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)Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Research Support as Topic: Financial support of research activities.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Cyclic GMP-Dependent Protein Kinase Type I: A cyclic GMP-dependent protein kinase subtype that is expressed in SMOOTH MUSCLE tissues and plays a role in regulation of smooth muscle contraction. Two isoforms, PKGIalpha and PKGIbeta, of the type I protein kinase exist due to alternative splicing of its mRNA.Cyclic GMP-Dependent Protein Kinase Type II: A cyclic GMP-dependent protein kinase subtype that is expressed predominantly in INTESTINES, BRAIN, and KIDNEY. The protein is myristoylated on its N-terminus which may play a role its membrane localization.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Cell Dedifferentiation: A reverse developmental process in which terminally differentiated cells with specialized functions revert back to a less differentiated stage within their own CELL LINEAGE.Aorta: The main trunk of the systemic arteries.Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Microfilament Proteins: Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.PhosphoproteinsCell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.Fendiline: Coronary vasodilator; inhibits calcium function in muscle cells in excitation-contraction coupling; proposed as antiarrhythmic and antianginal agents.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Nitric Oxide Synthase Type III: A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in ENDOTHELIAL CELLS.Nitric Oxide: 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.Genes, ras: Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.AMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.Nitric Oxide Synthase Type II: A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.Tyrosine 3-Monooxygenase: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Privacy: The state of being free from intrusion or disturbance in one's private life or affairs. (Random House Unabridged Dictionary, 2d ed, 1993)Confidentiality: The privacy of information and its protection against unauthorized disclosure.Computer Security: Protective measures against unauthorized access to or interference with computer operating systems, telecommunications, or data structures, especially the modification, deletion, destruction, or release of data in computers. It includes methods of forestalling interference by computer viruses or so-called computer hackers aiming to compromise stored data.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Journal Impact Factor: A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.Informed Consent: Voluntary authorization, by a patient or research subject, with full comprehension of the risks involved, for diagnostic or investigative procedures, and for medical and surgical treatment.Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.Hypertension: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.Bibliometrics: The use of statistical methods in the analysis of a body of literature to reveal the historical development of subject fields and patterns of authorship, publication, and use. Formerly called statistical bibliography. (from The ALA Glossary of Library and Information Science, 1983)Journalism, Medical: The collection, writing, and editing of current interest material on topics related to biomedicine for presentation through the mass media, including newspapers, magazines, radio, or television, usually for a public audience such as health care consumers.Gasotransmitters: Endogenously produced lipid-soluble gaseous molecules which function as neurotransmitters and signal mediators targeting ION CHANNELS and transporters.Hydrogen Cyanide: Hydrogen cyanide (HCN); A toxic liquid or colorless gas. It is found in the smoke of various tobacco products and released by combustion of nitrogen-containing organic materials.Hydrogen Sulfide: A flammable, poisonous gas with a characteristic odor of rotten eggs. It is used in the manufacture of chemicals, in metallurgy, and as an analytical reagent. (From Merck Index, 11th ed)Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Carbon Monoxide: Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed)Sulfur Dioxide: A highly toxic, colorless, nonflammable gas. It is used as a pharmaceutical aid and antioxidant. It is also an environmental air pollutant.Oxidoreductases Acting on CH-NH2 Group Donors: Enzymes catalyzing the dehydrogenation of or oxidation of compounds containing primary amines.Nitrous Oxide: Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream.Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals.Methane: The simplest saturated hydrocarbon. It is a colorless, flammable gas, slightly soluble in water. It is one of the chief constituents of natural gas and is formed in the decomposition of organic matter. (Grant & Hackh's Chemical Dictionary, 5th ed)rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Angiotensin II: An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.Angiotensin II Type 1 Receptor Blockers: Agents that antagonize ANGIOTENSIN II TYPE 1 RECEPTOR. Included are ANGIOTENSIN II analogs such as SARALASIN and biphenylimidazoles such as LOSARTAN. Some are used as ANTIHYPERTENSIVE AGENTS.Receptor, Angiotensin, Type 1: An angiotensin receptor subtype that is expressed at high levels in a variety of adult tissues including the CARDIOVASCULAR SYSTEM, the KIDNEY, the ENDOCRINE SYSTEM and the NERVOUS SYSTEM. Activation of the type 1 angiotensin receptor causes VASOCONSTRICTION and sodium retention.Receptor, Angiotensin, Type 2: An angiotensin receptor subtype that is expressed at high levels in fetal tissues. Many effects of the angiotensin type 2 receptor such as VASODILATION and sodium loss are the opposite of that of the ANGIOTENSIN TYPE 1 RECEPTOR.Receptors, Angiotensin: Cell surface proteins that bind ANGIOTENSINS and trigger intracellular changes influencing the behavior of cells.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Allosteric Site: A site on an enzyme which upon binding of a modulator, causes the enzyme to undergo a conformational change that may alter its catalytic or binding properties.Cyclic Nucleotide Phosphodiesterases, Type 5: A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in vascular tissue and plays an important role in regulating VASCULAR SMOOTH MUSCLE contraction.Atrial Natriuretic Factor: 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.Receptors, Atrial Natriuretic Factor: Cell surface proteins that bind ATRIAL NATRIURETIC FACTOR with high affinity and trigger intracellular changes influencing the behavior of cells. They contain intrinsic guanylyl cyclase activity.Endothelial Cells: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.Cells, Cultured: 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.Nitroprusside: 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.OxadiazolesPulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs.Superoxides: Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.Hydroxyeicosatetraenoic Acids: Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes.Constriction: The act of constricting.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1.NADPH Oxidase: A flavoprotein enzyme that catalyzes the univalent reduction of OXYGEN using NADPH as an electron donor to create SUPEROXIDE ANION. The enzyme is dependent on a variety of CYTOCHROMES. Defects in the production of superoxide ions by enzymes such as NADPH oxidase result in GRANULOMATOUS DISEASE, CHRONIC.Hypertension, Pulmonary: Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.12-Hydroxy-5,8,10,14-eicosatetraenoic Acid: A lipoxygenase metabolite of ARACHIDONIC ACID. It is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumor cell metastatic potential through activation of protein kinase C. (J Pharmacol Exp Ther 1995; 274(3):1545-51; J Natl Cancer Inst 1994; 86(15):1145-51)Calcium Channels, L-Type: Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.Guinea Pigs: 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.Calcium Channel Agonists: Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Adenosine Triphosphate: 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.Heart Ventricles: The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.Ion Channels: 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.Estrogens: Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.Receptors, Estrogen: Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.Estrogen Receptor alpha: One of the ESTROGEN RECEPTORS that has marked affinity for ESTRADIOL. Its expression and function differs from, and in some ways opposes, ESTROGEN RECEPTOR BETA.Estradiol: The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.Estrogen Receptor beta: One of the ESTROGEN RECEPTORS that has greater affinity for ISOFLAVONES than ESTROGEN RECEPTOR ALPHA does. There is great sequence homology with ER alpha in the DNA-binding domain but not in the ligand binding and hinge domains.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Nitric Oxide Synthase Type I: A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in NERVE TISSUE.Thioredoxins: Hydrogen-donating proteins that participates in a variety of biochemical reactions including ribonucleotide reduction and reduction of PEROXIREDOXINS. Thioredoxin is oxidized from a dithiol to a disulfide when acting as a reducing cofactor. The disulfide form is then reduced by NADPH in a reaction catalyzed by THIOREDOXIN REDUCTASE.Estrogens, Conjugated (USP): A pharmaceutical preparation containing a mixture of water-soluble, conjugated estrogens derived wholly or in part from URINE of pregnant mares or synthetically from ESTRONE and EQUILIN. It contains a sodium-salt mixture of estrone sulfate (52-62%) and equilin sulfate (22-30%) with a total of the two between 80-88%. Other concomitant conjugates include 17-alpha-dihydroequilin, 17-alpha-estradiol, and 17-beta-dihydroequilin. The potency of the preparation is expressed in terms of an equivalent quantity of sodium estrone sulfate.Pericytes: Unique slender cells with multiple processes extending along the capillary vessel axis and encircling the vascular wall, also called mural cells. Pericytes are imbedded in the BASEMENT MEMBRANE shared with the ENDOTHELIAL CELLS of the vessel. Pericytes are important in maintaining vessel integrity, angiogenesis, and vascular remodeling.Capillaries: The minute vessels that connect the arterioles and venules.Retinal Vessels: The blood vessels which supply and drain the RETINA.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.Fibroblast Growth Factor 2: A single-chain polypeptide growth factor that plays a significant role in the process of WOUND HEALING and is a potent inducer of PHYSIOLOGIC ANGIOGENESIS. Several different forms of the human protein exist ranging from 18-24 kDa in size due to the use of alternative start sites within the fgf-2 gene. It has a 55 percent amino acid residue identity to FIBROBLAST GROWTH FACTOR 1 and has potent heparin-binding activity. The growth factor is an extremely potent inducer of DNA synthesis in a variety of cell types from mesoderm and neuroectoderm lineages. It was originally named basic fibroblast growth factor based upon its chemical properties and to distinguish it from acidic fibroblast growth factor (FIBROBLAST GROWTH FACTOR 1).Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Angiogenesis Inhibitors: Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.Fraser Syndrome: Rare autosomal recessive congenital malformation syndrome characterized by cryptophthalmos, SYNDACTYLY and UROGENITAL ABNORMALITIES. Other anomalies of bone, ear, lung, and nose are common. Mutations on FRAS1 and FREM2 are associated with the syndrome.Quackery: The fraudulent misrepresentation of the diagnosis and treatment of disease.Allergy and Immunology: A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder.Hospices: Facilities or services which are especially devoted to providing palliative and supportive care to the patient with a terminal illness and to the patient's family.Medical Missions, Official: Travel by a group of physicians for the purpose of making a special study or undertaking a special project of short-term duration.Natural History: A former branch of knowledge embracing the study, description, and classification of natural objects (as animals, plants, and minerals) and thus including the modern sciences of zoology, botany, and mineralogy insofar as they existed at that time. In the 17th, 18th, and 19th centuries it was much used for the generalized pursuit of certain areas of science. (Webster, 3d ed; from Dr. James H. Cassedy, NLM History of Medicine Division)HistoryNaval Medicine: The practice of medicine concerned with conditions affecting the health of individuals associated with the marine environment.Syndactyly: A congenital anomaly of the hand or foot, marked by the webbing between adjacent fingers or toes. Syndactylies are classified as complete or incomplete by the degree of joining. Syndactylies can also be simple or complex. Simple syndactyly indicates joining of only skin or soft tissue; complex syndactyly marks joining of bony elements.Natriuretic Peptide, C-Type: A PEPTIDE of 22 amino acids, derived mainly from cells of VASCULAR ENDOTHELIUM. It is also found in the BRAIN, major endocrine glands, and other tissues. It shares structural homology with ATRIAL NATRIURETIC FACTOR. It has vasorelaxant activity thus is important in the regulation of vascular tone and blood flow. Several high molecular weight forms containing the 22 amino acids have been identified.Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.Chromaffin Cells: Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia (PARAGANGLIA, CHROMAFFIN) of the sympathetic nervous system.Adrenal Medulla: The inner portion of the adrenal gland. Derived from ECTODERM, adrenal medulla consists mainly of CHROMAFFIN CELLS that produces and stores a number of NEUROTRANSMITTERS, mainly adrenaline (EPINEPHRINE) and NOREPINEPHRINE. The activity of the adrenal medulla is regulated by the SYMPATHETIC NERVOUS SYSTEM.Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs.Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.Connectin: A giant elastic protein of molecular mass ranging from 2,993 kDa (cardiac), 3,300 kDa (psoas), to 3,700 kDa (soleus) having a kinase domain. The amino- terminal is involved in a Z line binding, and the carboxy-terminal region is bound to the myosin filament with an overlap between the counter-connectin filaments at the M line.Complement C6: A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.Protein Conformation: 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).Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Complement Factor I: A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.ColoradoFellowships and Scholarships: Stipends or grants-in-aid granted by foundations or institutions to individuals for study.Peritoneovenous Shunt: An operation for the continuous emptying of ascitic fluid into the venous system. Fluid removal is based on intraperitoneal and intrathoracic superior vena cava pressure differentials and is performed via a pressure-sensitive one-way valve connected to a tube traversing the subcutaneous tissue of the chest wall to the neck where it enters the internal jugular vein and terminates in the superior vena cava. It is used in the treatment of intractable ascites.Emergency Service, Hospital: Hospital department responsible for the administration and provision of immediate medical or surgical care to the emergency patient.Nephrons: The functional units of the kidney, consisting of the glomerulus and the attached tubule.Colorado tick fever virus: A species of COLTIVIRUS transmitted by the tick DERMACENTOR andersonii and causing fever, chills, aching head and limbs, and often vomiting. It occurs in the northwestern United States, except the Pacific Coast.History of MedicineColorado Tick Fever: A febrile illness characterized by chills, aches, vomiting, leukopenia, and sometimes encephalitis. It is caused by the COLORADO TICK FEVER VIRUS, a reovirus transmitted by the tick Dermacentor andersoni.Schools, Medical: Educational institutions for individuals specializing in the field of medicine.Fund Raising: Usually organized community efforts to raise money to promote financial programs of institutions. The funds may include individual gifts.Search Engine: Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.Asia: The largest of the continents. It was known to the Romans more specifically as what we know today as Asia Minor. The name comes from at least two possible sources: from the Assyrian asu (to rise) or from the Sanskrit usa (dawn), both with reference to its being the land of the rising sun, i.e., eastern as opposed to Europe, to the west. (From Webster's New Geographical Dictionary, 1988, p82 & Room, Brewer's Dictionary of Names, 1992, p34)Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.Information Storage and Retrieval: Organized activities related to the storage, location, search, and retrieval of information.User-Computer Interface: The portion of an interactive computer program that issues messages to and receives commands from a user.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Pseudoephedrine: A phenethylamine that is an isomer of EPHEDRINE which has less central nervous system effects and usage is mainly for respiratory tract decongestion.Ivermectin: A mixture of mostly avermectin H2B1a (RN 71827-03-7) with some avermectin H2B1b (RN 70209-81-3), which are macrolides from STREPTOMYCES avermitilis. It binds glutamate-gated chloride channel to cause increased permeability and hyperpolarization of nerve and muscle cells. It also interacts with other CHLORIDE CHANNELS. It is a broad spectrum antiparasitic that is active against microfilariae of ONCHOCERCA VOLVULUS but not the adult form.Filaricides: Pharmacological agents destructive to nematodes in the superfamily Filarioidea.Cyclic Nucleotide-Gated Cation Channels: A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.Caenorhabditis elegans: A species of nematode that is widely used in biological, biochemical, and genetic studies.Oxygen: An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.Caenorhabditis elegans Proteins: Proteins from the nematode species CAENORHABDITIS ELEGANS. The proteins from this species are the subject of scientific interest in the area of multicellular organism MORPHOGENESIS.Nucleotides, CyclicNeurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Oxygen Inhalation Therapy: Inhalation of oxygen aimed at restoring toward normal any pathophysiologic alterations of gas exchange in the cardiopulmonary system, as by the use of a respirator, nasal catheter, tent, chamber, or mask. (From Dorland, 27th ed & Stedman, 25th ed)Retinal Rod Photoreceptor Cells: 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.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Reagent Kits, Diagnostic: Commercially prepared reagent sets, with accessory devices, containing all of the major components and literature necessary to perform one or more designated diagnostic tests or procedures. They may be for laboratory or personal use.Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.Authorship: The profession of writing. Also the identity of the writer as the creator of a literary production.Knowledge Bases: Collections of facts, assumptions, beliefs, and heuristics that are used in combination with databases to achieve desired results, such as a diagnosis, an interpretation, or a solution to a problem (From McGraw Hill Dictionary of Scientific and Technical Terms, 6th ed).GuanineGranulocyte-Macrophage Progenitor Cells: The parent cells that give rise to both cells of the GRANULOCYTE lineage and cells of the monocyte/macrophage lineage.Editorial Policies: The guidelines and policy statements set forth by the editor(s) or editorial board of a publication.Scientific Misconduct: Intentional falsification of scientific data by presentation of fraudulent or incomplete or uncorroborated findings as scientific fact.Game Theory: Theoretical construct used in applied mathematics to analyze certain situations in which there is an interplay between parties that may have similar, opposed, or mixed interests. In a typical game, decision-making "players," who each have their own goals, try to gain advantage over the other parties by anticipating each other's decisions; the game is finally resolved as a consequence of the players' decisions.Dominica: An island republic of the West Indies. Its capital is Roseau. It was discovered in 1493 by Columbus and held at different times by the French and the British in the 18th century. A member of the West Indies Federation, it achieved internal self-government in 1967 but became independent in 1978. It was named by Columbus who discovered it on Sunday, Domingo in Spanish, from the Latin Dominica dies, the Lord's Day. (From Webster's New Geographical Dictionary, 1988, p338 & Room, Brewer's Dictionary of Names, 1992, p151)Cooperative Behavior: The interaction of two or more persons or organizations directed toward a common goal which is mutually beneficial. An act or instance of working or acting together for a common purpose or benefit, i.e., joint action. (From Random House Dictionary Unabridged, 2d ed)Platelet Aggregation: The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Thrombin: An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.Platelet Activation: A series of progressive, overlapping events, triggered by exposure of the PLATELETS to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.Receptor, Insulin: A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.Platelet Adhesiveness: The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces.Platelet Count: The number of PLATELETS per unit volume in a sample of venous BLOOD.Platelet Aggregation Inhibitors: Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.ExhibitionsExhibits as Topic: Discussions, descriptions or catalogs of public displays or items representative of a given subject.MuseumsHistory, 20th Century: Time period from 1901 through 2000 of the common era.History, 19th Century: Time period from 1801 through 1900 of the common era.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.DNA: 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).Publications: Copies of a work or document distributed to the public by sale, rental, lease, or lending. (From ALA Glossary of Library and Information Science, 1983, p181)Science: The study of natural phenomena by observation, measurement, and experimentation.National Institutes of Health (U.S.): An operating division of the US Department of Health and Human Services. It is concerned with the overall planning, promoting, and administering of programs pertaining to health and medical research. Until 1995, it was an agency of the United States PUBLIC HEALTH SERVICE.Biomedical Research: Research that involves the application of the natural sciences, especially biology and physiology, to medicine.Family Practice: A medical specialty concerned with the provision of continuing, comprehensive primary health care for the entire family.Research: Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)Academies and Institutes: Organizations representing specialized fields which are accepted as authoritative; may be non-governmental, university or an independent research organization, e.g., National Academy of Sciences, Brookings Institution, etc.Psychosomatic Medicine: A system of medicine which aims at discovering the exact nature of the relationship between the emotions and bodily function, affirming the principle that the mind and body are one.Saint Vincent and the Grenadines: A self-governing state of the Windward Islands in the West Indies, comprising Saint Vincent and the northern islets of the Grenadines. Its capital is Kingstown. It is one of the original homes of the Carib Indians supposed to have been sighted by Columbus in 1498. It was in English hands from 1627 till held by the French 1779-83. Saint Vincent subsequently became a British possession and, with other nearby British territories, was administered by the Governor of the Windward Islands till 1959. It attained a measure of independence in 1969 but achieved full independence as Saint Vincent and the Grenadines in 1979. Saint Vincent was the 4th century Spanish martyr on whose feast day Columbus discovered the island. Grenadines is derived from the Spanish kingdom of Granada. (From Webster's New Geographical Dictionary, 1988, p1054 & The Europa World Year Book 1993, p2441)Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Therapeutics: Procedures concerned with the remedial treatment or prevention of diseases.Myocardial Contraction: Contractile activity of the MYOCARDIUM.Shock, Septic: Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status.Caveolae: Endocytic/exocytic CELL MEMBRANE STRUCTURES rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in ENDOCYTOSIS (potocytosis), transcytosis, and SIGNAL TRANSDUCTION. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of CAVEOLINS.Caveolin 1: A tyrosine phosphoprotein that plays an essential role in CAVEOLAE formation. It binds CHOLESTEROL and is involved in LIPIDS transport, membrane traffic, and SIGNAL TRANSDUCTION.Caveolins: The main structural proteins of CAVEOLAE. Several distinct genes for caveolins have been identified.Cardiovascular Diseases: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Receptors, Scavenger: A large group of structurally diverse cell surface receptors that mediate endocytic uptake of modified LIPOPROTEINS. Scavenger receptors are expressed by MYELOID CELLS and some ENDOTHELIAL CELLS, and were originally characterized based on their ability to bind acetylated LOW-DENSITY LIPOPROTEINS. They can also bind a variety of other polyanionic ligand. Certain scavenger receptors can internalize micro-organisms as well as apoptotic cells.Scavenger Receptors, Class B: A family of scavenger receptors that are predominately localized to CAVEOLAE of the PLASMA MEMBRANE and bind HIGH DENSITY LIPOPROTEINS.Lipoproteins, HDL: A class of lipoproteins of small size (4-13 nm) and dense (greater than 1.063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is APOLIPOPROTEIN A-I. HDL also shuttle APOLIPOPROTEINS C and APOLIPOPROTEINS E to and from triglyceride-rich lipoproteins during their catabolism. HDL plasma level has been inversely correlated with the risk of cardiovascular diseases.

