M, Sasaki A, Hirato J, ... doi:10.1016/S0002-9440(10)63730-3. PMC 1615653. PMID 15111318.. CS1 maint: multiple names: authors list (link) ... Oligodendrocytes do this by creating the myelin sheath.[1] A single oligodendrocyte can extend its processes to 50 axons,[2] ...
"Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic Nucleotide ... cyclic nucleotide phosphodiesterase (PDE2) on guinea pig left atria in eu- and hyperthyroidism" (PDF). Gen Physiol Biophys. 22 ... "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. Rev. 58 (3): 488-520. doi:10.1124/pr. ... "cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes". J. Clin. ...
Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule-associated protein and membrane anchor for tubulin". ... 3 (10): 1738-1739, 1742. doi:10.1128/mcb.3.10.1738. PMC 370035. PMID 6646120. Mill, F. D.; Naus, C. C.; Durand, M.; Bloom, F. E ... 3.0.CO;2-L. PMID 9722999. Oakley BR (December 2000). "An abundance of tubulins". Trends in Cell Biology. 10 (12): 537-42. doi: ... 105 (6 Pt 2): 3065-73. doi:10.1083/jcb.105.6.3065. PMC 2114727. PMID 3693406. Cowan NJ, Dobner PR, Fuchs EV, Cleveland DW ( ...
"Isozyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythro-9-(2-hydroxy-3-nonyl) adenine ... adenine inhibits cyclic GMP-stimulated phosphodiesterase in isolated cardiac myocytes". Molecular Pharmacology. 48 (1): 121-30 ... which also acts as a phosphodiesterase inhibitor that selectively inhibits phosphodiesterase type 2 (PDE2). "Sigma Aldrich". ... EHNA (erythro-9-(2-hydroxy-3-nonyl)adenine) is a potent adenosine deaminase inhibitor, ...
... cyclic nucleotide 3'-phosphodiesterase, and myelin proteins in rat forebrain subfractions during development". Neurochem. Res. ... 119 (3): 421-7. doi:10.1093/oxfordjournals.jbchem.a021258. PMID 8830034. Tsuda M, Egashira M, Niikawa N, et al. (2000). "Cancer ... 52 (3): 951-8. doi:10.1016/0006-291X(73)91029-2. PMID 4710574. Farrell DF, McKhann GM (1971). "Characterization of cerebroside ... 264 (2): 1252-9. PMID 2562955. Fleischer B, Zambrano F (1973). "Localization of cerebroside-sulfotransferase activity in the ...
Cyclic-nucleotide 3'-phosphodiesterase (CNPase) List of human cell types derived from the germ layers Carlson, Neil (2010). ... 115 (2): 535-51. PMID 1425339. Yokoo H, Nobusawa S, Takebayashi H, Ikenaka K, Isoda K, Kamiya M, Sasaki A, Hirato J, Nakazato Y ... 5 (3): 180-9. doi:10.1016/s1071-9091(98)80033-8. PMID 9777676. Káradóttir et al., 2007 Tkachev D, Mimmack ML, Ryan MM, et al. ( ... 3.0.CO;2-3. PMID 10679785. Pérez-Cerdá, Fernando; Sánchez-Gómez, María Victoria; Matute, Carlos (2015). "Pío del Río Hortega ...
Lefièvre L, de Lamirande E, Gagnon C (2003). "Presence of cyclic nucleotide phosphodiesterases PDE1A, existing as a stable ... cyclic nucleotide phosphodiesterase 1A is an enzyme that in humans is encoded by the PDE1A gene. GRCh38: Ensembl release 89: ... cyclic nucleotide phosphodiesterases". J Biol Chem. 271 (2): 796-806. doi:10.1074/jbc.271.2.796. PMID 8557689. Michibata H, ... "Entrez Gene: PDE1A phosphodiesterase 1A, calmodulin-dependent". Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and ...
2007). "Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes". J. Biol. Chem. 282 (45): 32749-57. doi:10.1074/ ... Rybalkin SD, Rybalkina I, Beavo JA, Bornfeldt KE (2002). "Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth ... cyclic nucleotide phosphodiesterase 1C is an enzyme that in humans is encoded by the PDE1C gene. GRCh38: Ensembl release 89: ... cyclic nucleotide phosphodiesterases". J Biol Chem. 271 (2): 796-806. doi:10.1074/jbc.271.2.796. PMID 8557689. "Entrez Gene: ...
Cyclic-nucleotide 3'-phosphodiesterase and multiple molecules of the Immune system. GRCh38: Ensembl release 89: ENSG00000197971 ... 47 (2): 614-6. doi:10.1111/j.1471-4159.1986.tb04544.x. PMID 2426402. Roth HJ, Kronquist K, Pretorius PJ, et al. (1986). " ... 3: 96-9. doi:10.4024/18SH03R.jbpc.03.03. This article incorporates text from the United States National Library of Medicine, ... The Golli mRNAs contain 3 exons unique to Golli-MBP, spliced in-frame to 1 or more MBP exons. They encode hybrid proteins that ...
Fell, David A. (1980). "Theoretical analyses of the functioning of the high- and low-Km cyclic nucleotide phosphodiesterases in ... and low-Km cyclic nucleotide phosphodiesterases on the regulation of adenosine 3',5'-cyclic monophosphate (cAMP) From the early ... cyclic monophosphate in animal cells". Journal of Theoretical Biology. 84 (2): 361-385. doi:10.1016/s0022-5193(80)80011-7. ISSN ... El-Yassin, D I; Fell, D A; Lloyd, B B; Fisher, R B (1979). "The breakdown of 2,3-bis(phospho)-D-glycerate by Fe(III)- ...
Cyclic-nucleotide 3'-phosphodiesterase, a myelin-associated enzyme that makes up 4% of total CNS myelin protein Chronic ... a proposed class of living organisms smaller than the accepted lower limit size for life 2',3'- ...
Cyclic-nucleotide 3'-phosphodiesterase. Moreover, oligodendrocytes also developed and migrated into fiber bundles in mice when ... 560 (1-3): 192-8. doi:10.1016/S0014-5793(04)00086-9. PMID 14988021. Tan, Y; Xie, Z; Ding, M; Wang, Z; Yu, Q; Meng, L; Zhu, H; ... 137 (2): 740-5. PMC 218351. PMID 370098. van der Heyden, MA; Defize, LH (2003-05-01). "Twenty one years of P19 cells: what an ... 3 (12): 2271-9. doi:10.1128/mcb.3.12.2271. PMC 370098. PMID 6656766. McBurney, MW; Reuhl, KR; Ally, AI; Nasipuri, S; Bell, JC; ...
... cyclic-nucleotide phosphodiesterase MeSH D08.811.277.352.640.160 - 2',3'-cyclic-nucleotide phosphodiesterases MeSH D08.811. ... cyclic nucleotide-regulated protein kinases MeSH D08.811.913.696.620.682.700.150.125 - cyclic amp-dependent protein kinases ... cyclic-GMP phosphodiesterase MeSH D08.811.277.352.640.150 - 3',5'- ... cyclic gmp-dependent protein kinases MeSH D08.811.913.696.620.682.700.150.575 - protamine kinase MeSH D08.811.913.696.620.682. ...