Nitric oxide modulates endothelin 1-induced Ca2+ mobilization and cytoskeletal F-actin filaments in human cerebromicrovascular endothelial cells. (1/1035)

A functional interrelation between nitric oxide (NO), the endothelial-derived vasodilating factor, and endothelin 1 (ET-1), the potent vasoconstrictive peptide, was investigated in microvascular endothelium of human brain. Nor-1 dose-dependently decreased the ET-1-stimulated mobilization of Ca2+. This response was mimicked with cGMP and abrogated by inhibitors of guanylyl cyclase or cGMP-dependent protein kinase G. These findings indicate that NO and ET-1 interactions involved in modulation of intracellular Ca2+ are mediated by cGMP/protein kinase G. In addition, Nor-1-mediated effects were associated with rearrangements of cytoskeleton F-actin filaments. The results suggest mechanisms by which NO-ET-1 interactions may contribute to regulation of microvascular function.  (+info)

Molecular identification of human G-substrate, a possible downstream component of the cGMP-dependent protein kinase cascade in cerebellar Purkinje cells. (2/1035)

G-substrate, an endogenous substrate for cGMP-dependent protein kinase, exists almost exclusively in cerebellar Purkinje cells, where it is possibly involved in the induction of long-term depression. A G-substrate cDNA was identified by screening expressed sequence tag databases from a human brain library. The deduced amino acid sequence of human G-substrate contained two putative phosphorylation sites (Thr-68 and Thr-119) with amino acid sequences [KPRRKDT(p)PALH] that were identical to those reported for rabbit G-substrate. G-substrate mRNA was expressed almost exclusively in the cerebellum as a single transcript. The human G-substrate gene was mapped to human chromosome 7p15 by radiation hybrid panel analysis. In vitro translation products of the cDNA showed an apparent molecular mass of 24 kDa on SDS/PAGE which was close to that of purified rabbit G-substrate (23 kDa). Bacterially expressed human G-substrate is a heat-stable and acid-soluble protein that cross-reacts with antibodies raised against rabbit G-substrate. Recombinant human G-substrate was phosphorylated efficiently by cGMP-dependent protein kinase exclusively at Thr residues, and it was recognized by antibodies specific for rabbit phospho-G-substrate. The amino acid sequences surrounding the sites of phosphorylation in G-substrate are related to those around Thr-34 and Thr-35 of the dopamine- and cAMP-regulated phosphoprotein DARPP-32 and inhibitor-1, respectively, two potent inhibitors of protein phosphatase 1. However, purified G-substrate phosphorylated by cGMP-dependent protein kinase inhibited protein phosphatase 2A more effectively than protein phosphatase 1, suggesting a distinct role as a protein phosphatase inhibitor.  (+info)

Phosphorylation of the inositol 1,4,5-trisphosphate receptor by cyclic nucleotide-dependent kinases in vitro and in rat cerebellar slices in situ. (3/1035)

We have examined cyclic nucleotide-regulated phosphorylation of the neuronal type I inositol 1,4,5-trisphosphate (IP3) receptor immunopurified from rat cerebellar membranes in vitro and in rat cerebellar slices in situ. The isolated IP3 receptor protein was phosphorylated by both cAMP- and cGMP-dependent protein kinases on two distinct sites as determined by thermolytic phosphopeptide mapping, phosphopeptide 1, representing Ser-1589, and phosphopeptide 2, representing Ser-1756 in the rat protein (Ferris, C. D., Cameron, A. M., Bredt, D. S., Huganir, R. L., and Snyder, S. H. (1991) Biochem. Biophys. Res. Commun. 175, 192-198). Phosphopeptide maps show that cAMP-dependent protein kinase (PKA) labeled both sites with the same time course and same stoichiometry, whereas cGMP-dependent protein kinase (PKG) phosphorylated Ser-1756 with a higher velocity and a higher stoichiometry than Ser-1589. Synthetic decapeptides corresponding to the two phosphorylation sites (peptide 1, AARRDSVLAA (Ser-1589), and peptide 2, SGRRESLTSF (Ser-1756)) were used to determine kinetic constants for the phosphorylation by PKG and PKA, and the catalytic efficiencies were in agreement with the results obtained by in vitro phosphorylation of the intact protein. In cerebellar slices prelabeled with [32P]orthophosphate, activation of endogenous kinases by incubation in the presence of cAMP/cGMP analogues and specific inhibitors of PKG and PKA induced in both cases a 3-fold increase in phosphorylation of the IP3 receptor. Thermolytic phosphopeptide mapping of in situ labeled IP3 receptor by PKA showed labeling on the same sites (Ser-1589 and Ser-1756) as in vitro. In contrast to the findings in vitro, PKG preferentially phosphorylated Ser-1589 in situ. Because both PKG and the IP3 receptor are specifically enriched in cerebellar Purkinje cells, PKG may be an important IP3 receptor regulator in vivo.  (+info)

Interplay between the NO pathway and elevated [Ca2+]i enhances ciliary activity in rabbit trachea. (4/1035)

1. Average intracellular calcium concentration ([Ca2+]i) and ciliary beat frequency (CBF) were simultaneously measured in rabbit airway ciliated cells in order to elucidate the molecular events that lead to ciliary activation by purinergic stimulation. 2. Extracellular ATP and extracellular UTP caused a rapid increase in both [Ca2+]i and CBF. These effects were practically abolished by a phospholipase C inhibitor (U-73122) or by suramin. 3. The effects of extracellular ATP were not altered: when protein kinase C (PKC) was inhibited by either GF 109203X or chelerythrine chloride, or when protein kinase A (PKA) was inhibited by RP-adenosine 3', 5'-cyclic monophosphothioate triethylamine (Rp-cAMPS). 4. Activation of PKC by phorbol 12-myristate, 13-acetate (TPA) had little effect on CBF or on [Ca2+]i, while activation of PKA by forskolin or by dibutyryl-cAMP led to a small rise in CBF without affecting [Ca2+]i. 5. Direct activation of protein kinase G (PKG) with dibutyryl-cGMP had a negligible effect on CBF when [Ca2+]i was at basal level. However, dibutyryl-cGMP strongly elevated CBF when [Ca2+]i was elevated either by extracellular ATP or by ionomycin. 6. The findings suggest that the initial rise in [Ca2+]i induced by extracellular ATP activates the NO pathway, thus leading to PKG activation. In the continuous presence of elevated [Ca2+]i the stimulated PKG then induces a robust enhancement in CBF. In parallel, activated PKG plays a central role in Ca2+ influx via a still unidentified mechanism, and thus, through positive feedback, maintains CBF close to its maximal level in the continuous presence of ATP.  (+info)

Involvement of phosphodiesterase-cGMP-PKG pathway in intracellular Ca2+ oscillations in pituitary GH3 cells. (5/1035)

The present study investigates the potential role of the Ca2+-calmodulin-dependent type I phosphodiesterase (PDE)-cGMP-protein kinase G (PKG) pathway in spontaneous [Ca2+]i oscillations in GH3 cells using fura-2 single cell videoimaging. Vinpocetine (2.5-50 microM), a selective inhibitor of type I PDE, induced a concentration-dependent inhibition of spontaneous [Ca2+]i oscillations in these pituitary cells, and at the same time produced an increase of the intracellular cGMP content. The cell permeable cGMP analog N2,2'-O-dibutyryl-cGMP (dB-cGMP) (1 mM) caused a progressive reduction of the frequency and the amplitude of spontaneous [Ca2+]i oscillations when added to the medium. KT5823 (400 nM), a selective inhibitor of cGMP-dependent protein kinase (PKG), produced an increase of baseline [Ca2+]i and the disappearance of spontaneous [Ca2+]i oscillations. When KT5823 was added before vinpocetine, the PKG inhibitor counteracted the [Ca2+]i lowering effect of the cGMP catabolism inhibitor. Finally, the removal of extracellular Ca2+ or the blockade of L-type voltage-sensitive calcium channels (VSCC) by nimodipine produced a decrease of cytosolic cGMP levels. Collectively, the results of the present study suggest that spontaneous [Ca2+]i oscillations in GH3 cells may be regulated by the activity of type I PDE-cGMP-PKG pathway.  (+info)

Cyclic AMP- and cyclic GMP-dependent protein kinases differ in their regulation of cyclic AMP response element-dependent gene transcription. (6/1035)

The ability of cGMP-dependent protein kinases (cGKs) to activate cAMP response element (CRE)-dependent gene transcription was compared with that of cAMP-dependent protein kinases (cAKs). Although both the type Ibeta cGMP-dependent protein kinase (cGKIbeta) and the type II cAMP-dependent protein kinase (cAKII) phosphorylated the cytoplasmic substrate VASP (vasodilator- and A kinase-stimulated phosphoprotein) to a similar extent, cyclic nucleotide regulation of CRE-dependent transcription was at least 10-fold higher in cAKII-transfected cells than in cGKIbeta-transfected cells. Overexpression of each kinase in mammalian cells resulted in a cytoplasmic localization of the unactivated enzyme. As reported previously, the catalytic (C) subunit of cAKII translocated to the nucleus following activation by 8-bromo-cyclic AMP. However, cGKIbeta did not translocate to the nucleus upon activation by 8-bromo-cyclic GMP. Replacement of an autophosphorylated serine (Ser79) of cGKIbeta with an aspartic acid resulted in a mutant kinase with constitutive kinase activity in vitro and in vivo. The cGKIbetaS79D mutant localized to the cytoplasm and was only a weak activator of CRE-dependent gene transcription. However, an amino-terminal deletion mutant of cGKIbeta was found in the nucleus as well as the cytoplasm and was a strong activator of CRE-dependent gene transcription. These data suggest that the inability of cGKs to translocate to the nucleus is responsible for the differential ability of cAKs and cGKs to activate CRE-dependent gene transcription and that nuclear redistribution of cGKs is not required for NO/cGMP regulation of gene transcription.  (+info)

A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression. (7/1035)

High-frequency stimulation (HFS) of corticostriatal glutamatergic fibers induces long-term depression (LTD) of excitatory synaptic potentials recorded from striatal spiny neurons. This form of LTD can be mimicked by zaprinast, a selective inhibitor of cGMP phosphodiesterases (PDEs). Biochemical analysis shows that most of the striatal cGMP PDE activity is calmodulin-dependent and inhibited by zaprinast. The zaprinast-induced LTD occludes further depression by tetanic stimulation and vice versa. Both forms of synaptic plasticity are blocked by intracellular 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase, indicating that an increased cGMP production in the spiny neuron is a key step. Accordingly, intracellular cGMP, activating protein kinase G (PKG), also induces LTD. Nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) and 7-nitroindazole monosodium salt (7-NINA) block LTD induced by either HFS or zaprinast, but not that induced by cGMP. LTD is also induced by the NO donors S-nitroso-N-acetylpenicillamine (SNAP) and hydroxylamine. SNAP-induced LTD occludes further depression by HFS or zaprinast, and it is blocked by intracellular ODQ but not by L-NAME. Intracellular application of PKG inhibitors blocks LTD induced by HFS, zaprinast, and SNAP. Electron microscopy immunocytochemistry shows the presence of NOS-positive terminals of striatal interneurons forming synaptic contacts with dendrites of spiny neurons. These findings represent the first demonstration that the NO/cGMP pathway exerts a feed-forward control on the corticostriatal synaptic plasticity.  (+info)

Nitric oxide regulation of gene transcription via soluble guanylate cyclase and type I cGMP-dependent protein kinase. (8/1035)

Nitric oxide (NO) regulates the expression of multiple genes but in most cases its precise mechanism of action is unclear. We used baby hamster kidney (BHK) cells, which have very low soluble guanylate cyclase and cGMP-dependent protein kinase (G-kinase) activity, and CS-54 arterial smooth muscle cells, which express these two enzymes, to study NO regulation of the human fos promoter. The NO-releasing agent Deta-NONOate (ethanamine-2,2'-(hydroxynitrosohydrazone)bis-) had no effect on a chloramphenicol acetyltransferase (CAT) reporter gene under control of the fos promoter in BHK cells transfected with an empty vector or in cells transfected with a G-kinase Ibeta expression vector. In BHK cells transfected with expression vectors for guanylate cyclase, Deta-NONOate markedly increased the intracellular cGMP concentration and caused a small (2-fold) increase in CAT activity; the increased CAT activity appeared to be from cGMP activation of cAMP-dependent protein kinase. In BHK cells co-transfected with guanylate cyclase and G-kinase expression vectors, CAT activity was increased 5-fold in the absence of Deta-NONOate and 7-fold in the presence of Deta-NONOate. Stimulation of CAT activity in the absence of Deta-NONOate appeared to be largely from endogenous NO since we found that: (i) BHK cells produced high amounts of NO; (ii) CAT activity was partially inhibited by a NO synthase inhibitor; and (iii) the inhibition by the NO synthase inhibitor was reversed by exogenous NO. In CS-54 cells, we found that NO increased fos promoter activity and that the increase was prevented by a guanylate cyclase inhibitor. In summary, we found that NO activates the fos promoter by a guanylate cyclase- and G-kinase-dependent mechanism.  (+info)

*Biological functions of hydrogen sulfide

"Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype". Journal of Vascular Research. 34 (4): 245 ... Lincoln, T. M.; Cornwell, Taylor (March 1990). "cGMP-dependent protein kinase mediates the reduction of Ca2+ by cAMP in ... increased cGMP triggers an increase in protein kinase G (PKG) activity. PKG reduces intracellular Ca2+ in vascular smooth ... "Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent ...

*Gaseous signaling molecules

"Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype". Journal of Vascular Research. 34 (4): 245 ... which is a heterodimeric enzyme with subsequent formation of cyclic-GMP. Cyclic-GMP activates protein kinase G, which causes ... Lincoln, T. M.; Cornwell, Taylor (March 1990). "cGMP-dependent protein kinase mediates the reduction of Ca2+ by cAMP in ... Ethylene is perceived by a family of five transmembrane protein dimers such as the ETR1 protein in Arabidopsis. The gene ...

*PPP1R17

A Purkinje cell substrate of the cyclic GMP-dependent protein kinase". The Journal of Biological Chemistry. 274 (6): 3485-95. ... a possible downstream component of the cGMP-dependent protein kinase cascade in cerebellar Purkinje cells". Proceedings of the ... Hall KU, Collins SP, Gamm DM, Massa E, DePaoli-Roach AA, Uhler MD (Feb 1999). "Phosphorylation-dependent inhibition of protein ... Protein phosphatase 1 regulatory subunit 17 is a protein that in humans is encoded by the PPP1R17 gene. GRCh38: Ensembl release ...

*ITPR1

5-trisphosphate receptor by cyclic GMP-dependent protein kinase". The Journal of Biological Chemistry. 269 (12): 8701-7. PMID ... Hirota J, Ando H, Hamada K, Mikoshiba K (Jun 2003). "Carbonic anhydrase-related protein is a novel binding protein for inositol ... ITPR1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH) GeneReviews/NCBI/NIH/UW entry on ... Inositol 1,4,5-trisphosphate receptor type 1 is a protein that in humans is encoded by the ITPR1 gene. ITPR1 has been shown to ...

*Vasodilator-stimulated phosphoprotein

"The vasodilator-stimulated phosphoprotein is regulated by cyclic GMP-dependent protein kinase during neutrophil spreading". J. ... "Protein phosphorylation regulated by cyclic nucleotide-dependent protein kinases in cell extracts and in intact human ... 2000). "KT5823 inhibits cGMP-dependent protein kinase activity in vitro but not in intact human platelets and rat mesangial ... VASP is regulated by the cyclic nucleotide-dependent kinases PKA and PKG. Vasodilator-stimulated phosphoprotein has been shown ...

*Nicorandil

Vrolix, M; Raeymaekers, L; Wuytack, F; Hofmann, F; Casteels, R (Nov 1, 1988). "Cyclic GMP-dependent protein kinase stimulates ... "Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular ... Nicorandil stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP). cGMP activates protein kinase G (PKG), ... including increased Rho-kinase activity. Increased levels of Rho-kinase inhibit myosin phosphatase activity, leading to ...

*PRKG1

"Localization of the human gene for the type I cyclic GMP-dependent protein kinase to chromosome 10". Cytogenetics and Cell ... of a novel male germ cell-specific cGMP-dependent protein kinase-anchoring protein by cGMP-dependent protein kinase Ialpha". ... 5-trisphosphate receptor by cyclic GMP-dependent protein kinase". The Journal of Biological Chemistry. 269 (12): 8701-7. PMID ... cGMP-dependent protein kinase 1, alpha isozyme is an enzyme that in humans is encoded by the PRKG1 gene. PRKG1 has been shown ...

*Thromboregulation

In vivo phosphorylation of thromboxane by cyclic GMP-dependent protein kinase" (PDF). Journal of the Salk Institute for ... Nitric oxide (NO) stimulates cGMP production and therefore the activation cGMP-dependent protein kinase (G kinase). This kinase ... cAMP, cyclic adenosine monophosphate, phosphorylate messengers via protein kinase A (PKA). These signaling elements include ... Siess, Wolfgang; Eduardo, Lapetina (1990). "Functional relationship between cyclic AMP-dependent protein phosphorylation and ...

*CGMP-dependent protein kinase

EC 2.7.11.12 Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System cGMP-Dependent Protein Kinases at the US ... cGMP-dependent protein kinase or Protein Kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP ... "A crystal structure of the cyclic GMP-dependent protein kinase I{beta} dimerization/docking domain reveals molecular details of ... "Expression of cyclic guanosine monophosphate-dependent protein kinase in metastatic colon carcinoma cells blocks tumor ...

*FHOD1

... is a cyclic GMP-dependent protein kinase I-binding protein and substrate in vascular smooth muscle cells". J. Biol. Chem. 279 ( ... FH1/FH2 domain-containing protein 1 is a protein that in humans is encoded by the FHOD1 gene. This gene encodes a protein which ... The encoded protein has sequence homology to diaphanous and formin proteins within the Formin Homology (FH)1 and FH2 domains. ... It is a predominantly cytoplasmic protein and is expressed in a variety of human cell lines. FHOD1 has been shown to interact ...

*Discovery and development of phosphodiesterase 5 inhibitors

Cyclic GMP binds to the cGMP-dependent protein kinase (PKG1) which phosphorylates several proteins that results in decreased ... cGMP binding proteins and protein kinase G (PKG). The effect on PKG reduces levels of calcium leading to relaxation of smooth ... Their function is to degrade intracellular second messengers such as cyclic adenine monophosphate (cAMP) and cyclic guanosine ... PDEs are enzymes that hydrolyze cyclic adenosine 3,5-monophosphate (cAMP) and cyclic guanosine 3,5-monophospahate (cGMP), which ...

*Min Zhuo

Presynaptically localized cyclic GMP-dependent protein kinase 1 is a key determinant of spinal potentiation and pain ... 10;74(3):517-29 Saywell SA, Babiec WE, Neverova NV, Feldman JL (2010) Protein kinase G-dependent mechanisms modulate ... Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation. Nature 368, 635-639. Zhuo, M., Hu, Y., ... Schultz, C., Kandel, E. R., and Hawkins, R. D. (1994). Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term ...

*Biological functions of nitric oxide

... cyclic GMP) from guanosine triphosphate (GTP). The soluble cGMP activates cyclic nucleotide-dependent protein kinase G (PKG or ... PKG is a kinase that phosphorylates a number of proteins that regulate calcium concentrations and calcium sensitization, ... The neuronal enzyme (NOS-1) and the endothelial isoform (NOS-3) are calcium-dependent and produce low levels of this gas as a ... NO production by eNOS is dependent on calcium-calmodulin and other cofactors. NO diffuses into the smooth muscle cells of the ...

*List of MeSH codes (D12.644)

... cyclic gmp-dependent protein kinases MeSH D12.644.360.200.575 --- protamine kinase MeSH D12.644.360.250 --- cyclin-dependent ... cyclic nucleotide-regulated protein kinases MeSH D12.644.360.200.125 --- cyclic amp-dependent protein kinases MeSH D12.644. ... map kinase kinase kinase 1 MeSH D12.644.360.400.200 --- map kinase kinase kinase 2 MeSH D12.644.360.400.300 --- map kinase ... kinase kinase 3 MeSH D12.644.360.400.400 --- map kinase kinase kinase 4 MeSH D12.644.360.400.500 --- map kinase kinase kinase 5 ...

*Haemodynamic response

... inducing a signaling cascade that results in the activation of cGMP-dependent protein kinase (PKG) and an ultimate decrease in ... In addition to this, it has already been shown that NO stimulates increased cyclic GMP (cGMP) levels in the smooth muscle cells ... When these proteins are active, they turn on SREBP2 which inhibits LRP-1. LRP-1 helps the brain remove amyloid beta. Therefore ... Two proteins are involved in this accumulation of amyloid beta: serum response factor or SRF and myocardin. Together, these 2 ...

*Cyclic nucleotide

... where it stimulates a protein kinase called cyclic AMP-dependent protein kinase. By phosphorylating proteins, cyclic AMP- ... G proteins). The two most well-studied cyclic nucleotides are cyclic AMP (cAMP) and cyclic GMP (cGMP), while cyclic CMP (cCMP) ... Eckly-Michel A, Martin V, Lugnier C (September 1997). "Involvement of cyclic nucleotide-dependent protein kinases in cyclic AMP ... Wolter S, Golombek M, Seifert R (December 2011). "Differential activation of cAMP- and cGMP-dependent protein kinases by cyclic ...

*Cyclic guanosine monophosphate

cGMP is involved in the regulation of some protein-dependent kinases. For example, PKG (protein kinase G) is a dimer consisting ... Numerous cyclic nucleotide phosphodiesterases (PDE) can degrade cGMP by hydrolyzing cGMP into 5'-GMP. PDE 5, -6 and -9 are cGMP ... cyclic monophosphate (8-Br-cGMP) Francis SH, Corbin JD (August 1999). "Cyclic nucleotide-dependent protein kinases: ... Unlike with the activation of some other protein kinases, notably PKA, the PKG is activated but the catalytic and regulatory ...

*8-Bromoguanosine 3',5'-cyclic monophosphate

It acts as an activator of cGMP-dependent protein kinases. 8-Bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) Rapoport, RM ... "Sodium nitroprusside-induced protein phosphorylation in intact rat aorta is mimicked by 8-bromo cyclic GMP" (Free full text). ... 8-Bromoguanosine 3',5'-cyclic monophosphate is a brominated derivative of cyclic guanosine monophosphate (cGMP). ...

*List of MeSH codes (D08)

... beta-adrenergic-receptor kinase MeSH D08.811.913.696.620.682.700.150.150 --- cyclic gmp-dependent protein kinases MeSH D08.811. ... cyclic nucleotide-regulated protein kinases MeSH D08.811.913.696.620.682.700.150.125 --- cyclic amp-dependent protein kinases ... map kinase kinase kinases MeSH D08.811.913.696.620.682.700.559.100 --- map kinase kinase kinase 1 MeSH D08.811.913.696.620.682. ... map kinase kinase kinase 2 MeSH D08.811.913.696.620.682.700.559.300 --- map kinase kinase kinase 3 MeSH D08.811.913.696.620.682 ...

*Biochemical cascade

"Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes". Biology of ... These proteins activate protein tyrosine kinase (PTK) that phosphorylates various proteins important for capacitation and ... Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase) regulates gene transcription through successive kinase ... "Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte". Development. 136 (11): ...