... cyclic-nucleotide phosphodiesterase EC now EC EC now EC EC now EC EC ... glucose-1-phospho-D-mannosylglycoprotein phosphodiesterase EC cyclic-guanylate-specific phosphodiesterase EC ... cyclic-GMP phosphodiesterase EC now with EC EC 2',3'-cyclic-nucleotide 3'-phosphodiesterase EC 3.1 ... cyclic-AMP phosphodiesterase EC N-acetylphosphatidylethanolamine-hydrolysing phospholipase D EC dGTPase EC ...
"Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase". The Journal ... "Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase". The Journal ... Zhang HT (2009). "Cyclic AMP-specific phosphodiesterase-4 as a target for the development of antidepressant drugs". Current ... Némoz G, Zhang R, Sette C, Conti M (Apr 1996). "Identification of cyclic AMP-phosphodiesterase variants from the PDE4D gene ...
"Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling". ... Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are ... "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 ...
... cyclic nucleotide phosphodiesterases". J. Biol. Chem. 271 (2): 796-806. doi:10.1074/jbc.271.2.796. PMID 8557689. Aizawa Y, ... 2001). "Human Ca2+/calmodulin-dependent phosphodiesterase PDE1A: novel splice variants, their specific expression, genomic ... 60 Suppl 3 (Suppl 3): iii18-24. doi:10.1136/ard.60.90003.iii18 (inactive 2021-01-14). PMC 1766679. PMID 11890646.CS1 maint: DOI ... 1517 (2): 278-87. doi:10.1016/s0167-4781(00)00293-1. PMID 11342109. Paulukat J, Bosmann M, Nold M, et al. (2001). "Expression ...
"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 ... Bender AT, Beavo JA (September 2006). "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. ... cyclic nucleotide phosphodiesterase (PDE2) on guinea pig left atria in eu- and hyperthyroidism" (PDF). Gen Physiol Biophys. 22 ...
cAMP's role in this process terminates upon hydrolysis to AMP by phosphodiesterase. Cyclic nucleotides are well-suited to act ... The two most well-studied cyclic nucleotides are cyclic AMP (cAMP) and cyclic GMP (cGMP), while cyclic CMP (cCMP) and cyclic ... A cyclic nucleotide (cNMP) is a single-phosphate nucleotide with a cyclic bond arrangement between the sugar and phosphate ... Finally, cyclic nucleotides can be distinguished from non-cyclic nucleotides because they are smaller and less polar. The ...
Numerous cyclic nucleotide phosphodiesterases (PDE) can degrade cGMP by hydrolyzing cGMP into 5'-GMP. PDE 5, -6 and -9 are cGMP ... Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second ... cyclic monophosphate (8-Br-cGMP) Francis SH, Corbin JD (August 1999). "Cyclic nucleotide-dependent protein kinases: ... R. Lane Brown; Timothy Strassmaier; James D. Brady; Jeffrey W. Karpen (2006). "The Pharmacology of Cyclic Nucleotide-Gated ...
... nucleotide phosphodiesterases". Biochemical Pharmacology. 21 (18): 2443-50. doi:10.1016/0006-2952(72)90414-5. PMID 4345859. ... a potent new inhibitor of cyclic 3',5'- ... and as a phosphodiesterase inhibitor selective for the PDE4 ... and characterization of human cAMP-specific phosphodiesterase (PDE4) subtypes A, B, C, and D". Biochemical and Biophysical ... ISBN 3-540-66127-1. Progress in Drug Research / Volume 31 (Progress in Drug Research). Boston: Birkhauser. 1987. p. 526. ISBN 3 ...
He is best known for his work with cyclic nucleotide phosphodiesterases. He was the first to propose, based on his experimental ... one on the potential therapeutic application of cyclic nucleotides: (Weiss, Benjamin, ed., Cyclic Nucleotides in Disease[1]), ... Cyclic Nucleotide Phosphodiesterases: Weiss and co-workers developed rapid phosphodiesterease assays [3, 4], separated ... Weiss, B. and Winchurch, R.A.: Analyses of cyclic nucleotide phosphodiesterases in lymphocytes from normal and aged leukemic ...
Johner A, Kunz S, Linder M, Shakur Y, Seebeck T (March 2006). "Cyclic nucleotide specific phosphodiesterases of Leishmania ... "Characterization of cyclic nucleotide phosphodiesterase isoforms associated to isolated cardiac nuclei". Biochimica et ... cyclic-AMP phosphodiesterase (EC, cAMP-specific phosphodiesterase, cAMP-specific PDE, PDE1, PDE2A, PDE2B, PDE4, PDE7, ... cyclic-AMP+phosphodiesterase at the US National Library of Medicine Medical Subject Headings (MeSH) Biology portal. ...
Nov 2003). "Structural evidence that brain cyclic nucleotide phosphodiesterase is a member of the 2H phosphodiesterase ... Helfman DM, Kuo JF (Jan 1982). "A homogeneous cyclic CMP phosphodiesterase hydrolyzes both pyrimidine and purine cyclic 2':3'- ... selectively activates the calcium-calmodulin sensitive isoform of cyclic nucleotide phosphodiesterase from human myometrium". ... "Purification to homogeneity and general properties of a novel phosphodiesterase hydrolyzing cyclic CMP and cyclic AMP". The ...
... cyclic nucleotide phosphodiesterase:3'-nucleotidase. This enzyme participates in purine metabolism and pyrimidine metabolism. ... ANRAKU Y (1964). "A NEW CYCLIC PHOSPHODIESTERASE HAVING A 3'-NUCLEOTIDASE ACTIVITY FROM ESCHERICHIA COLI B. I. PURIFICATION AND ... ANRAKU Y (1964). "A NEW CYCLIC PHOSPHODIESTERASE HAVING A 3'-NUCLEOTIDASE ACTIVITY FROM ESCHERICHIA COLI B. II. FURTHER STUDIES ... Center MS, Behal FJ (1968). "A cyclic phosphodiesterase with 3'-nucleotidase activity from Proteus mirabilis". J. Biol. Chem. ...
... cyclic nucleotide phosphodiesterase". Gene. 191 (1): 89-95. doi:10.1016/S0378-1119(97)00046-2. PMID 9210593. "Entrez Gene: ... Sadhu K, Hensley K, Florio VA, Wolda SL (1999). "Differential expression of the cyclic GMP-stimulated phosphodiesterase PDE2A ... cyclic phosphodiesterase is an enzyme that in humans is encoded by the PDE2A gene. GRCh38: Ensembl release 89: ENSG00000186642 ... PDE2A phosphodiesterase 2A, cGMP-stimulated". Witzenrath M, Gutbier B, Schmeck B, et al. (2005). "Phosphodiesterase 2 ...
September 2003). "Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system ... Lugnier C (March 2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific ... WO 03012030, Movsesian M, "Isoform-Selective Inhibitors and Activators of PDE3 Cyclic Nucleotide Phosphodiesterases", published ... Oocyte maturation inhibitor Bender AT, Beavo JA (September 2006). "Cyclic nucleotide phosphodiesterases: molecular regulation ...
... cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded by the PDE6B gene. PDE6 ... Journal of Cyclic Nucleotide Research. 2 (3): 139-48. PMID 6493. Keeler, CE (20 March 1928). "The Geotropic Reaction of Rodless ... Organization of the gene for the beta-subunit of human photoreceptor cyclic GMP phosphodiesterase]". Bioorganicheskaia Khimiia ... "In vivo differential prenylation of retinal cyclic GMP phosphodiesterase catalytic subunits". The Journal of Biological ...