*CREB1

"Synergism between calcium and cyclic GMP in cyclic AMP response element-dependent transcriptional regulation requires ... Shimomura A, Ogawa Y, Kitani T, Fujisawa H, Hagiwara M (Jul 1996). "Calmodulin-dependent protein kinase II potentiates ... The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal ... This protein is a CREB transcription factor that is a member of the leucine zipper family of DNA-binding proteins. This protein ...

*Nitric oxide

... which is a heterodimeric enzyme with subsequent formation of cyclic-GMP. Cyclic-GMP activates protein kinase G, which causes ... In plants, nitric oxide can be produced by any of four routes: (i) L-arginine-dependent nitric oxide synthase, (although the ... ADP ribosylation of proteins, protein sulfhydryl group nitrosylation, and iron regulatory factor activation. ·NO has been ... Hemoglobin is a prominent example of a heme protein that may be modified by ·NO by both pathways: ·NO may attach directly to ...

*Tyrosine hydroxylase

"Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation". ... Roskoski R, Roskoski LM (Jan 1987). "Activation of tyrosine hydroxylase in PC12 cells by the cyclic GMP and cyclic AMP second ... that are phosphorylated by a variety of protein kinases. Ser40 is phosphorylated by the cAMP-dependent protein kinase. Ser19 ( ... is phosphorylated by the calcium-calmodulin-dependent protein kinase. MAPKAPK2 (mitogen-activated-protein kinase-activating ...

*Calcium in biology

... through a protein kinase C-dependent mechanism". Biochem J. 466 (2): 379-390. doi:10.1042/bj20140881. PMID 25422863. Milo, Ron ... Pugh Jr, E. N.; Lamb, T. D. (1990). "Cyclic GMP and calcium: The internal messengers of excitation and adaptation in vertebrate ... Calcium coordination plays an important role in defining the structure and function of proteins. An example a protein with ... Calcium can bind to several different calcium-modulated proteins such as troponin-C (the first one to be identified) and ...

*PDE2A

cGMP-dependent 3',5'-cyclic phosphodiesterase is an enzyme that in humans is encoded by the PDE2A gene. GRCh38: Ensembl release ... Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... Sadhu K, Hensley K, Florio VA, Wolda SL (1999). "Differential expression of the cyclic GMP-stimulated phosphodiesterase PDE2A ... 2009). "Tumor necrosis factor-alpha-dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability". Blood ...