Nov 2003). "Structural evidence that brain cyclic nucleotide phosphodiesterase is a member of the 2H phosphodiesterase ... Helfman DM, Kuo JF (Jan 1982). "A homogeneous cyclic CMP phosphodiesterase hydrolyzes both pyrimidine and purine cyclic 2:3- ... selectively activates the calcium-calmodulin sensitive isoform of cyclic nucleotide phosphodiesterase from human myometrium". ... "Purification to homogeneity and general properties of a novel phosphodiesterase hydrolyzing cyclic CMP and cyclic AMP". The ...
... cyclic nucleotide phosphodiesterase:3-nucleotidase. This enzyme participates in purine metabolism and pyrimidine metabolism. ... ANRAKU Y (1964). "A NEW CYCLIC PHOSPHODIESTERASE HAVING A 3-NUCLEOTIDASE ACTIVITY FROM ESCHERICHIA COLI B. I. PURIFICATION AND ... ANRAKU Y (1964). "A NEW CYCLIC PHOSPHODIESTERASE HAVING A 3-NUCLEOTIDASE ACTIVITY FROM ESCHERICHIA COLI B. II. FURTHER STUDIES ... Center MS, Behal FJ (1968). "A cyclic phosphodiesterase with 3-nucleotidase activity from Proteus mirabilis". J. Biol. Chem. ...
... cyclic nucleotide 3 phosphodiesterase ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations ... cyclic nucleotide 3 phosphodiesterase ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a well-established antibody ... Your search returned 34 2,3-cyclic nucleotide 3 phosphodiesterase ELISA ELISA Kit across 10 suppliers. ...
... cyclic nucleotide-3′-phosphodiesterase (CNPase) Original Russian Text © O.V. Krestinina, Yu.L. Baburina, I.V. Odinokova, T.S. ... Cyclic Nucleotide-3′-Phosphodiesterase in the Presence of Protoporphyrin IX in the Brain Mitochondria of Rats during the ... cyclic nucleotide-3′-phosphodiesterase (CNPase) increases. Here, we showed an increase in the degree of phosphorylation of ... 2.. Tan, D.-X., Manchester, L.C., Hardeland, R., Lopez-Burillo, S., Mayo, J.C., Sainz, R.M., and Reiter, R.J., J. Pineal Res., ...
Please allow 2-3 weeks for delivery. Upon receipt of an order each kit is assembled and tested to ensure that it meets ... Product Description: Immunotag™ Human CNP (2,3-cyclic-nucleotide 3-phosphodiesterase) ELISA ...
... cyclic-nucleotide phosphodiesterases in the dictionary. Meaning of 2,3-cyclic-nucleotide phosphodiesterases. ... cyclic-nucleotide phosphodiesterases mean? Information and translations of 2,3-cyclic-nucleotide phosphodiesterases in the ... cyclic-nucleotide phosphodiesterases inside other dictionary definitions.. Search inside. Are we missing a good definition for ... cyclic-nucleotide phosphodiesterases mean?. Definitions for 2,3-cyclic-nucleotide phosphodiesterases. Here are all the ...
... cyclic nucleotide-3′-phosphodiesterase trafficking. Authors: Zhang, B. Cao, Q.. Guo, A. Chu, H. Chan, Y.G.. Ling, E.A. Liang, F ... cyclic nucleotide-3′-phosphodiesterase trafficking. Proceedings of the National Academy of Sciences of the United States of ... Juxtanodin: An oligodendroglial protein that promotes cellular arborization and 2′,3′- ... An oligodendroglial protein that promotes cellular arborization and 2′,3′- ...
Cyclic nucleotide 3-phosphodiesterase (CNP), one of the promising candidate genes for schizophrenia, plays a key part in the ... Five CNP single nucleotide polymorphisms (SNPs) were investigated in a Chinese Han schizophrenia case-control sample set (n = ... Cyclic nucleotide 3-phosphodiesterase (CNP) is used as a marker protein of myelin-forming glial cells. In brain development, ... Cyclic nucleotide 3-phosphodiesterase (CNP), one of the promising candidate genes for schizophrenia, plays a key part in the ...
Cyclic-Nucleotide Phosphodiesterases. Myelin Proteins. Description. A phosphodiesterase that specifically cleaves the 3- ... cyclic nucleotides. It is found at high level in the cytoplasm of cells that form the MYELIN SHEATH.. Search for this term in ... Cyclic Nucleotide 3-Phosphodiesterase. Browse to parent terms:. 2,3- ...
... cyclic nucleotide 3-phosphodiesterase as a possible susceptibility gene for schizophrenia. Archives of general psychiatry 63 ( ... Cyclic nucleotide 3-phosphodiesterase is used as a marker of myelin-forming cells and is detectable in cells of ... cyclic nucleotide 3-phosphodiesterase (CNP) a candidate gene for schizophrenia. Reduced expression has been reported in the ... cyclic nucleotide 3-phosphodiesterase as a possible susceptibility gene for schizophrenia ...
Catalytic domain of mouse 2,3-cyclic nucleotide 3- phosphodiesterase, soaked with GTP ... cyclic nucleotide 3- phosphodiesterase, soaked with GTP. Coordinates. PDB Format Method. X-RAY DIFFRACTION 2.05 Å. Oligo State ... PHOSPHODIESTERASE: A. SMTL:PDB. SMTL Chain Id:. PDB Chain Id:. A. A ... 2xmi.1 , 2y1p.1 , 2y3x.1 , 2y3x.2 , 2y3x.3 , 2ydb.1 , 2ydd.1 , 2yoz.1 , 2yp0.1 , 5ae0.1 ...
... cyclic nucleotide phosphodiesterase. cGMP-specific phosphodiesterase PDE5A2. cGMP-specific phosphodiesterase type 5A. ... This gene encodes a cGMP-binding, cGMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family. ... PDEase_I; 35-cyclic nucleotide phosphodiesterase. * NM_033430.3 → NP_236914.2 cGMP-specific 3,5-cyclic phosphodiesterase ... PDEase_I; 35-cyclic nucleotide phosphodiesterase. * NM_033437.4 → NP_246273.2 cGMP-specific 3,5-cyclic phosphodiesterase ...
... at the cyaD1 locus that we predicted to encode a class III cytoplasmic phosphodiesterase. First, we have shown that spdA had a ... specific phosphodiesterase whose biological function remains elusive. Circumstantial evidence suggests that SpdA may contribute ... In contrast, 2′, 3′cAMP was unable to promote Clr specific-binding to DNA and activate smc02178 target gene expression ex ... 3′, 5′cAMP signaling in Sinorhizobium meliloti was recently shown to contribute to the autoregulation of legume infection. In ...
... cyclic phosphodiester to an RNA 2-phosphomonoester (PubMed:25239919). In vitro, can also ligate 5 and 3 half-tRNA molecules ... cyclic phosphate and 5-hydroxyl termini, respectively, to the product containing the 2-5 phosphodiester linkage. This ... cyclic-nucleotide 3-phosphodiesterase activity Source: EcoCyc ,p>Inferred from Direct Assay,/p> ,p>Used to indicate a direct ... cyclic phosphodiesteraseAdd BLAST. 175. Proteomic databases. PaxDb, a database of protein abundance averages across all three ...
... cyclic nucleotide 3′-phosphodiesterase modulates cell morphology. J. Neurosci. Res. 39, 386 - 397. *Wiley Online Library , ... phosphodiesterase isoform 2 and identification of specifically phosphorylated serine residues. J. Neurochem. 74, 540 - 546. * ... cyclic nucleotide 3′-phosphodiesterase (CNP), myelin/OL basic protein and the tight junction protein claudin-11 (formerly ... 3. M. Uruse, M. Yamamoto, M. Sugawa, K. Matsuura, Y. Sato, C. Seiwa, K. Watanabe, S. Aiso, H. Asou, Phase separation of myelin ...
... phosphodiesterase;. MBP,. myelin basic protein;. β-gal,. β-galactosidase. ... phosphodiesterase (CNPase; Sternberger Monoclonals) and myelin basic protein (MBP; gift of D. Colman, Mt. Sinai School of ... 5-bromo-4-chloro-3-indolyl β-d-galactoside;. KA,. kainic acid;. ICC,. immunocytochemistry;. LM,. light microscopic;. DIC,. ... 2 F-I). Donor-derived cells meeting these criteria stained positively with antibodies to NF, NSE, and NeuN (Fig. 4 E-I). ...
... phosphodiesterase (CNPase) is an enigmatic enzyme specifically expressed at high levels in the vertebrate myelin sheath, whose ... and a C-terminal phosphodiesterase domain. In order to be able to fully characterize CNPase structurally and functionally, we ... Structural evidence that brain cyclic nucleotide phosphodiesterase is a member of the 2H phosphodiesterase superfamily. J Biol ... Sakamoto Y, Tanaka N, Ichimiya T, Kurihara T, Nakamura KT: Three-dimensional structure of a cyclic-nucleotide phosphodiesterase ...
Cyclic-Nucleotide Phosphodiesterases / Phosphotyrosine / Hippocampus Language: English Journal: Experimental & Molecular ... Cyclic-Nucleotide Phosphodiesterases / Phosphotyrosine / Hippocampus Language: English Journal: Experimental & Molecular ... Cyclic-Nucleotide Phosphodiesterases/metabolism , Aging/physiology , Animals , Cells, Cultured , Hippocampus/cytology , ... cyclic nucleotide 3-phosphodiesterase with the rat foreb Nonspecific association of 2,3-cyclic nucleotide 3- ...
... phosphodiesterase and is involved in regulation and control of mitochondrial Ca2+. *A Galvita. 1. , ... cyclic nucleotide 3-phosphodiesterase and is involved in regulation and control of mitochondrial Ca2+. Cell Commun Signal 7, ... cyclic nucleotide 3-phosphodiesterase (CNP) has been shown to be associated with mitochondria, but the exact role of CNP in ... The neuron-specific protein, p42IP4 (Centaurin-α1) is localized in mitochondria, interacts with 2,3-cyclic nucleotide 3- ...
... cyclic nucleotide 3 phosphodiesterase; MHC, myosin heavy chain. Adapted from ref 19: Glorioso C, Sibille E. Between destiny ... Figure 2.. Age-dependent biological changes in neurons and glia. Known age-related cellular phenotypes are highlighted for ... Figure 3.. Dendritic inhibition, a biological module at the intersection of age and psychiatric disorders. A) Excitatory ... CRF, Corticotropin-releasing hormone; CALB-1, calbindin 1; SOD2, superoxide dismutase 2; BCL-2, B-cell CLL/lymphoma 2; DRD1, ...
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators ... calmodulin-dependent cyclic-nucleotide phosphodiesterase activity Source: MGIInferred from sequence orthologyi*7568196 ... Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators ... Belongs to the cyclic nucleotide phosphodiesterase family. PDE1 subfamily.Curated. Phylogenomic databases. evolutionary ...
Cyclic Nucleotide 3Phosphodiesterase (CNPase). The second or the third sets of slides of the first series from 3 and 4 mm ... phosphodiesterase immunocytochemistry showed an evident reduction in astrogliosis and enhanced survival of oligodendrocytes. ... 3. (a) Lack of significant effect of minocycline (total dose of 495 mg/kg per rat over 5 days) on lesion volume at the injury ... 3 c and d ), where neural cell apoptosis was found to be active during similar post-SCI time courses (35, 36). More importantly ...
... cyclic nucleotide phosphodiesterase activity.. J. Biol. Chem. 283 30942-9 2008. Matange N, Podobnik M, Visweswariah SS. ... 5-cyclic adenosine monophosphate phosphodiesterase CpdA (IPR026575). *Vacuolar protein sorting-associated protein 29 (IPR028661 ... Metallophosphatases (MPPs), also known as metallophosphoesterases, phosphodiesterases (PDEs), binuclear metallophosphoesterases ... 2,3-cyclic-nucleotide 2-phosphodiesterase/3-nucleotidase (IPR006294). *NAD pyrophosphatase/5-nucleotidase NadN (IPR006420) ...
"Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic Nucleotide ... cyclic nucleotide phosphodiesterase (PDE2) on guinea pig left atria in eu- and hyperthyroidism" (PDF). Gen Physiol Biophys. 22 ... "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. Rev. 58 (3): 488-520. doi:10.1124/pr. ... "cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes". J. Clin. ...
Cyclic-Nucleotide Phosphodiesterases / metabolism * Animals * Bisbenzimidazole / metabolism * Blotting, Western / methods * ...
Cyclic nucleotide 3′-phosphodiesterase Rn.31762 3163 373 8.5 Cdh2 Cadherin 2, type 1, N-cadherin (neuronal) Rn.17239 2342 289 ... 2, A to D). Cells also migrated in the general direction of beads soaked in GDNF (Fig. 2E). This is consistent with reports ... Table 2. Comparison of the expression of selected genes in E14.5 gut NCSCs and whole fetuses by microarray analysis, qRT-PCR, ... 2. GDNF signaling promotes gut NCSC migration and is required for the migration of NCSCs intothe intestines. [(A) to(E)] In ...
... cyclic nucleotide 3′-phosphodiesterase (CNPase), found in differentiated oligodendrocytes; and β-III tubulin, expressed in ... phosphodiesterase (CNPase), and β-III tubulin; other functionally related markers may additionally and/or alternatively be ... Example 2. Establishment of in Vivo Glioma Model and NSC Inoculation. Six to eight week old C57B1/6 mice (obtained from Charles ... 3. The isolated stem cell of claim 2, wherein said isolated stem cell exhibits an A2B5 astrocytic precursor marker. 4. The ...
Cyclic-nucleotide 3-phosphodiesterase (CNPase). *List of human cell types derived from the germ layers ... 115 (2): 535-51. PMID 1425339.. *^ Yokoo H, Nobusawa S, Takebayashi H, Ikenaka K, Isoda K, Kamiya M, Sasaki A, Hirato J, ... doi:10.1016/S0002-9440(10)63730-3. PMC 1615653. PMID 15111318.. CS1 maint: multiple names: authors list (link) ... Oligodendrocytes do this by creating the myelin sheath.[1] A single oligodendrocyte can extend its processes to 50 axons,[2] ...
... cyclic-nucleotide 3′-phosphodiesterase (CNP; catalog #836401, BioLegend; RRID: AB_510037), 1:1000 MBP (catalog #808402, ... 3D,E), there was no difference in the number of ATF4+/Sox10+ cells in MCH versus control brains (Fig. 3F,G). We also saw no ... 3C), and no evidence of increased CHOP+/Sox10+ cells in MCH brains (Fig. 3H,I). Our results suggest that while increased ... 3D,E). Interestingly, the hypoxia-induced increase of p-eIF2α (Fig. 3A,B) was not accompanied by an increase in protein levels ...