*Placental growth factor

... cyclic AMP and cyclic GMP in human epithelial cells expressing the FLT-1 receptor". Growth Factors. 19 (3): 193-206. doi: ... Placental growth factor is a protein that in humans is encoded by the PGF gene. Placental growth factor (PGF) is a member of ... Serum levels of PGF and sFlt-1 (soluble fms-like tyrosine kinase-1, also known as soluble VEGF receptor-1) are altered in women ... Shibuya M (April 2008). "Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis". BMB Reports ...
This study shows that in vitro exposure to high glucose (i.e., 25 mmol/L) of platelets from healthy subjects reduces the antiaggregating action of aspirin, an effect blunted by the antioxidant agent amifostine. It also shows that high glucose does not affect the ability of aspirin to inhibit thromboxane synthesis but impairs the ability of aspirin to activate the NO/cGMP/PKG pathway. Furthermore, it demonstrates that high glucose per se does not influence platelet aggregation in response to agonists, thromboxane synthesis, and the NO/cGMP/PKG pathway.. Thus, high glucose reduces the antiaggregating properties of aspirin only at very high concentrations; the extent of inhibition, although significant, is modest. In our experimental conditions, we did not observe the dramatic dose-dependent inhibition of platelet sensitivity to aspirin described by other authors (17,19).. Is it possible to translate results obtained in vitro to in vivo conditions? It is interesting to observe that the lack of ...
The expression and phosphorylation state of VASP was investigated in neutrophils during cell adherence. Adhesion is an essential process for neutrophil migration from the peripheral blood to sites of inflammation. During the process of adhesion, neutrophils adhere and spread without any clear stopping point between these two processes. Therefore, it was important to determine whether VASP was phosphorylated in response to signals involved in adhesion and/or spreading. In this report, we demonstrate that VASP is a target for cGK regulation of neutrophil spreading. We showed that VASP was in its dephosphorylated form in retracted round neutrophils and was rapidly phosphorylated by cGK at the onset of cell spreading. Both adherence and the onset of cell spreading induced significant elevations of cGMP in neutrophils. When neutrophils were incubated with 8-Br-cGMP, a direct activator of cGK, cells became more polarized in suspension, and spread more rapidly during adhesion. Our observations that ...
TY - JOUR. T1 - Phosphorylation of tyrosine hydroxylase by cyclic GMP - Dependent protein kinase. AU - Roskoski, R.. AU - Vulliet, Philip R. AU - Glass, D. B.. PY - 1987. Y1 - 1987. N2 - Tyrosine hydroxylase purified from rat pheochromycytoma was phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase catalytic subunit. The extent of activation was correlated with the degree of phosphate incorporated into the enzyme. Comparable stoichiometric ratios (0.6 mol phosphate/mol tyrosine hydroxylase subunit) were obtained at maximal concentrations of either cyclic AMP-dependent or cyclic GMP-dependent protein kinases. The enzymes appeared to mediate the phosphorylation of the same residue based on the observation that incorporation was not increased when both enzymes were present. The major tryptic phosphopeptide obtained from tyrosine hydroxylase phosphorylated by each protein kinase exhibited an identical retention time following ...
In addition to vasodilation, NO/NP/cGMP signaling is involved in the development of vasculoproliferative disorders, such as restenosis and atherosclerosis. The analysis of transgenic mice showed that NO can both promote58-64 and inhibit65-70 pathological vascular remodeling (see review5). This finding could explain why NO-generating drugs have not been reported to limit the progression of atherosclerosis in humans. The opposing actions of NO might depend on the magnitude and spatiotemporal profile of its production in a specific pathophysiological setting and are likely mediated through different cellular and molecular mechanisms. A key process in vascular remodeling is the phenotypic modulation of vascular SMCs from contractile to proliferating/dedifferentiated cells.71 It has been reported that NO and cGMP can both promote72,73 and inhibit74,75 the proliferation of cultured SMCs (see reviews12,76). The reason for these contradictory findings and their (patho)physiological significance is not ...
Clinical malaria is associated with the proliferation of Plasmodium parasites in human erythrocytes. The coordinated processes of parasite egress from and invasion into erythrocytes are rapid and tightly regulated. We have found that the plant-like calcium-dependent protein kinase PfCDPK5, which is expressed in invasive merozoite forms of Plasmodium falciparum, was critical for egress. Parasites deficient in PfCDPK5 arrested as mature schizonts with intact membranes, despite normal maturation of egress proteases and invasion ligands. Merozoites physically released from stalled schizonts were capable of invading new erythrocytes, separating the pathways of egress and invasion. The arrest was downstream of cyclic guanosine monophosphate-dependent protein kinase (PfPKG) function and independent of protease processing. Thus, PfCDPK5 plays an essential role during the blood stage of malaria replication ...
the objective of this investigation was to study the effect of the presence of red blood cells (RBCs) in the plasma layer adjacent to the arteriole wall on coupled nitric oxide (NO) and oxygen (O2) transport using computer simulations and to compare our model predictions with experimental data from the literature.. NO, produced by endothelial cells lining the vessel wall, diffuses both into the vessel lumen and to surrounding tissues. Most endothelium-derived NO is scavenged by hemoglobin in the RBCs in the bloodstream, and only a portion diffuses abluminally. The portion that diffuses into the vessel wall activates soluble guanylate cyclase (sGC), catalyzing the formation of cyclic 3′,5′-guanosine monophosphate and activating cyclic 3′,5′-guanosine monophosphate-dependent protein kinase. This results in a decrease of Ca2+ inside smooth muscle cells and dephosphorylation of contractile proteins, such as myosin light chain, causing relaxation of vascular smooth muscle (8, 24). Generation ...
Cyclic GMP (cGMP) kinase is intimately involved in the regulation of vascular smooth muscle tone. Its tissue concentration was determined in normotensive and hypertensive rats by use of monospecific anti-cGMP kinase antibodies. Hearts of spontaneously hypertensive rats and renovascular (Goldblatt II) hypertensive rats contained half the concentration of cGMP kinase than those of the respective normotensive animals. The increase in blood pressure and the resulting left ventricular hypertrophy were correlated inversely with the left ventricular cGMP kinase concentration. This decrease was specific for the left ventricle and was not observed in other tissues. In addition, the cardiac concentration of cGMP kinase was unchanged in hyperthyroid animals that had comparable left ventricular hypertrophy and mild hypertension. This suggested that in severe renovascular hypertension the decrease in cardiac cGMP kinase concentration is caused by a relative lack of cardiac vessel growth during the ...
We have discovered that PKG activation by either genetic or pharmacological means was sufficient to destabilize a surrogate misfolded protein (GFPu) substrate of the UPS, whereas PKG inhibition stabilizes the GFPu proteins in cultured cardiomyocytes. Moreover, we have also shown that PKG activation by sildenafil treatment significantly decreases myocardial GFPdgn protein levels but displays no discernible effect on GFPdgn mRNA levels in GFPdgn tg mice. These findings suggest that PKG positively regulates the degradation of a misfolded protein by the UPS. We have further tested this postulate in both cultured cardiomyocytes and intact mice that overexpress CryABR120G, a bona fide misfolded protein known to cause human disease.24 We collected compelling evidence that PKG activation by either genetic or pharmacological methods facilitates whereas PKG inhibition by genetic and pharmacological means decreases the UPS-mediated degradation of CryABR120G in cultured NRVMs.. Sildenafil treatment showed ...
cGMP-dependent protein kinases (PKG) exhibit diverse physiological functions in the mammalian system e.g., in vascular and gastrointestinal smooth muscles, in platelets, in kidney, in bone growth, nociception and in the central nervous system. Furthermore, PKG were found in insects and in the malaria parasite Plasmodium falciparum. Two different genes of PKG exist: a) the PKG-I gene that is expressed as cytosolic PKG-Iα or PKG-Iβ isoform, and b) the PKG-II gene, which expresses the membrane associated PKG-II protein. The enzyme kinetics, the localization and the substrates of these PKG enzymes differ utilizing different physiological functions. Various inhibitors of PKG were developed directed against diverse functional regions of the kinase. These inhibitors of PKG have been used to analyse the specific functions of these enzymes. The review article will summarize these different inhibitors regarding their specificity and their present applications in vitro and in vivo. Furthermore, it will be
Previously, our lab showed that low-level nitric oxide (NO) and downstream activation of the cGMP/protein kinase G (PKG) signaling pathway plays a key role in preventing spontaneous apoptosis and stimulating proliferation in many mammalian cells, including neural cells, vascular smooth muscle cells and certain tumor cells (e.g. human ovarian cancer cells). In cancer cells, PKG is hyper-activated, which may contribute to rapid cell proliferation and resistance to chemotherapy. Recently, our lab found that two mesothelioma cell lines (MSTO-211H and NCI-H2452 cells) and two prostate cancer cell lines (PC-3 and DU145 cells) also show dependence on endogenous NO/cGMP/PKG pathway for promoting proliferation and cell survival (contributing to cisplatin-resistance). Pharmacological blocking of either NO-induced cGMP synthesis (using ODQ) or PKG enzymatic activity (using DT-2) in mesothelioma and prostate cancer cells decreases proliferation rate, increases apoptosis and sensitizes cells to cisplatin. ...
Protein kinase G (PKG) is activated by nitric oxide (NO)-induced cGMP binding or alternatively by oxidant-induced interprotein disulfide formation. We found preactivation with cGMP attenuated PKG oxidation. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) blockade of cGMP production increased disulfide PKG to 13±2% and 29±4% of total in aorta and mesenteries, respectively. This was potentially anomalous, because we observed 2.7-fold higher NO levels in aorta than mesenteries; consequently, we had anticipated that ODQ would induce more disulfide in the conduit vessel. ODQ also constricted aorta, whereas it had no effect on mesenteries. Thus, mesenteries, but not aorta, can compensate for loss of NO-cGMP by recruiting disulfide activation of PKG. Mechanistically, this is explained by loss of cGMP allowing disulfide formation in response to basal oxidant production. Why aorta treated with ODQ generated less PKG disulfide that is insufficient to induce vasoconstriction was unclear. One potential ...
Genes can affect natural behavioral variation in different ways. Allelic variation causes alternative behavioral phenotypes, whereas changes in gene expression can influence the initiation of behavior at different ages. We show that the age-related transition by honey bees from hive work to foraging is associated with an increase in the expression of the foraging (for) gene, which encodes a guanosine 3′,5′-monophosphate (cGMP)-dependent protein kinase (PKG). cGMP treatment elevated PKG activity and caused foraging behavior. Previous research showed that allelic differences in PKG expression result in two Drosophila foraging variants. The same gene can thus exert different types of influence on a behavior. ...
Cyclic guanosine 3,5-monophosphate (cGMP)-dependent protein kinase (PKG) activates a signaling pathway that leads to vascular smooth muscle cell relaxation, a process that reduces blood pressure. This enzyme consists of a dimerization domain, autoinhibitory domain, regulatory domain, and catalytic domain1. PKG is activated by cGMP binding to two binding sites of the regulatory domain. In order to study how each of these two binding sites, A and B, contributes to PKG activation, a mutant that knocked out cGMP binding to the B site, PKG Iα E292A, was expressed in Sf9 cells and purified to apparent homogeneity. Despite the presence of this mutation, the affinity for cGMP determined by surface plasmon resonance (SPR) was unchanged. The mutant still displayed cGMP dependent activation. In addition to these cGMP-binding sites, the regulatory domain contains a switch helix motif that provides a place for crosstalk between the PKG protomers2. It is not well known how this motif affects cyclic
Cardiac stress results in several adverse effects, including hypertrophy and pathological remodeling, that lead to heart failure. Activation of the cGMP-dependent kinase PKG1α, which mediates cardiac and vascular function in response to NO and natriuretic peptide signaling, has been shown to suppress detrimental responses to cardiac stress. These beneficial effects have led to the exploration of PKG1α as a potential therapeutic target; however, clinical outcomes have been variable. Taishi Nakamura and colleagues at Johns Hopkins Medical Institutions demonstrate that oxidation of PKG1α in response to cardiac stress contributes to adverse heart remodeling. In patients with ischemic heart failure and rodent heart disease models, PKG1α oxidation was increased compared to controls. In rodent models, expression of a redox-dead form of PKG1α (PKG1αC42S) reduced adverse cardiac remodeling and preserved function in response to cardiac stress. Compared to WT PKG1α, which localized to the cytosol, ...
5 remained unchanged (Figure 2A) as reported (Renden and von Gersdorff, 2007 and Yamashita et al., 2010). However, after loading. Rp-cGMPS (3 μM), endocytic τ0.5 became slower as depolarizing pulses increased to 5-20 ms (Figure 2A). In the presence of PKG inhibitor, calyceal terminals after hearing (Figure 2A) behave like calyces before hearing (Figure 2B), with the endocytic τ0.5 showing see more a positive correlation with the magnitude of exocytosis. Thus, the PKG-dependent endocytic speeding mechanism matures during the second postnatal week when rodents start to hear sound. At the calyx of Held, repetitive stimulation at 1 Hz accelerates endocytosis to a second-order time constant through a Ca2+-dependent mechanism (Wu et al., 2009 and Yamashita et al., 2010). We asked whether PKG might regulate this rapid endocytosis at P13-P14 calyces. During a short train of stimulation (20 ms depolarizing pulses repeated at 1 Hz for 20 s), as exocytic ΔCm summed up to a high level, the endocytic ...
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There is growing evidence for the antitumor effects of cGMP-dependent protein kinase (PKG) in colon cancer cells. We reported recently that ectopically expressed PKG resulted in defective angiogenesis in xenografts, and was associated with reduced levels of vascular-endothelial growth factor (VEGF). In order to better understand the therapeutic potential of this enzyme, the present work has examined the mechanism of VEGF regulation by PKG. In contrast to the SW620 xenografts, PKG had no effect on VEGF expression in SW620 cells grown under standard tissue culture conditions in vitro. However, the increase in VEGF expression observed when the cells were subjected to hypoxic stress was significantly attenuated by PKG at both the mRNA and protein levels. Using luciferase reporter assays, PKG was shown to inhibit hypoxia inducible factor (HIF) transcriptional activity in several colon cancer cell lines, including SW620, HCT116, and HT29. The attenuation of HIF by PKG reflected a more fundamental ...
TY - JOUR. T1 - Identification of cGMP-Dependent protein kinase anchoring proteins (GKAPs). AU - Vo, Ngan. AU - Gettemy, Jessica M.. AU - Coghlan, Vincent M.. PY - 1998/5/29. Y1 - 1998/5/29. N2 - To promote both efficiency and selectivity, many protein kinases and phosphatases are maintained in specific subcellular microenvironments through their association with anchoring proteins. In this study, we describe a new class of proteins, called GKAPS, that specifically bind the Type II cGMP-dependent protein kinase (PKG). GKAPs were detected in rat aorta, brain, and intestine using a protein overlay technique. The PKG binding proteins were distinct from AKAPs, proteins known to bind the cAMP-dependent protein kinase (PKA). Furthermore, a synthetic peptide that blocks association of PKA with AKAPs did not affect the PKG-GKAP interaction. Deletion mutagenesis was used to map the GKAP binding determinants within PKG to the N-terminal regulatory region. While most GKAPs were tissue-specific, a ...
GF ID PRKG1_interact #=GF AC PF15898.5 #=GF DE cGMP-dependent protein kinase interacting domain #=GF AU Eberhardt R;0000-0001-6152-1369 #=GF SE Jackhmmer:A8JNT6 #=GF GA 32.40 32.40; #=GF TC 33.30 32.50; #=GF NC 32.30 32.30; #=GF BM hmmbuild HMM.ann SEED.ann #=GF SM hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq #=GF TP Family #=GF RN [1] #=GF RM 12873707 #=GF RT Dimerization of cGMP-dependent protein kinase 1alpha and the #=GF RT myosin-binding subunit of myosin phosphatase: role of leucine #=GF RT zipper domains. #=GF RA Surks HK, Mendelsohn ME; #=GF RL Cell Signal. 2003;15:937-944. #=GF RN [2] #=GF RM 10567269 #=GF RT Regulation of myosin phosphatase by a specific interaction with #=GF RT cGMP- dependent protein kinase Ialpha. #=GF RA Surks HK, Mochizuki N, Kasai Y, Georgescu SP, Tang KM, Ito M, #=GF RA Lincoln TM, Mendelsohn ME; #=GF RL Science. 1999;286:1583-1587. #=GF DR INTERPRO; IPR031775; #=GF DR SO; 0100021; polypeptide_conserved_region; #=GF CC This domain is found at the C-terminus ...
Aim: To determine whether Ca2+/calcineurin mediated the inhibitory effects of nitric oxide /cGMP-dependent protein kinase (NO/PKG) on the proliferation of vascular smooth muscle cells (VSMC). Methods: Proliferation and viability of primary VSMC from rat aorta were measured using [3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] (MTT) assay and acridine orange and ethidium bromide staining, respectively. Cytosolic Ca2+ was determined by Fluo-3/AM. Calcineurin protein and its activity were assayed using immunoblotting and free inorganic phosphate analysis, respectively. Results: (+/-)-S-nitroso-N-acetylpenicillamine (SNAP) and Sp-8-(4-chlorophenylthio)-guanosine-3′,5′-cyclic monophosphorothioate (Sp-8-pCPT-cGMPS) decreased phenylephrine (PE)-induced proliferation of VSMC by 27.3% and 36.6%, respectively, but Rp-8-[4-chlorophenyl)thio]-guanosine-3′,5′-cyclic monophosphorothioate (Rp-8-pCPT-cGMPS) increased PE-induced proliferation of VSMC. SNAP, Sp-8-pCPT-cGMPS, and ...
Imidazoline compounds have been considered for the treatment of type 2 diabetes. We have now investigated the effects of imidazolines on interleukin (IL)-1beta-induced beta-cell apoptosis and the signal transduction pathways involved. Inhibition of Ca2+ influx into beta-cells by D-600, a blocker of voltage-gated L-type Ca2+ channels, suppressed IL-1beta-induced apoptosis. Our data show that calcineurin, Ca2+/calmodulin-dependent serine/threonine protein phosphatase 2B, is responsible for the effect of Ca2+ on beta-cell apoptosis. We also demonstrate that IL-1beta-mediated apoptosis correlates with expression of inducible nitric oxide synthase (iNOS) and the increase in intracellular production of nitric oxide. An inhibitor of cGMP-dependent protein kinase (PKG), KT5823, suppressed IL-1beta-induced apoptosis, suggesting the involvement of a PKG-dependent pathway in the apoptotic process. One of the major findings in this study is that imidazoline compounds RX871024 and efaroxan, suggested as ...
Stimulation of protein kinase G (PKG) suppresses maladaptive cardiac hypertrophy in part by blunting signaling cascades such as calcineurin/NFAT (Cn) and calcium-calmodulin dependent kinase II (CamKII). Here we report PKG stimulation also enhances autophagy as an anti-hypertrophic mechanism, identify a novel phosphorylation target for this effect, and show this signaling is blunted when PKG becomes oxidized at cysteine 42 (C42). Mice with knock-in expression of mutant PKG (C42S) or littermate controls were subjected to pressure-overload. C42S mice were protected, with reduced hypertrophy and fibrosis, improved function, and blunted Cn, CamKII, and hypertrophic gene activation. Neonatal rat ventricular myocytes (NRVMs) expressing C42S-PKG exposed to 48hr endothelin-1 (ET1) also displayed less hypertrophic responses. In both C42S mice and NRVMs expressing C42S, autophagic flux was increased over WT, determined by autophagic flux assays, which was associated with inhibited mammalian target of ...
In this study, we identified PKG2 to be a novel K-Ras kinase that phosphorylates K-Ras at Ser181 in response to activation of AMPK. PKG is activated by the AMPK-mediated activation of eNOS, which generates cGMP through NO activation of soluble guanylyl cyclase. Using multiple activators of this pathway to drive K-Ras phosphorylation, we identified two separate consequences of K-Ras phosphorylation. Phospho-K-RasG12V laterally segregates from nonphospho-K-RasG12V to form nanoclusters that acutely retune the K-Ras signal output to enhance both phosphatidylinositol 3-kinase-Akt and Raf-MAPK activation. This is mitigated, however, by a progressive loss of phosphorylated K-Ras from the PM, which subsequently abrogates K-Ras signaling. Thus, AMPK activation can both retune K-Ras signaling and silence it.. The identification of PKG2 among the three expressed isoforms of PKG as the K-Ras kinase is based on several observations. First, knockdown of PKG2 expression was sufficient to completely abolish ...