... cyclic nucleotide phosphodiesterase (CNPase) (1:800; Covance), myelin basic protein (MBP) (1:50; Millipore Bioscience Research ... Data in B, D and H represent the mean ± SD (n = 3 in B and D and 6 in H). *p , 0.05. Scale bars: A, C, 50 μm; E, 500 μm; F, G, ... 2A,D). After differentiation with CNTF (Fig. 2B), IGF1 (Fig. 2C), NT3, NRG, or GDNF, the percentages of O1+ OLs were 41, 40, 18 ... 3D,E). The total number of OLs in the cultures with CNTF, NT3, IGF1, NRG, or GDNF was 4.6, 2, 2.8, 2.9, or 1.9 times greater ...
  • Sequence alignment of SpdA with cyclic adenosine monophosphate phosphodiesterases from Escherichia coli (CpdA), Mycobacterium tuberculosis (Rv0805) and Haemophilus influenzae (Icc) and S. meliloti . (
  • Rodent studies have consistently shown upregulation of the 3, 5-cyclic adenosine monophosphate (cAMP) system induced by different types of chronic but not acute antidepressant treatment including serotonin and norepinephrine uptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, lithium and electroconvulsions. (
  • cAMP is synthesized from adenosine 5-triphosphate (ATP) by adenylyl cyclase and metabolized by cyclic nucleotide phosphodiesterases (PDEs). (
  • Phosphodiesterase 4 (PDE4) inhibition restores the suppressive effects of 3′,5′-cyclic adenosine monophosphate in lymphocytes. (
  • The second messenger 3′,5′-cyclic adenosine monophosphate (cyclic-AMP) uses effector proteins to influence cell function and fate. (
  • CNPase catalyzes the following reaction: nucleoside 2',3'-cyclic phosphate + H2O ⇌ {\displaystyle \rightleftharpoons } nucleoside 2'-phosphate Thus, the two substrates of this enzyme are nucleoside 2',3'-cyclic phosphate and H2O, whereas its product is nucleoside 2'-phosphate. (
  • In enzymology, a 2',3'-cyclic-nucleotide 2'-phosphodiesterase (EC is an enzyme that catalyzes the chemical reaction nucleoside 2',3'-cyclic phosphate + H2O ⇌ {\displaystyle \rightleftharpoons } nucleoside 3'-phosphate Thus, the two substrates of this enzyme are nucleoside 2',3'-cyclic phosphate and H2O, whereas its product is nucleoside 3'-phosphate. (
  • The systematic name of this enzyme class is nucleoside-2',3'-cyclic-phosphate 3'-nucleotidohydrolase. (
  • A phosphodiesterase that specifically cleaves the 3'-phosphate linkage of 2',3'-cyclic nucleotides. (
  • 25239919 ). In vitro, can also ligate 5' and 3' half-tRNA molecules with 2',3'-cyclic phosphate and 5'-hydroxyl termini, respectively, to the product containing the 2'-5' phosphodiester linkage. (
  • Two different types of low-density detergent-insoluble glycosphingolipid-enriched membrane domain (DIG) fractions were isolated from myelin by extraction with Triton X-100 (TX-100) in 50 mM sodium phosphate buffer at room temperature (20°C) (procedure 1), in contrast to a single low-density fraction obtained by extraction with TX-100 in Tris buffer containing 150 mM NaCl and 5 mM EDTA at 4°C (procedure 2). (
  • This protein specifically recognizes two second messengers, the membrane lipid PtdIns (3,4,5)P3 and the soluble inositol phosphate Ins(1,3,4,5)P4. (
  • Nucleoside 3',5'-cyclic phosphate + H 2 O = nucleoside 5'-phosphate. (
  • A phosphate-binding histidine of binuclear metallophosphodiesterase enzymes is a determinant of 2',3'-cyclic nucleotide phosphodiesterase activity. (
  • this pathway results in production of a mature tRNA in which the phosphodiester bond linking the 5′‐ and 3′‐half molecules is derived from the 2′-3′ cyclic phosphate generated by the splicing endonuclease. (
  • The phosphate moiety linking the 5′‐ and 3′‐half molecules in this pathway is derived from the γ‐phosphate of guanosine triphosphate GTP used to activate the 5′‐half molecule, and the 2′‐phosphate must be removed by the action of the 2′‐phosphotransferase . (
  • 1993) An NAD derivative produced during transfer RNA splicing: ADP‐ribose 1″‐2″ cyclic phosphate. (
  • 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. (
  • These are purine nucleotides in which the oxygen atoms linked to the C3 and C5 carbon atoms of the ribose moiety are both bonded the same phosphorus atom of the phosphate group. (
  • Inorganic phosphate (P i ), or orthophosphate (PO 4 3− ), can serve as a direct source of P for essentially all physiological groups of microorganisms in both natural environments and laboratory media. (
  • Among components of the cAMP pathway, PDE4 appears to be critical for antidepressant effects because an inhibitor of PDE4, 4-[3-(cyclopenotoxyl)-4-methoxyphenyl]-2-pyrrolidone (rolipram), showed antidepressant effects both in animals and humans, and various forms of antidepressant treatment induced increase in PDE4 in rodents. (
  • The COX-2 inhibitor parecoxib is neuroprotective but not antiepileptogenic in the pilocarpine model of temporal lobe epilepsy. (
  • : another tyrosine kinase inhibitor (TKI) drug with 2 symmetrical N atoms. (
  • Here, we review a decade-long exploration of the contribution of cyclic-AMP and PDE4 to the pathogenesis of B-cell lymphoma, 5 ⇓ ⇓ ⇓ - 9 culminating with the first-in-cancer clinical trial of a PDE4 inhibitor in advanced B-cell malignancies. (
  • Furthermore, the effects of cAMP itself and two derivatives on both processes were converted from weak to strong by addition of a phosphodiesterase inhibitor. (
  • A similar preincubation in ATP or in 8-bromoadenosine 3':5'-cyclic monophosphoric acid plus the phosphodiesterase inhibitor methyl isobutyl xanthine led to a partial loss of EA rosetting of cells on plain fibrin and to a partial reversal of the effects of 2dG seen with cells on complexes. (
  • In addition, induction of PAI was enhanced by isobutyl-methylxanthine, a phosphodiesterase inhibitor, but not, however, by other phosphodiesterase inhibitors, or by forskolin or N(G)-nitro-L-arginine, suggesting an effect of isobutyl-methylxanthine other than through cyclic nucleotides. (
  • Bucladesine is a cyclic nucleotide derivative which mimics the action of endogenous cAMP and is a phosphodiesterase inhibitor. (
  • The two histidine and two aspartic acid residues, which bind zinc are conserved among all studied PDEs (See review article [3] ). (
  • In PDEs that are selective for either cAMP or cGMP, this glutamine is constrained by neighboring residues to a position favoring selectivity for either cyclic nucleotide . (
  • cGMP-driven activation of protein kinases, ion channels, or phosphodiesterases (PDEs) causes a broad variety of physiological responses whereas dysregulation can result in severe pathologies. (
  • 1 The synthesis and degradation of cyclic-AMP are tightly controlled by 2 classes of enzymes, adenylyl cyclases and phosphodiesterases (PDEs), respectively. (
  • The proposed mechanism of CNPases phosphodiesterase catalytic activity is similar to the second step of the reaction mechanism for RNase A. CNPase is expressed exclusively by oligodendrocytes in the CNS, and the appearance of CNPase seems to be one of the earliest events of oligodendrocyte differentiation. (
  • For human immunodeficiency virus type 1 (HIV-1), in vitro experiments have shown that its tropism may be narrow and limited to humans and chimpanzees because its replication in other non-human primate species is hindered by factors such as TRIM5α (tripartite motif 5 alpha), APOBEC3G (apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3), and tetherin. (
  • 2015. Determinants of ligand binding and catalytic activity in the myelin enzyme 2′,3′-cyclic nucleotide 3′-phosphodiesterase. (
  • 2] The catalytic version of the reaction was developed by Nikolay Zinin in the late 1830s,[3][4] and the reaction mechanism for this organic reaction was proposed in 1903 by A. J. Lapworth. (
  • 2',3'-Cyclic-nucleotide 3'-phosphodiesterase also known as CNPase is an enzyme that in humans is encoded by the CNP gene. (
  • The cGMP-Degrading Enzyme Phosphodiesterase-5 (PDE5) in Cerebral Small Arteries of Older People. (
  • 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) is an enigmatic enzyme specifically expressed at high levels in the vertebrate myelin sheath, whose function and physiological substrates are unknown. (
  • 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) is an enzyme expressed abundantly in myelin. (
  • The enzymatic activity of CNPase, the hydrolysis of 2',3'-cyclic nucleotides to 2'-nucleotides, was the basis of the discovery of the enzyme from brain tissue in the 1960s [ 12 ]. (
  • The PDE2 (phosphodiesterase 2) enzyme is one of 21 different phosphodiesterases (PDE) found in mammals . (
  • Shp2, an Src-homology 2 domain (SH2)-containing tyrosine phosphatase, is a widely expressed intracellular enzyme that regulates signaling events downstream of several growth factor/cytokine receptors in various cell types ( 8 , 18 ). (
  • Myllykoski M, Itoh K, Kangas SM, Heape AM, Kang S-U, Lubec G, Kursula I, Kursula P. The N-terminal domain of the myelin enzyme 2´,3´-cyclic nucleotide 3´-phosphodiesterase: Direct molecular interaction with the calcium sensor calmodulin. (
  • One of the cyclic nucleotide derivatives tested, 8-parachlorophenylthio cAMP, exhibited dramatically higher potency (ED 50 for kinase activation and enzyme induction ≅ 2-3 µM) than N 6 ,O 2 '-dibutyryl cAMP (ED 50 ≅ 100 µM). (
  • Inhibition of PDE5A1 guanosine cyclic monophosphate (cGMP) hydrolysing activity by sildenafil analogues that inhibit cellular cGMP efflux. (
  • Cyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. (
  • 2 , 3 The therapeutic utility of controlling the intracellular levels of cyclic-AMP, and of cyclic guanosine monophosphate (cyclic-GMP), with PDE inhibitors is well established. (
  • 2',3'-Cyclic nucleotide 3'-phosphodiesterase ( CNP ) is used as a marker protein of myelin-forming glial cells. (
  • The protein consists of two domains: an uncharacterized N-terminal domain with little homology to other proteins, and a C-terminal phosphodiesterase domain. (
  • The 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), a protein of unknown function in vivo, is abundantly expressed in myelinating glia in two isoforms , CNP1 and CNP2. (
  • Furthermore, glial fibrillary acidic protein and 2′,3′ cyclic nucleotide 3′ phosphodiesterase immunocytochemistry showed an evident reduction in astrogliosis and enhanced survival of oligodendrocytes. (
  • 4. The isolated stem cell of claim 2, wherein said isolated stem cell exhibits a glial fibrillary acidic protein (GFAP) astrocytic precursor marker. (
  • MECP2 (methyl-CpG binding protein 2) is in many mammals an important regulator of neuronal function and development. (
  • Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. (
  • The activator protein (AP)-2α transcription factor plays a crucial role in the progression of several human tumors, including malignant melanoma, prostate, and breast cancer. (
  • The transcription factor activator protein (AP)-2α has been shown to regulate many of the genes that are involved in normal cellular hemostasis. (
  • AP-2α is a 52-kDa protein mapped to the short arm of chromosome 6 near the HLA locus (1) , a common molecular abnormality found in human astrocytomas. (
  • The AP-2α protein binds to a consensus palindromic core recognition element via a DNA-binding domain located within the COOH-terminal half of the protein (2) . (
  • Reduced levels of the myelin protein 2′-3′-cyclic nucleotide 3′-phosphodiesterase (CNP) are associated with the schizophrenic symptom catatonia in both humans and mouse models. (
  • Isoflurane reduces pain and inhibits apoptosis of myocardial cells through the phosphoinositide 3-kinase/protein kinase B signaling pathway in mice during cardiac surgery. (
  • Myelin basic protein has been shown to interact in vivo with Proteolipid protein 1, and in vitro with Calmodulin, Actin, Tropomyosin, Tubulin, Clathrin, 2',3'-Cyclic-nucleotide 3'-phosphodiesterase and multiple molecules of the Immune system. (
  • Precursor tRNA transcripts (top) contain 5′‐leader and 3′‐trailer sequences (dark blue) that must be removed before function in protein synthesis, and some tRNA species also contain introns (red) that must be removed by splicing. (
  • Glial cell types were identified by morphology and immunoreactivity (IR) with antibodies directed against glial fibrillary acidic protein (GFAP), cyclic nucleotide phosphodiesterase (CNP), or myelin basic protein (MBP). (
  • Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), vimentin and 2 ′ , 3 ′ -cyclic nucleotide 3 ′ -phosphodiesterase (CNPase) were analysed through Western blotting of hydrocephalic CSF samples (n = 17) and compared with data from CSF of normal infants without neurological deficits (n = 8). (
  • A variety of cyclic nucleotide derivatives were tested for their ability to activate cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC ) and to induce tyrosine aminotransferase (L-tyrosine: 2-oxoglutarate aminotransferase, EC ) in intact Reuber H35 rat hepatoma cells. (
  • The ratio of protein kinase activity toward a mixed histone preparation ± cAMP in 10,000 x g supernatant fractions of H35 cells incubated with or without a number of different cyclic nucleotide derivatives was used as an index of the degree of protein kinase activation in the intact cells. (
  • The increase in the protein kinase activity ratio generated by each cyclic nucleotide derivative preceded that in aminotransferase activity, a pattern to be expected if a cause-effect relationship exists. (
  • The lesions consisted of ovoid to elongated cells that were positive for Vimentin, S100-protein (Figure 3 ) and myelin basic protein (MBP) (Figure 4 ) but did not react for 2',3'-Cyclic-Nucleotide 3'-Phosphodiesterase (CNP). (
  • Nevertheless, intracerebral schwannoma displayed a similar storiform growth pattern, cytological appearance and abundant presence of reticulin fibers (compare Figure 7 with Figure 2 ) and it was also positive for S100-protein (compare Figure 8 with Figure 3 ). (
  • Context Convergent data make 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) a candidate gene for schizophrenia. (
  • This gene encodes a cGMP-binding, cGMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family. (
  • Gene expression profiles have been described for uncultured hematopoietic stem cells and cultured central nervous system neurospheres ( 2 - 8 ), but not for prospectively identified, uncultured neural stem cells. (
  • Open in a separate window Figure 3 Gene expression of nuclear thyroid hormone receptors, TR and TR, and plasma membrane integrin v3 in PBMC from healthy donors and from both hyperthyroid and euthyroid GD patients. (