Two disparate mechanisms have evolved for activating PKG1α; one relies on binding of the second messenger cGMP, the other involves thiol oxidation inducing a disulfide homodimer. In this study, we found that these 2 mechanisms of activating PKG1α are intricately linked with the binding of cGMP preventing oxidation to the disulfide state. The N-terminus of PKG1α, which contains the redox-sensitive cysteine from each monomer of the dimer, have been mapped using NMR.14 This structural information shows that the redox cysteines in PKG1α are in close proximity and orientated to allow the formation of a disulfide bond when oxidants are present. Our observations are consistent with cGMP binding to PKG1α causing an allosteric structural change that reorientates the redox cysteines. This reorientation presumably moves the thiols too far apart or changes their molecular environment such that their pKa is increased to lower their reactivity with oxidants, either of which would attenuate disulfide ...
Dynamic regulation of arterial tone influences blood pressure and flow, and ultimately plays a critical role in cardiovascular health and disease. My research focuses primarily on cellular signaling pathways that impair excitation-contraction coupling in vascular smooth muscle (VSM), thereby reducing contractility and promoting vasodilation. In particular, I am interested in mechanisms that provide constant or tonic modulation of vascular tone by controlling membrane potential, intracellular Ca2+ and the sensitivity of the contractile apparatus to Ca2+. My projects have investigated mechanisms of cyclic nucleotide vasorelaxation, including the pivotal roles of phosphodiesterases and cyclic nucleotide dependent protein kinases. Recent studies using a novel class of cGMP-dependent protein kinase (PKG) inhibitors suggest a critical vasoregulatory role for constitutively active PKG in VSM.. The vascular endothelium (a single layer of cells lining the lumen of the entire vasculature) constantly ...
LNA / Sitter Job Desription|br| |br| Position Summary: The Patient Sitter remains with the patient to provide constant observation and attendance. The Patient Sitter provides
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cAMP- and cGMP-dependent protein kinases (cAPK and cGPK). Both types of kinases contains two tandem copies of the cyclic nucleotide-binding domain. The cAPKs are composed of two different subunits: a catalytic chain and a regulatory chain which contains both copies of the domain. The cGPKs are single chain enzymes that include the two copies of the domain in their N- terminal section. The nucleotide specificity of cAPK and cGPK is due to an amino acid in the conserved region of β-barrel 7: a threonine that is invariant in cGPK is an alanine in most cAPK ...
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The best Calcium pet sitters are here. Find the perfect pet sitter in Calcium, NY for your furry friends. Start searching for petting sitting, free.
Its important to have someone you trust care for your pet while youre away. Keeping your pet at home in the care of a pet sitter will spare your pet the stress and health risks associated with boarding facilities. A pet sitter will not only feed and play with your pet but also water plants, bring in the mail, and take out the trash. Some sitters may also perform grooming or behavior training. A pet sitter can help your home appear to be lived in, which can deter burglars. If you dont have a neighbor, friend, or relative who can care for your pet when youre away, consider hiring a professional pet sitter. Knowing that your pet is being cared for by a professional pet sitter can add to your peace of mind while youre away.. Read More ...
Its important to have someone you trust care for your pet while youre away. Keeping your pet at home in the care of a pet sitter will spare your pet the stress and health risks associated with boarding facilities. A pet sitter will not only feed and play with your pet but also water plants, bring in the mail, and take out the trash. Some sitters may also perform grooming or behavior training. A pet sitter can help your home appear to be lived in, which can deter burglars. If you dont have a neighbor, friend, or relative who can care for your pet when youre away, consider hiring a professional pet sitter. Knowing that your pet is being cared for by a professional pet sitter can add to your peace of mind while youre away.. Read More ...
Its important to have someone you trust care for your pet while youre away. Keeping your pet at home in the care of a pet sitter will spare your pet the stress and health risks associated with boarding facilities. A pet sitter will not only feed and play with your pet but also water plants, bring in the mail, and take out the trash. Some sitters may also perform grooming or behavior training. A pet sitter can help your home appear to be lived in, which can deter burglars. If you dont have a neighbor, friend, or relative who can care for your pet when youre away, consider hiring a professional pet sitter. Knowing that your pet is being cared for by a professional pet sitter can add to your peace of mind while youre away.. Read More ...
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id":"36166","bid":"92228","uid":"0","title":"Pocatellos Professional Pet Sitters","username":"PokyPetSitters","rating":"5","pros":"Your pet stays in the comfort of their own home","cons":".","description":"www.pokypetsitters.com\r\n\r\nat your Bark & Call: In home sitting - Your pet stays in the comfort of their own home. We come to you.\r\n\r\nGotta Go?: Mid-day walks\r\n\r\n\r\nExperienced pet sitter since 2004. \r\n\r\nInsured.\r\n\r\nMember of NAPPS and PSI.","date_added":"1277779680","date_modified":null,"is_external":"1","external_site_name":"zootoo","external_site_url":null,"external_user_profile":null,"status":"1 ...
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Where are U? Linda ---------------------------------------------------------- for HELP or to subscribe/unsubscribe, contact: [email protected] ...
So dd has been doing so great with going potty in the big toilet lately. As far as I know she was going on her own at the sitters house (we have stopped...
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Histamines are present in many foods, especially those that have been aged. Foods with the highest histamine levels are aged cheeses, yogurt, sour cream, meats, salami, bacon, wine, sauerkraut, pickles, soy sauce, and vinegar. However, they are also found in some fresh fruits and vegetables like spinach, tomatoes, papaya, pineapple, strawberries, eggplant, and citrus fruits.…
Histamines are present in many foods, especially those that have been aged. Foods with the highest histamine levels are aged cheeses, yogurt, sour cream, meats, salami, bacon, wine, sauerkraut, pickles, soy sauce, and vinegar. However, they are also found in some fresh fruits and vegetables like spinach, tomatoes, papaya, pineapple, strawberries, eggplant, and citrus fruits.…
Background-The endocrine balance between atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone system is critical for the maintenance of arterial blood pressure and volume homeostasis. This study investigated whether a cardiac imbalance between ANP and aldosterone, towards increased mineralcorticoid receptor (MR) signaling, contributes to adverse left ventricular (LV) remodeling in response to pressure overload. Methods and Results-We used the MR-selective antagonist eplerenone to test the role of MRs in mediating pressure overload-induced dilatative cardiomyopathy of mice with abolished local, cardiac ANP activity. In response to 21-days of transverse aortic constriction (TAC), mice with cardiomyocyte-restricted inactivation (KO) of the ANP receptor (guanylyl cyclase (GC)-A) or the downstream cGMP-dependent protein kinase I (cGKI) developed enhanced LV hypertrophy and fibrosis together with contractile dysfunction. Treatment with eplerenone (100 mg/kg/day) attenuated LV ...
Background: Hemostasis is a critical and active function of the blood mediated by platelets. Therefore, the prevention of pathological platelet aggregation is of great importance as well as of pharmaceutical and medical interest. Endogenous platelet inhibition is predominantly based on cyclic nucleotides (cAMP, cGMP) elevation and subsequent cyclic nucleotide-dependent protein kinase (PKA, PKG) activation. In turn, platelet phosphodiesterases (PDEs) and protein phosphatases counterbalance their activity. This main inhibitory pathway in human platelets is crucial for countervailing unwanted platelet activation. Consequently, the regulators of cyclic nucleotide signaling are of particular interest to pharmacology and therapeutics of atherothrombosis. Modeling of pharmacodynamics allows understanding this intricate signaling and supports the precise description of these pivotal targets for pharmacological modulation. Results: We modeled dynamically concentration-dependent responses of pathway ...
In the present study, we have shown that YC-1 induced an antiproliferative effect in HCC cells in a concentration-dependent manner. YC-1 also inhibited DNA synthesis in HA22T cells and blocked the G1-S transition of the cell cycle. It is well known that elevation of the cGMP levels can be achieved by YC-1 through direct activation of sGC (Wu et al., 1995) and by inhibition of phosphodiesterase activity (Galle et al., 1999). Nevertheless, YC-1-mediated responses through a cGMP-independent pathway have also been described before (Ferrero and Torres, 2001; Hwang et al., 2003). In our study, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (a selective sGC inhibitor) and KT-5823 (a selective inhibitor of cGMP-dependent protein kinase) did not prevent the YC-1-induced antiproliferative effect, nor did YC-1 increase cGMP formation in HA22T cells. These results suggest that YC-1-induced inhibition of HA22T proliferation occurs through a cGMP-independent signaling pathway. Soluble guanylyl cyclase is a ...
The study published in Nature Medicine, led by Dr Philip Eaton from Kings, and co-funded by the British Heart Foundation (BHF) and Medical Research Council (MRC), showed that oxidants steal electrons from other molecules in a chemical reaction which helps prevent high blood pressure.. The researchers looked at mice carrying a mutation to a protein, called protein kinase G, which helps keep blood pressure under control. They showed that mice with the mutation developed high blood pressure because their protein kinase G was unable to sense oxidants normally. The mutation is very small, only enough to change one atom in protein kinase G, but it is enough to stop it from working.. Dr Philip Eaton, Professor of Cardiovascular Biochemistry at Kings commented: Our work adds to a shift in how the scientific community views oxidants; there is a growing body of evidence they are produced in healthy cells where they play crucial regulatory functions. Now we have shown the importance of oxidants for ...
See 2019 Acura MDX 3.5L Advance and Entertainment Pkgs 4dr SH-AWD Safety and Crash Test Ratings at Car.com. We have data from both the NHTSA and the IIHS.
Here I describe a study of comparative behavioral genetics of a complex behavioral phenotype that is affected by a gene encoding a cGMP-dependent protein kinase (PKG, foraging). I accomplish this by using a traditional ...
The homology-based models of binding domains in CNG channel depend heavily on the template structure of CAP and are sensitive to 1) the uncertainties inherent in defining energy terms and 2) the assumptions regarding the intricate and extensive couplings between neighboring side chains. It is therefore important to test these models, particularly the explicit predictions of prominent interactions. In one such experimental test, Thr560 in Brcng was investigated through site-directed mutagenesis and expression (Altenhofen et al., 1991). It was found that Thr560 determined the selectivity of cGMP over cAMP, a finding consistent with the interpretation of an earlier structure model of cGMP-dependent protein kinase (Weber et al., 1989). In another study, Tibbs et al. found that the highly conserved Arg559, one residue upstream of Thr560, formed a favorable ionic bond with cGMP (Tibbs et al., 1998), again agreeing with previous models. The largest shifts caused by amino acid substitutions amounted to ...
Its important to have someone you trust care for your pet while youre away. Keeping your pet at home in the care of a pet sitter will spare your pet the stress and health risks associated with boarding facilities. A pet sitter will not only feed and play with your pet but also water plants, bring in the mail, and take out the trash. Some sitters may also perform grooming or behavior training. A pet sitter can help your home appear to be lived in, which can deter burglars. If you dont have a neighbor, friend, or relative who can care for your pet when youre away, consider hiring a professional pet sitter. Knowing that your pet is being cared for by a professional pet sitter can add to your peace of mind while youre away.. Read More ...
Turn a passion for pets into a career as a dog sitter. Fetch! Pet Care gives the 4-1-1 on how to become a sitter and spend more time with your furry pals.
Author: mmaslano Update of /cvs/pkgs/rpms/perl-POE-Component-Child/devel In directory cvs01.phx2.fedoraproject.org:/tmp/cvs-serv13892 Modified Files: perl-POE-Component-Child.spec Log Message: - Mass rebuild with perl-5.12.0 Index: perl-POE-Component-Child.spec =================================================================== RCS file: /cvs/pkgs/rpms/perl-POE-Component-Child/devel/perl-POE-Component-Child.spec,v retrieving revision 1.8 retrieving revision 1.9 diff -u -p -r1.8 -r1.9 --- perl-POE-Component-Child.spec 7 Dec 2009 09:30:29 -0000 1.8 +++ perl-POE-Component-Child.spec 4 May 2010 21:04:18 -0000 1.9 @@ -1,6 +1,6 @@ Name: perl-POE-Component-Child Version: 1.39 -Release: 7%{?dist} +Release: 8%{?dist} Summary: Child management component for POE Group: Development/Libraries @@ -53,6 +53,9 @@ rm -rf %{buildroot} %changelog +* Tue May 04 2010 Marcela Maslanova ,mmaslano at redhat.com, - 1.39-8 +- Mass rebuild with perl-5.12.0 + * Mon Dec 7 2009 Stepan Kasal ,skasal at redhat.com, - 1.39-7 - ...
Author: rdieter Update of /cvs/pkgs/rpms/kdebase-workspace/devel In directory cvs01.phx2.fedoraproject.org:/tmp/cvs-serv14914 Modified Files: kdebase-workspace.spec Log Message: omit plymouth/kdm patches for now (working on it) Index: kdebase-workspace.spec =================================================================== RCS file: /cvs/pkgs/rpms/kdebase-workspace/devel/kdebase-workspace.spec,v retrieving revision 1.414 retrieving revision 1.415 diff -u -p -r1.414 -r1.415 --- kdebase-workspace.spec 7 Jul 2010 17:27:35 -0000 1.414 +++ kdebase-workspace.spec 7 Jul 2010 18:24:04 -0000 1.415 @@ -2,11 +2,12 @@ %define polkit_1 1 #define polkit_09 1 -%if 0%{?fedora} , 12 -%define plymouth_hack_ping 1 -%else -%define plymouth_hack_spool 1 -%endif +## FIXME/TODO : Rex is working on fixing these +#if 0%{?fedora} , 12 +#define plymouth_hack_ping 1 +#else +#define plymouth_hack_spool 1 +#endif %{!?python_sitearch:%global python_sitearch %(%{__python} -c from distutils.sysconfig import get_python_lib; ...
As your baby continues to develop during 4-6 months , pay attention to developmental cues which signal she is ready for solids and take the steps needed in preparing for a Supported Sitter nutritious meal plan.
Sitter Miles dummy features lifecast arms and head, all with poseable armature wire. Body is a canvas dummy with armature wire for poseable waist, hips and knee
Please note: This does not include the valves. If you are purchasing this for use on the Little Anne Manikin, you will also need the Valves Complete, 2pkgs item # 020310 (pk of 50).. You can also purchase Little Anne Airways COMPLETE, which is part # 020300 (pk of 24) or 020301 (pk of 96).. ...
1 mm X 150 mm, 1 mm X 50 mm, pkg, Pkg, pkg, Pkg, pkg, 6 mm X 100 mm, 6 mm X 150 mm, 6 mm X 250 mm, 1, 8 mm X 300 mm, 3 mm X 100 mm, 9 mm X 20 mm, 6 x 150 mm, 300 µm X 50 mm, 4 µm, 8 x 300 mm, 5 µm, 7 µm, 6 x 10 mm (THF), 4, 10 µm, 2, 5, 7
Tips and resources for buying your next horse Whether you are green and looking to buy your first horse, or a seasoned professional looking for a new challenge, you must prepare yourself prior to visiting a potential new partner. These lists will help keep you from being swept away by the sight of the equine of your dreams when that Horse For Sale! ad calls out your name.
This is another pipe sent to me by a fellow member of the Canadian Cigar Forum. As with the Sabra Apple, the pipe belonged to his grandfather and was in need of a bit of work before the owner could use it. I took this series of pics when the pipe arrived. Overall it appeared…
Hello Im Stefanie and I live in Bethpage TN . I moved our here from northern California. I grew up on 100 acres and grew up with all kinds of animals. Looking forward to ease your mind about leaving and if your babies are OK I promise to treat them like they are my own 615-268-...
id":"6416","bid":"22067","uid":"0","title":"good","username":"ladyheck","rating":"4","pros":"needed","cons":"none","description":" I think this is where we had our Dog,When we visited there. Dunkin,our pup,sure liked them!","date_added":"1206460769","date_modified":null,"is_external":"1","external_site_name":"zootoo","external_site_url":null,"external_user_profile":null,"status":"1 ...
How do you keep tabs on a skittish cat who wont come out for your pet sitter? With a pint-sized, motion-activated camera, of course. ...
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Casein Kinase Ialpha: A casein kinase I isoenzyme that plays a role in intracellular signaling pathways including the CELL CYCLE, membrane trafficking, and RNA processing. In DROSOPHILA casein kinase Ialpha has been in regulation of Hedghog and Wingless signaling pathways. Multiple isoforms of casein kinase Ialpha exist and are due ALTERNATIVE SPLICING.
An antiserum against the catalytic subunit C of cyclic AMP-dependent protein kinase, isolated from bovine heart type II protein kinase, was produced in rabbits. Reaction of the catalytic subunit with antiserum and separation of the immunoglobulin G fraction by Protein A-Sepharose quantitatively removed the enzyme from solutions. Comparative immunotitration of protein kinases showed that the amount of antiserum required to eliminate 50% of the enzymic activity was identical for pure catalytic subunit, and for holoenzymes type I and type II. The reactivity of the holoenzymes with the antiserum was identical in the absence or the presence of dissociating concentrations of cyclic AMP. Most of the holoenzyme (type II) remains intact when bound to the antibodies as shown by quantification of the regulatory subunit in the supernatant of the immunoprecipitate. Titration with the antibodies also revealed the presence of a cyclic AMP-independent histone kinase in bovine heart protein kinase I preparations ...
Previous studies showed that flow activates TRPV4 in TRPV4-overexpressing HEK cells.8 However, the detailed activation mechanism remains obscure. In the present study, we found that coexpression of TRPC1 with TRPV4 altered the decay kinetics of flow-induced [Ca2+]i increase and 4α-PDD-stimulated whole-cell current; it also enabled the [Ca2+]i transient to be negatively regulated by PKG. Interfering TRPC1 with T1E3 or TRPC1Δ567-793 diminished the [Ca2+]i increase in TRPV4-C1-coexpressing HEK cells. Coimmunoprecipitation, FRET, and subcellular colocalization experiments demonstrated a close physical association of TRPV4 with TRPC1. These data strongly suggest a physical interaction of TRPC1 with TRPV4 and an important functional role of this interaction in flow-induced Ca2+ influx.. TRPV4 is abundantly expressed in vascular endothelial cells,19 and plays a key role in flow-induced endothelial Ca2+ influx and subsequent vascular dilation.2,3 Interestingly, flow-induced [Ca2+]i transient in native ...
The generation of nitric oxide (NO) in penile erectile tissue and the subsequent elevation of cyclic GMP (cGMP) levels are important for normal penile erection. Current treatments of erectile dysfunction elevate either cGMP levels by blocking cGMP degrading phosphodiesterase 5 or cyclic AMP (cAMP) levels by intrapenile injection of prostaglandin E1. The molecular target or targets of cGMP in erectile tissue and the role of cAMP for normal penile erection are not known. Herein, we report that mice lacking cGMP-dependent kinase I (cGKI) have a very low ability to reproduce and that their corpora cavernosa fail to relax on activation of the NO/cGMP signaling cascade. Elevation of cAMP by forskolin, however, induces similar relaxation in normal and cGKI-null corpus cavernosum. In addition, sperm derived from cGKI-null mice is normal, can undergo acrosomal reactions, and can efficiently fertilize eggs. Altogether, these data identify cGKI as the downstream target of cGMP in erectile tissue and ...
The generation of nitric oxide (NO) in penile erectile tissue and the subsequent elevation of cyclic GMP (cGMP) levels are important for normal penile erection. Current treatments of erectile dysfunction elevate either cGMP levels by blocking cGMP degrading phosphodiesterase 5 or cyclic AMP (cAMP) levels by intrapenile injection of prostaglandin E1. The molecular target or targets of cGMP in erectile tissue and the role of cAMP for normal penile erection are not known. Herein, we report that mice lacking cGMP-dependent kinase I (cGKI) have a very low ability to reproduce and that their corpora cavernosa fail to relax on activation of the NO/cGMP signaling cascade. Elevation of cAMP by forskolin, however, induces similar relaxation in normal and cGKI-null corpus cavernosum. In addition, sperm derived from cGKI-null mice is normal, can undergo acrosomal reactions, and can efficiently fertilize eggs. Altogether, these data identify cGKI as the downstream target of cGMP in erectile tissue and ...
CL54950100 - 3-Azabicyclo(3.3.1)nonane, 9-alpha-methoxy-3-methyl-9-beta-phenyl-, citrate (1:1) - Searchable synonyms, formulas, resource links, and other chemical information.
The direct targets of extremely low and microwave frequency range electromagnetic fields (EMFs) in producing non-thermal effects have not been clearly established. However, studies in the literature, reviewed here, provide substantial support for such direct targets. Twenty-three studies have shown that voltage-gated calcium channels (VGCCs) produce these and other EMF effects, such that the L-type or other VGCC blockers block or greatly lower diverse EMF effects. Furthermore, the voltage-gated properties of these channels may provide biophysically plausible mechanisms for EMF biological effects. Downstream responses of such EMF exposures may be mediated through Ca(2+) /calmodulin stimulation of nitric oxide synthesis. Potentially, physiological/therapeutic responses may be largely as a result of nitric oxide-cGMP-protein kinase G pathway stimulation. A well-studied example of such an apparent therapeutic response, EMF stimulation of bone growth, appears to work along this pathway. However, ...
Earlier studies indicate that G₁ mediates enhanced renovascular responses to Ang II in SHR. The potentiation of Ang II by the G₁ pathway is blocked by pretreatment with pertussis toxin, an inhibitor of G₁. The G₁ pathway is also activated by receptors for PP-fold peptides; NPY, PYY, and PYY₃₋₃₆. Therefore, we hypothesize that in genetically predisposed models of hypertension PP-fold peptides augment renovascular responses to endogenous Ang II. Our study shows that LPNPY, an analogue of NPY selective for the Y₁ receptor, potentiates Ang II responses in SHR, but not WKY, kidneys in vitro. LPNPYfs ability to potentiate Ang II renovascular responses is dependent on the Y₁ receptor and an intact G₁ pathway. The renal expression of Y₁ receptors is similar in SHR versus WKY. Our study also demonstrates that PYY₃₋₃₆, selective for the Y₂ receptor, potentiates renovascular responses to Ang II in SHR, but not WKY, in vitro. PYY₃₋₃₆ is dependent on an intact ...
The heart initially compensates for hypertension-mediated pressure overload by enhancing its contractile force and developing hypertrophy without dilation. Gq protein-coupled receptor pathways become activated and can depress function, leading to cardiac failure. Initial adaptation mechanisms to reduce cardiac damage during such stimulation remain largely unknown. Here we have shown that this initial adaptation requires regulator of G protein signaling 2 (RGS2). Mice lacking RGS2 had a normal basal cardiac phenotype, yet responded rapidly to pressure overload, with increased myocardial Gq signaling, marked cardiac hypertrophy and failure, and early mortality. Swimming exercise, which is not accompanied by Gq activation, induced a normal cardiac response, while Rgs2 deletion in Gαq-overexpressing hearts exacerbated hypertrophy and dilation. In vascular smooth muscle, RGS2 is activated by cGMP-dependent protein kinase (PKG), suppressing Gq-stimulated vascular contraction. In normal mice, but not ...
Its important to have someone you trust care for your pet while youre away. Keeping your pet at home in the care of a pet sitter will spare your pet the stress and health risks associated with boarding facilities. A pet sitter will not only feed and play with your pet but also water plants, bring in the mail, and take out the trash. Some sitters may also perform grooming or behavior training. A pet sitter can help your home appear to be lived in, which can deter burglars. If you dont have a neighbor, friend, or relative who can care for your pet when youre away, consider hiring a professional pet sitter. Knowing that your pet is being cared for by a professional pet sitter can add to your peace of mind while youre away.. Read More ...
Hi my name is Anna and I am currently trying to save up money for a new place. So i figured why not doing it by doing what I love. I love animals and kids. I have lots of experience with animals, and also with kids. I have worked with kids ranging from newborn to teenagers. I also have experience with special need children. I have experience with animals ranging from rats to dogs haha. My rates are $2.50 an hour per child or $3.00 an hour for pets. If you need a babysitter or dog sitter...
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Dogs and pet sitting - PetSitter.com provides access to the best pet sitters in Victoria, British Columbia and all across the USA and Canada. Visit us to find the most qualified pet sitter for your pet !
Author: rjones Update of /cvs/pkgs/rpms/ocaml-bisect/devel In directory cvs1.fedora.phx.redhat.com:/tmp/cvs-serv2792 Modified Files: ocaml-bisect.spec Log Message: Rebuild for OCaml 3.11.1 Index: ocaml-bisect.spec =================================================================== RCS file: /cvs/pkgs/rpms/ocaml-bisect/devel/ocaml-bisect.spec,v retrieving revision 1.5 retrieving revision 1.6 diff -u -p -r1.5 -r1.6 --- ocaml-bisect.spec 16 Apr 2009 09:06:01 -0000 1.5 +++ ocaml-bisect.spec 23 May 2009 08:53:49 -0000 1.6 @@ -6,7 +6,7 @@ Name: ocaml-bisect Version: %{mainversion} -Release: 0.4.%{subversion}%{?dist} +Release: 0.5.%{subversion}%{?dist} Summary: OCaml code coverage tool Group: Development/Libraries @@ -97,6 +97,9 @@ rm -rf $RPM_BUILD_ROOT %changelog +* Sat May 23 2009 Richard W.M. Jones ,rjones redhat com, - 1.0-0.5.alpha +- Rebuild for OCaml 3.11.1 + * Thu Apr 16 2009 S390x secondary arch maintainer ,fedora-s390x lists fedoraproject org, - ExcludeArch sparc64, s390, s390x as we dont ...
Author: rjones Update of /cvs/pkgs/rpms/ocaml-reins/devel In directory cvs1.fedora.phx.redhat.com:/tmp/cvs-serv31267 Modified Files: ocaml-reins.spec Log Message: Rebuild for OCaml 3.11.1 Index: ocaml-reins.spec =================================================================== RCS file: /cvs/pkgs/rpms/ocaml-reins/devel/ocaml-reins.spec,v retrieving revision 1.4 retrieving revision 1.5 diff -u -p -r1.4 -r1.5 --- ocaml-reins.spec 16 Apr 2009 09:06:15 -0000 1.4 +++ ocaml-reins.spec 23 May 2009 11:19:19 -0000 1.5 @@ -3,7 +3,7 @@ Name: ocaml-reins Version: 0.1a -Release: 4%{?dist} +Release: 5%{?dist} Summary: Library of OCaml persistent data structures Group: Development/Libraries @@ -128,6 +128,9 @@ rm -rf $RPM_BUILD_ROOT %changelog +* Sat May 23 2009 Richard W.M. Jones ,rjones redhat com, - 0.1a-5 +- Rebuild for OCaml 3.11.1 + * Thu Apr 16 2009 S390x secondary arch maintainer ,fedora-s390x lists fedoraproject org, - ExcludeArch sparc64, s390, s390x as we dont have OCaml on those archs (added ...
Looking for a pet sitter or dog walker in the area of North Pittsburgh? Fetch! Pet Care can do all the legwork to find a bonded, insured, and loving match for your pet today.
Previous house sitting experience includes live in doggie au pair. I have worked for a number of families looking after their dogs and cats, and in one instance a large menagerie of exotic birds, 12 total, while they traveled. I have been flown to other cities after certain clients moved, but still felt I was the best person to look after their dog and home while they traveled. References upon request.
And then sometimes it feels like this is the only choice I can make, really. Remember our sitter that we had coming once/week? Well, that isnt happening anymore. Last week (Saturday), we left for an hour and Ginger started screaming and would not stop. She did not want us to leave, and spent the whole time in the corner sobbing. Our sitter called us, and I couldnt quite understand her (she was speaking Spanish very rapidly)...so I raced home. The sitter was so shell-shocked that I dont think she wants to come back. Maybe were not enough hours to make it worth her while, I dont know. But again, so even if I wanted to go back to work...how realistic is that? I cant have Ginger sobbing in the corner every day. I know she would get over it, but it still breaks my heart ...
Find a loving, insured cat sitter near you. Our cat sitters offer a drop-in or house sitting service from £8/visit. All cat sitters are vetted by CatInAFlat.
(24-04-2014 04:08 PM)Hobbitgirl Wrote: Hitchens may have been a bulldog, But he was an intelligent bulldog with class. Haha. sorry I lack class and a lot more knowledge. Im just a little rant-esque t
Det övergripande syftet med denna uppsats har varit att genom en studie på charterarrangören Ving, som har kompletterat sin nuvarande tjänst genom att erbjuda denna på Internet, undersöka upplevd tjänstekvalitet samt hur den nya tjänsten påverkar kundens relation till företaget.. ...
3. This porch is made for sitting: With the abundance of craftsman homes in the Pasadena area, theres no shortage of front porches. But I cant remember the last time I saw someone actually sitting on one of them. Not so in Ravenswood. I must have seen (and waved to) more than a dozen porch sitters. They were no doubt drinking "sweet tea," the common name for iced tea with sugar ...
center, or a baby sitter in facilities either on or off the employers premises. 2The percentile groupings are based on the average wage for each occupation surveyed, which may include workers both above ...
TY - JOUR. T1 - Phosphorylation of cardiac troponin by guanosine 3. T2 - 5-monophosphate-dependent protein kinase. AU - Blumenthal, D. K.. AU - Stull, J. T.. AU - Gill, G. N.. PY - 1978. Y1 - 1978. N2 - Homogeneous cGMP-dependent protein kinase catalyzes the rapid incorporation of phosphate, specifically into the inhibitory subunit of purified cardiac troponin with a maximal incorporation of 1 mol of phosphate/mol of troponin. When troponin was incubated in the presence of both cGMP- and cAMP-dependent protein kinases, a maximal incorporation of 1 mol of phosphate/mol of troponin was observed which suggested phosphorylation of the same site by the two kinases. Both cyclic nucleotide-dependent kinases had similar K(m) values for troponin, but the V(max) value for the phosphorylation reaction catalyzed by cAMP-dependent protein kinase was 12-fold greater than the value obtained for cGMP-dependent protein kinase.. AB - Homogeneous cGMP-dependent protein kinase catalyzes the rapid incorporation of ...
We have previously shown that the protein kinase inhibitor β (PKIβ) form of the cAMP-dependent protein kinase inhibitor exists in multiple isoforms, some of which are specific inhibitors of the cAMP-dependent protein kinase, whereas others also inhibit the cGMP-dependent enzyme [Kumar, Van Patten and Walsh (1997), J. Biol. Chem. 272, 20011-20020]. We have now demonstrated that the switch from a cAMP-dependent protein kinase (PKA)-specific inhibitor to one with dual specificity arises as a consequence of alternate gene splicing. We have confirmed using bacterially produced pure protein that a single inhibitor species has dual specificity for both PKA and cGMP-dependent protein kinase (PKG), inhibiting each with very high and closely similar inhibitory potencies. The gene splicing converted a protein with 70 amino acids into one of 109 amino acids, and did not change the inhibitory potency to PKA, but changed it from a protein that had no detectable PKG inhibitory activity to one that now ...
We used an autoimmune serum from a patient with discoid lupus erythematosus to clone a cDNA of 2808 base pairs. Its open reading frame of 2079 base pairs encodes a predicted polypeptide of 693 amino acids named CDA1 (cell division autoantigen-1). CDA1 has a predicted molecular mass of 79,430 Daltons and a pI of 4.26. The size of the cDNA is consistent with its estimated mRNA size. CDA1 comprises an N-terminal proline-rich domain, a central basic domain, and a C-terminal bipartite acidic domain. It has four putative nuclear localization signals and potential sites for phosphorylation by cAMP and cGMP-dependent kinases, protein kinase C, thymidine kinase, casein kinase II, and cyclin-dependent kinases (CDKs). CDA1 is phosphorylated in HeLa cells and by cyclin D1/CDK4, cyclin A/CDK2, and cyclin B/CDK1 in vitro. Its basic and acidic domains contain regions homologous to almost the entire human leukemia-associated SET protein. The same basic region is also homologous to nucleosome assembly proteins, testis
The PhD work presented here is to delineate the roles of Relish and cGMP-dependent kinases in mechanisms of epithelial stress handling using a genetically tractable epithelium, the Drosophila Malpighian tubule, as an in vivo model for stress sensing and response. Relish, a transcription factor, is the insect orthologue of the mammalian NF-kB. It regulates the insects innate immune pathway and is highly expressed in D. melanogaster tubules. We show that Relish expressed in Malpighian tubules modulates organismal tolerance to osmotic stress caused due to a high salt diet (salt stress). In order to determine the genes that are involved in salt stress tolerance, Affymetrix Drosophila GeneChips (microarrays) were run with RNA isolated from the wild-type and Relish mutant tubules from flies fed either on normal food, or on salt food . The transcriptomic data was analysed to find genes that were dependent and independent of Relish in response to stress. Additionally, the data also revealed that ...
Activation of Ca2+-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca2+ signals (Ca2+ sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries. We report that physiological intraluminal pressure within resistance arteries activated cGMP-dependent protein kinase (PKG) in VSMCs through oxidant-induced formation of an intermolecular disulfide bond between cysteine residues. Oxidant-activated PKG was required to trigger Ca2+ sparks, BK channel activity, and vasodilation in response to pressure. VSMCs from arteries from mice expressing a form of PKG that could not be activated by oxidants showed reduced Ca2+ spark frequency, and arterial preparations from these mice had decreased pressure-induced activation of BK channels. Thus, the absence of oxidative activation of PKG disabled the BK channel-mediated negative feedback ...
TY - JOUR. T1 - Cardiac titin. T2 - A multifunctional giant. AU - Lewinter, Martin M.. AU - Granzier, Hendrikus "Henk". PY - 2010/5/18. Y1 - 2010/5/18. N2 - Titin is responsible for the passive and restoring force of the cardiac sarcomere and makes a major contribution to the diastolic wall stress of the LV, the level of which can be tuned through differential splicing and phosphorylation. PKA and PKG phosphorylation lower stress, and PKC increases it. Changes in titin phosphorylation and titin splicing occur in cardiac disease, in addition to mutations in the titin gene. A host of titin-binding proteins have been discovered that implicate titin as a key player in the organization and development of the sarcomere, in protein turnover, and in sensing mechanical stress. Several stress-sensing signalosomes along the molecule have been discovered, of which only the FHL-based signalosome binds to a spring element (N2B). This N2B-FHL signalosome is ideally situated to sense sarcomere strain and link ...
BioAssay record AID 630202 submitted by ChEMBL: Inhibition of retinal rod CNGA1/CNGB1 expressed in Xenopus laevis oocytes assessed as blockade of cGMP-induced current at +50 mV holding potential by patch-clamp electrophysiology.
Its important to have someone you trust care for your pet while youre away. Keeping your pet at home in the care of a pet sitter will spare your pet the stress and health risks associated with boarding facilities. A pet sitter will not only feed and play with your pet but also water plants, bring in the mail, and take out the trash. Some sitters may also perform grooming or behavior training. A pet sitter can help your home appear to be lived in, which can deter burglars. If you dont have a neighbor, friend, or relative who can care for your pet when youre away, consider hiring a professional pet sitter. Knowing that your pet is being cared for by a professional pet sitter can add to your peace of mind while youre away.. Read More ...
Its important to have someone you trust care for your pet while youre away. Keeping your pet at home in the care of a pet sitter will spare your pet the stress and health risks associated with boarding facilities. A pet sitter will not only feed and play with your pet but also water plants, bring in the mail, and take out the trash. Some sitters may also perform grooming or behavior training. A pet sitter can help your home appear to be lived in, which can deter burglars. If you dont have a neighbor, friend, or relative who can care for your pet when youre away, consider hiring a professional pet sitter. Knowing that your pet is being cared for by a professional pet sitter can add to your peace of mind while youre away.. Read More ...
What I want to talk about today is something that is likely affecting every one of you, and it is only a matter of time before it rears itself as severe pain: hyper lordosis - the sitter disease. I had this for over a year and just now nearly rid of it. Here is a…
Find a babysitter today. Sitters have referenced checked babysitters and childminders in Warwick House. The UKs favourite babysitting service.
Families will be able to identify relatives with mutation, take steps to monitor and treat. A multi-institutional team led by Dianna Milewicz, M.D., Ph.D., of The University of Texas Health Science Center at Houston (UTHealth) has found a recurrent genetic mutation that has been linked to deadly thoracic aortic dissections in family members as young as 17 years of age.. The gene known as PRKG1 makes a protein called cGMP-dependent kinase, type I. The PRKG1 mutation alters the function of the protein and causes the muscle cells in the wall of the aorta to respond incorrectly to pulsatile blood flow from the heart, and the change in this one protein ultimately causes thoracic aortic aneurysm and acute aortic dissection. The mutation was identified in four families, including three in the United States. The majority of the affected family members suffered acute aortic dissections at young ages (17 to 51 years).. "What is unique about this finding is that we identified four unrelated families from ...
Rubber band proteins" can be influenced. Sildenafil inhibits a specific enzyme (phosphodiesterase 5 A), which causes the increased formation of a messenger substance (cGMP). The messenger substance activates the enzyme protein kinase G, which attaches phosphate groups to certain proteins. This so-called phosphorylation causes blood vessels to relax, which was why the "potency pill" Viagra originally came onto the market. The Bochum and Rochester researchers found that the cardiac muscle protein titin is also phosphorylated through the same mechanism. "The titin molecules are similar to rubber bands" explains the Bochum physiologist. "They contribute decisively to the stiffness of the cardiac walls." The activity of the protein kinase G causes titin to relax. This makes the cardiac walls more elastic. The effect occurs within minutes of administering the drug.. ...
With PDEs inactivated by IBMX, we assume that there are two pathways for inhibition of ICa(L) by cGMP/PKG, namely, phosphorylation of the α1c subunit that antagonizes the stimulant effect of cAMP/PKA and/or activation of PP that dephosphorylates the α1c subunit. Can 8-Br-cGMP or CCh suppress Ca2+ current through L-type channels in the presence of ATPγS, which allows kinases to thiophosphorylate substrates that resist phosphatase action? Irreversible suppression by 8-Br-cGMP would indicate that thiophosphorylation of the channel had occurred at a site different from that acted upon by cAMP/PKA (Méry et al., 1991; Sumii and Sperelakis, 1995). Alternatively, failure of 8-Br-cGMP to suppress ICa(L) in ATPγS would indicate that the thiophosphorylated channel was resistant to phosphatase. Our results are consistent with the PP hypothesis for inhibition by cGMP of current through L-type channels in guinea pig ventricular myocytes.. Neurotransmitter regulation of ICa(L) by reversible ...
A comparative analysis on protein kinases encoded in the completely sequenced genomes of two plant species, namely Arabidopsis thaliana and Oryza sativa spp japonica cv. Nipponbare is reported in the current study. We have analysed 836 and 1386 kinases identified from A. thaliana and the $O$. sativa genomes respectively. Their classification into known subfamilies reveals selective expansions of the plant receptor kinase subfamily comprising of Ser/Thr receptor kinases. The presence of calciumdependent kinases, and potential absence of cyclic nucleotide-dependent protein kinase of the type found in other (non-plant) eukaryotes, are other notable features of the two plant kinomes described here. An analysis on domain organisation of each of the protein kinases encoded in the plant genome has been carried out. Uncommon composition of functional domains like nuclear translocation factor domain, redox sensor domain (PAS), ACT and lectin domains are observed in few protein kinases shared between the ...
Circadian entrainment is a fundamental property by which the period of the internal biological clock is entrained by recurring exogenous signals, such that the organisms endocrine and behavioral rhythms are synchronized to environmental cues. In mammals, a master clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and may synchronize circadian oscillators in peripheral tissues. Light signal is the dominant synchronizer for master SCN clock. Downstream from the retina, glutamate and PACAP are released and trigger the activation of signal transduction cascades, including CamKII and nNOS activity, cAMP- and cGMP-dependent protein kinases, and mitogen-activated protein kinase (MAPK). Of non-photic entrainment, important phase shifting capabilities have been found for melatonin, which inhibits light-induced phase shifts through inhibition of adenylate cyclase (AC). Multiple entrainment pathways converge into CREB regulation. In turn, phosphorylated CREB activates clock gene ...