  • Table 3 Correlation between gene expression of the receptors for VIP and for thyroid hormone in PBMC. (
  • AP-2α, which is regulated by cyclic AMP and retinoic acid (3) , mediates programmed gene expression during both embryonic morphogenesis and adult cell differentiation (4) . (
  • Therefore, loss of AP-2α expression may contribute to functional changes of several gene products that in normal cells are involved in cellular proliferation and differentiation. (
  • These mRNAs arise from the long MBP gene (otherwise called "Golli-MBP") that contains 3 additional exons located upstream of the classic MBP exons. (
  • Alternative splicing from the Golli and the MBP transcription start sites gives rise to 2 sets of MBP-related transcripts and gene products. (
  • Polymorphisms in the interleukin 3 gene show strong association with susceptibility to Graves' disease in Chinese population. (
  • Using a transgenic mouse, we show that NG2 proteoglycan-positive progenitor cells that express the 2',3'-cyclic nucleotide 3'-phosphodiesterase gene display a multipotent phenotype in vitro and generate electrically excitable neurons, as well as astrocytes and oligodendrocytes. (
  • in the presence of PPIX, the phosphorylation of 2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNPase) increases. (
  • The physiological substrate for the enzymatic reaction of CNPase has been a mystery, because 2',3'-cyclic nucleotides have not been discovered in vivo . (
  • The 20-residue extension in the N-terminus of CNPase 2 functions as a mitochondrial targeting signal that is controlled by phosphorylation [ 16 ]. (
  • CNPase (2', 3'-cyclic nucleotide 3'-phosphodiesterase [or -phosphohydrolase], EC is present in very high levels in brain and peripheral nerve. (
  • This phosphodiesterase specifically hydrolyzes cGMP to 5'-GMP. (
  • Distinct phosphodiesterase 5A-containing compartments allow selective regulation of cGMP-dependent signalling in human arterial smooth muscle cells. (
  • Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. (
  • Some are cAMP ( figure 1 ) selective hydrolases (PDE 4, -7 and -8), others are cGMP ( figure 1 ) selective hydrolases (PDE 5, -6 and -9) and the rest can hydrolyse both cAMP and cGMP (PDE1, -2, -3, -10 and -11). (
  • As mentioned above, PDE2 is able to hydrolyze both cAMP and cGMP ( figure 1 ), whereas some other members of the PDE family are selective for either of the two cyclic nucleotides. (
  • Increased hydrolysis of cAMP due to binding of cGMP to the GAF-B domain is well documented, however there are no known examples for the reverse (See review article [3] ). (
  • It has been shown that PDE2 lowers cAMP through increased cGMP caused by atrial natriuretic peptide (ANP) resulting in decreased aldosterone secretion (See review article [3] ). (
  • This compound belongs to the class of organic compounds known as 3',5'-cyclic purine nucleotides. (
  • 2',3'-Cyclic nucleotide 3'-phosphodiesterase ( CNP ), one of the promising candidate genes for schizophrenia, plays a key part in the oligodendrocyte function and in myelination. (
  • Recientes caracterizaciones en los cambios en la expresión génica dependiente de la edad han mostrado que el envejecimiento del cerebro humano requiere de un conjunto específico de vías biológicas en un continuo a través del curso de toda la vida, y que los mismos genes que están asociados con el envejecimiento normal se implican frecuentemente y de igual forma en la depresión como en otros trastornos cerebrates. (
  • Loss of AP-2α results in deregulation of several genes with AP-2α binding motifs such as E-cadherin , p21 WAF1 , MMP-2 , MCAM/MUC18 , VEGF , and c-KIT . (
  • AP-2α expression correlates inversely with glioma grade, suggesting a direct role in glioma tumorigenicity, possibly through subsequent deregulation of target genes. (
  • AP-2α plays a pivotal role in regulating the expression of several genes, the products of which are involved in tumor growth and metastasis. (
  • It is involved in the regulation of intracellular concentrations of cyclic nucleotides and is important for smooth muscle relaxation in the cardiovascular system. (
  • 6 Mechanistically, PDE4 inhibition resulted in elevation of intracellular cyclic-AMP levels and suppression of PI3K and AKT activity. (
  • Mass spectrometry analysis of the extracellular proteome of MR-1 identified one putative endonuclease (SO1844), a predicted UshA (bifunctional UDP-sugar hydrolase/5′ nucleotidase), a predicted PhoX (calcium-activated alkaline phosphatase), and a predicted CpdB (bifunctional 2′,3′ cyclic nucleotide 2′ phosphodiesterase/3′ nucleotidase), all of which could play important roles in the extracellular degradation of DNA under phosphorus-limiting conditions. (
  • Recent evidence indicates that iron metabolism and iron-dependent tumor growth are promising targets for cancer treatment as tumor cells have an increased demand for iron to support ribonucleotide reductase activity and mitochondrial function ( 3 ). (
  • 4) Neutral membrane sphingomyelin phosphodiesterases, and 5) Glycerophosphodiester phosphodiesterases. (
  • Preferentially binds to alpha-2,3-linked sialic acid. (
  • Venkatesan R, Sah-Teli SK, Awoniyi LO, Jiang G, Prus P, Kastaniotis AJ, Hiltunen JK, Wierenga RK, Chen Z. Insights into mitochondrial fatty acid synthesis from the structure of heterotetrameric 3-ketoacyl-ACP reductase/3R-hydroxyacyl-CoA dehydrogenase. (
  • NB: [ 'Tyrosine is not an alcohol but a phenol, since its hydroxyl group is bonded directly to an aromatic ring, giving it different acid/base and oxidative properties). (
  • The microarray included normal brain tissue, and AP-2α expression was determined by immunohistochemistry. (
  • Myllykoski M, Raasakka A, Han H, Kursula P. Myelin 2´,3´-cyclic nucleotide 3´-phosphodiesterase: Active-site ligand binding and molecular conformation. (
  • 42 , 43 Cyclic-AMP (cAMP) downmodulates this positive signaling wave by suppressing SYK and PI3Kδ activity. (
  • Type 5 phosphodiesterase regulates glioblastoma multiforme aggressiveness and clinical outcome. (
  • 2 The most aggressive glioma is glioblastoma (GBM). (
  • 2 Gliomas, cancers arising from the most abundant glial cells, account for more than 14,000 of these cases. (
  • as well as two glial tumor cell lines were screened for the expression of glucocorticoid receptors using a mouse monoclonal antibody directed against rat liver GR (BuGR‐2). (
  • It is named for its ability to catalyze the phosphodiester hydrolysis of 2',3'-cyclic nucleotides to 2'-nucleotides, though a cohesive understanding of its specific physiologic functions are still ambiguous. (
  • The common variant in MTNR1B confers the risk of Type 2 diabetes and modulates FPG in both the Han Chinese and European populations. (
  • Chi FT, Jensen JK, Kozlova N, Samoylenko A, Kietzmann T. PAI-1 modulates cell migration in a LRP1-dependent manner via β-catenin and ERK1/2. (
  • Nitric oxide and cyclic nucleotide signal transduction modulates synaptic vesicle turnover in human model neurons. (
  • Belongs to the cyclic nucleotide phosphodiesterase family. (
  • The 2'-5' RNA ligase of Escherichia coli. (
  • In this concise review, we detail how PDE4 inhibition downmodulates the B-cell receptor (BCR)-related kinases spleen tyrosine kinase and phosphatidylinositol 3-kinase and inhibits vascular endothelial growth factor A secretion by tumor cells, inducing cancer cell apoptosis and blocking angiogenesis in the microenvironment. (
  • Binds 2 divalent metal cations per subunit. (
  • The assay identified novel promoters of OL differentiation which we attribute to (1) the incorporation of an OL toxicity pre-screen to allow lowering the concentrations of toxic compounds and (2) the utilization of freshly purified, non-passaged OPCs. (
  • It is noteworthy that the assay that we employed differs in some details from those reported by others including (1) an OL toxicity prescreen which enabled lowering the concentrations of toxic compounds and (2) the utilization of freshly purified, non-passaged OPCs. (
  • We have shown previously that down-regulation of AP-2α results in altered c-KIT and MCAM/MUC18 expression, both of which contribute to the increased metastatic potential of human malignant melanoma cells in vitro and in vivo (5) . (
  • De novo expression of transfected sirtuin 3 enhances susceptibility of human MCF-7 breast cancer cells to hyperoxia treatment. (
  • Indeed, stem cells seem to give the best chance for human tissue engineering, and particularly, mesenchymal stem cells (MSCs) represent a great tool in regenerative medicine because of their ability to differentiate into a variety of specialized cells in addition to their immuno-privileged characteristics [ 1 , 2 ]. (
  • We aimed to study the mRNA expression of interleukin (IL)-2, IL-4 and IL-5, the composition of the tumour infiltrating lymphocytes (TIL), and the expression of bcl-2 in 14 benign and malignant human parotid tumours. (
  • Recent discoveries that extend the potential use of ES cells include the isolation of ES cells from embryonic human tissue ( 2 ) and transplantation in sheep and mice of nuclei from mature tissues into enucleated oocytes, permitting the generation of ES cells from the same individual ( 3 ). (
  • Previous results suggest that signals involved in directed migration, differentiation, and integration normally seen during fetal corticogenesis can be re-expressed in postdevelopmental mouse neocortex if highly selective and noninflammatory apoptotic neuronal death is induced synchronously by targeted photolytic degeneration ( 3 , 4 ). (
  • One is a planar ring structure of the inhibitors, which align in the active site of the enzymes and the other is a conserved glutamine residue (the "glutamine switch" mentioned below), which is essential for nucleotide recognition and selectivity. (
  • 2 Department of Neurology, University of Göttingen , Robert-Koch-Strasse. (
  • The feasibility of using multipotent neural precursors to replace diseased neurons was tested in adult mouse neocortex with experimentally induced neurodegeneration using the approach of targeted photolytic neuronal degeneration ( 2 - 6 ). (
  • Targeted pyramidal neurons undergo apoptotic degeneration that is slowly progressive and noninflammatory, reaching a peak 8-10 days following induction of cell death, and continuing over 3-4 weeks ( 3 - 5 ). (
  • Immunocytochemistry revealed that CNP is detected, in a weak but punctate pattern, in dissociated rat hippocampal neurons of 3 days to 2 weeks in vitro . (
  • 2. Assuncao M, Santos-Marques MJ, de Freitas V, Carvalho F, Andrade JP, Lukoyanov NV, and Paula-Barbosa MM. Red wine antioxidants protect hippocampal neurons against ethanol-induced damage: a biochemical, morphological and behavioral study. (
  • A Matthews coefficient V M of 2.6 Å 3 Da -1 suggests that there are two molecules and 52.5% solvent content in the asymmetric unit. (
  • Five CNP single nucleotide polymorphisms (SNPs) were investigated in a Chinese Han schizophrenia case-control sample set (n = 180) using direct sequencing. (
  • Marked MMP-2 transcriptional up-regulation in mononuclear leukocytes invading the subarachnoidal space in aseptic suppurative Steroid-Responsive Meningitis Arteritis in dogs. (
  • Certain cytokines are involved in the generation of natural killer (NK) cells and participate in the regulation of the proto-oncogene bcl-2. (
  • M. Harris and Z. Fabry, "Initiation and Regulation of CNS Autoimmunity: Balancing Immune Surveillance and Inflammation in the CNS," Neuroscience and Medicine , Vol. 3 No. 3, 2012, pp. 203-224. (
  • few patients survive beyond 2 years from diagnosis ( 1 ). (
  • MOG-IgG serostatus was longitudinally assessed in seropositive patients with available serum samples and at least 2 years follow-up. (
  • Patients with MOG-IgG had neuromyelitis optica spectrum disorder (NMOSD, n=10), idiopathic AQP4-IgG-negative myelitis (n=4), idiopathic AQP4-IgG-negative optic neuritis (n=4), other demyelinating syndromes (n=3) and multiple sclerosis (n=1). (
  • Multiple sclerosis (MS) is a devastating neurological disease, affecting over 2 million patients worldwide, caused by autoimmune-mediated destruction of the myelin sheaths that insulate and protect axons in the central nervous system. (
  • High-dose simvastatin (Zocor) significantly reduced brain atrophy and slowed advancement of disability for 2 years in patients with secondary progressive multiple sclerosis, researchers said here. (
  • That prompted the current trial, in which patients with established secondary progressive MS were randomized to high-dose simvastatin or placebo for 2 years. (
  • Some 14% had experienced a relapse within the past year and 18% had had one within the previous 2 years, with a higher rate of such relapses in patients randomized to placebo. (
  • 2. Activation. (
  • In contrast, activation of the Jak/Stat pathway promotes gliogenesis with concomitant suppression of neurogenesis ( 2 , 15 ). (
  • The 3‐CCA end is added following 3′ end processing in organisms in which the CCA sequence is not genomically encoded. (
  • Multiple base and sugar nucleotide modifications (indicated by stars in the mature tRNA molecule) are added in a tRNA sequence and/or species specific manner. (
  • 0.001) of glioblastomas and anaplastic astrocytomas, respectively, compared with grade 2 astrocytomas and normal brain, all of which (100%) maintained expression of AP-2α. (
  • Fetal-onset ventriculomegally (enlarged ventricles without raised pressure) is thought to result in more severe brain damage [ 3 , 4 ] but recent studies challenge this notion [ 9 ] even though ventricular expansion, and consequential compression and stretching of the brain must have a damaging effect in severe cases. (
  • B. T. Hawkins and T. P. Davis, "The Blood-Brain Bar-rier/Neurovascular Unit in Health and Disease," Pharmacological Reviews, Vol. 57, No. 2, 2005, pp. 173-185. (
  • Brain MRI scans were performed 2 weeks before starting treatment, after 1 year, and after 2 years, with the final scan taken 30 days after the last drug dose. (
  • Chernyakov I, Whipple JM, Kotelawala L, Grayhack EJ and Phizicky EM (2008) Degradation of several hypomodified mature tRNA species in Saccharomyces cerevisiae is mediated by Met22 and the 5′‐3′ exonucleases Rat1 and Xrn1. (