cyclic gmp dependent protein kinasescyclic gmp dependent protein kinases

Research Grants about cyclic gmp dependent protein kinases ... cyclic gmp dependent protein kinases. Summary. Summary: A group ... cyclic nucleotide regulated protein kinases , cyclic gmp dependent protein kinases ... cyclic amp dependent protein kinases*enzyme inhibitors*phosphorylation*carbazoles*cyclic amp*thionucleotides*protein kinase ... Toxoplasma gondii cyclic GMP-dependent kinase: chemotherapeutic targeting of an essential parasite protein kinase. Robert G K ...
more infohttps://www.labome.org/topics/chemicals/and/peptides/intracellular/cyclic/cyclic-gmp-dependent-protein-kinases-13214.html

Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System | Circulation ResearchCyclic GMP-Dependent Protein Kinases and the Cardiovascular System | Circulation Research

Activation of mitogen-activated protein kinase pathways by cyclic GMP and cyclic GMP-dependent protein kinase in contractile ... Cyclic AMP- and cyclic GMP-dependent protein kinases differ in their regulation of cyclic AMP response element-dependent gene ... Cyclic GMP-Dependent Protein Kinases. Genes and Proteins. cGKs are serine/threonine kinases that are present in a variety of ... cAK indicates cAMP-dependent protein kinase; cGK(I/II), cGMP-dependent protein kinase (type I/II); cGMP, cyclic guanosine-3′,5 ...
more infohttp://circres.ahajournals.org/content/93/10/907.full

The Vasodilator-Stimulated Phosphoprotein Is Regulated by Cyclic GMP-Dependent Protein Kinase During Neutrophil Spreading | The...The Vasodilator-Stimulated Phosphoprotein Is Regulated by Cyclic GMP-Dependent Protein Kinase During Neutrophil Spreading | The...

... cyclic AMP-dependent protein kinase; cGK, cyclic GMP-dependent protein kinase; FAK, focal adhesion kinase; GBSS, Geys balanced ... VASP is a prominent substrate for both cGMP-dependent protein kinase (cGK) and cAMP-dependent protein kinase. Evidence ... Cyclic GMP-dependent protein kinase is required for thrombospondin and tenascin mediated focal adhesion disassembly. J. Cell ... Progress in understanding the mechanism and function of cyclic GMP-dependent protein kinase. Adv. Pharmacol. 26: 115. ...
more infohttp://www.jimmunol.org/content/166/9/5550.long

Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissueExpression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue

... Waldkirch, ... cavernosum, corpus, cavernous arteries, cyclic gmp, erectile dysfunction, nitric oxide, protein kinase G. in Journal of Sexual ... cyclic gmp,erectile dysfunction,nitric oxide,protein kinase G}, language = {eng}, number = {3}, pages = {536--543}, publisher ... Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue}, url = {http:// ...
more infohttps://lup.lub.lu.se/search/publication/f3635aba-c569-4a4f-8b20-ff470a58dce8

Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome | Infection and...Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome | Infection and...

Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome. K. Govindasamy, ... Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome ... Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome ... Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome ...
more infohttps://iai.asm.org/content/87/1/e00523-18/figures-only

AMPK and Endothelial Nitric Oxide Synthase Signaling Regulates K-Ras Plasma Membrane Interactions via Cyclic GMP-Dependent...AMPK and Endothelial Nitric Oxide Synthase Signaling Regulates K-Ras Plasma Membrane Interactions via Cyclic GMP-Dependent...

Activation of mitogen-activated protein kinase pathways by cyclic GMP and cyclic GMP-dependent protein kinase in contractile ... AMP-activated protein kinase (AMPK). In dissecting the molecular mechanism, we identified cyclic GMP (cGMP)-dependent protein ... We show here that K-Ras is a substrate for cyclic GMP-dependent protein kinases (PKGs). In intact cells, activated PKG2 ... Nitric Oxide Synthase Signaling Regulates K-Ras Plasma Membrane Interactions via Cyclic GMP-Dependent Protein Kinase 2. Kwang- ...
more infohttps://mcb.asm.org/content/36/24/3086

Phosphorylation of tyrosine hydroxylase by cyclic GMP - Dependent protein kinase<...Phosphorylation of tyrosine hydroxylase by cyclic GMP - Dependent protein kinase<...

... phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase ... phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase ... phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase ... phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase ...
more infohttps://ucdavis.pure.elsevier.com/en/publications/phosphorylation-of-tyrosine-hydroxylase-by-cyclic-gmp-dependent-p

Role of cyclic GMP-dependent protein kinase type II in the brain - UBC Library Open CollectionsRole of cyclic GMP-dependent protein kinase type II in the brain - UBC Library Open Collections

PKG I cyclic GMP-dependent protein kinase type I PKG U cyclic GMP-dependent protein kinase type II pM pico Molar PMSF phenyl ... and cGMP-dependent protein kinases, protein kinase C , calmodulin-dependent protein kinase U and casein kinase LT. Eur J ... Cyclic-GMP-dependent protein kinase inhibits the Ras/Mitogen-activated protein kinase pathway. Mol Cell Biol. 18:6983-94. Surks ... the residues on cyclic GMP-dependent protein kinase that are autophosphorylated in the presence of cyclic A M P and cyclic GMP ...
more infohttps://open.library.ubc.ca/cIRcle/collections/ubctheses/831/items/1.0092443

June 1987 - Volume 5 - Issue 3 : Journal of HypertensionJune 1987 - Volume 5 - Issue 3 : Journal of Hypertension

Activity of Cyclic GMP-Dependent Protein Kinase in Aortae from Spontaneously Hypertensive Rats. Coquil, Jean-François; Brunelle ...
more infohttp://journals.lww.com/jhypertension/toc/1987/06000

Opening mitoKATP increases supero... preview & related info | MendeleyOpening mitoKATP increases supero... preview & related info | Mendeley

Cyclic GMP-Dependent Protein Kinases. *Decanoic Acids. *Diazoxide. *Electron Transport Complex I ... Myxothiazol stimulated mitoK(ATP)-dependent ROS production, whereas rotenone had no effect. This indicates that the superoxide ... dependent stimulation of ROS production is unknown. We examined ROS production in suspensions of isolated rat heart and liver ...
more infohttps://www.mendeley.com/research-papers/opening-mitokatp-increases-superoxide-generation-complex-i-electron-transport-chain/

Control of the Ca2+ Release Induced by myo-Inositol Trisphosphate and the Implication in Signal Transduction | SpringerLinkControl of the Ca2+ Release Induced by myo-Inositol Trisphosphate and the Implication in Signal Transduction | SpringerLink

5-trisphosphate receptor by cyclic GMP-dependent protein kinase, J. Biol. Chem. 269:8701-8707.PubMedGoogle Scholar ... phosphorylation by protein kinase C and calcium calmodulin-dependent protein kinases in reconstituted lipid vesicles, Proc. ... Effect of cAMP-dependent protein kinase, Am. J. Physiol. 258:C1086-C1091.PubMedGoogle Scholar ... Cyclic AMP-dependent kinase augments inositol trisphosphate-mediated Ca2+ mobilization without increasing the cellular levels ...
more infohttps://link.springer.com/chapter/10.1007/978-1-4613-0343-5_3

Cyclic GMP, Synthesis, Metabolism, and Function: Volume 26 by J. Thomas August | 9780120329267 | BooktopiaCyclic GMP, Synthesis, Metabolism, and Function: Volume 26 by J. Thomas August | 9780120329267 | Booktopia

Buy a discounted Hardcover of Cyclic GMP online from Australias leading online bookstore. ... Booktopia has Cyclic GMP, Synthesis, Metabolism, and Function: Volume 26 by J. Thomas August. ... Cyclic GMP-dependent protein kinase. * Hormones and ligands that regulate GMP formation and/or metabolism. * Effects of cyclic ... cyclic GMP-dependent protein kinases, and various hormones and ligands that regulate cyclic GMP formation and/or metabolism. ...
more infohttps://www.booktopia.com.au/cyclic-gmp-j-thomas-august/prod9780120329267.html

Frontiers in Bioscience: A virtual library of medicineFrontiers in Bioscience: A virtual library of medicine

Cyclic GMP-dependent protein kinases in protozoa. David A. Baker, Wensheng Deng. [Frontiers In Bioscience, Landmark, 10, 1229 ... Role of protein kinases in neurodegenerative disease: cyclin-dependent kinases in Alzheimers disease. Edward A. Monaco III and ... Molecular properties and biological functions of cGMP-dependent protein kinase II. Arie B. Vaandrager, Boris M. Hogema, Hugo R ... Tracking functions of cGMP-dependent protein kinases (cGK). Suzanne M. Lohmann, Ulrich Walter. [Frontiers In Bioscience, ...
more infohttps://www.bioscience.org/landmark/10l/2005

Biological functions of hydrogen sulfide - WikipediaBiological functions of hydrogen sulfide - Wikipedia

"Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype". Journal of Vascular Research. 34 (4): 245 ... Lincoln, T. M.; Cornwell, Taylor (March 1990). "cGMP-dependent protein kinase mediates the reduction of Ca2+ by cAMP in ... increased cGMP triggers an increase in protein kinase G (PKG) activity. PKG reduces intracellular Ca2+ in vascular smooth ... "Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent ...
more infohttps://en.wikipedia.org/wiki/Biological_functions_of_hydrogen_sulfide

Gaseous signaling molecules - WikipediaGaseous signaling molecules - Wikipedia

"Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype". Journal of Vascular Research. 34 (4): 245 ... which is a heterodimeric enzyme with subsequent formation of cyclic-GMP. Cyclic-GMP activates protein kinase G, which causes ... Lincoln, T. M.; Cornwell, Taylor (March 1990). "cGMP-dependent protein kinase mediates the reduction of Ca2+ by cAMP in ... Ethylene is perceived by a family of five transmembrane protein dimers such as the ETR1 protein in Arabidopsis. The gene ...
more infohttps://en.wikipedia.org/wiki/Gaseous_signaling_molecules

KEGG ENZYME: 2.7.11.12KEGG ENZYME: 2.7.11.12

cGMP-dependent protein kinase;. 3:5-cyclic GMP-dependent protein kinase;. cGMP-dependent protein kinase Ibeta;. guanosine 3: ... Progressive cyclic nucleotide-induced conformational changes in the cGMP-dependent protein kinase studied by small angle X-ray ... 5-cyclic monophosphate-dependent protein kinase;. PKG;. PKG 1alpha;. PKG 1beta;. PKG II;. STK23. ... Dimerization of cGMP-dependent protein kinase Ibeta is mediated by an extensive amino-terminal leucine zipper motif, and ...
more infohttps://www.genome.jp/dbget-bin/www_bget?ec:2.7.11.12

Myosin phosphatase: structure, regulation and function.Myosin phosphatase: structure, regulation and function.

The level of myosin II phosphorylation is determined by activities of myosin light chain kinase and myosin phosphatase (MP). MP ... EC 2.7.11.12/Cyclic GMP-Dependent Protein Kinases; EC 3.1.3.16/Phosphoprotein Phosphatases; EC 3.1.3.16/Protein Phosphatase 1; ... Cyclic GMP-Dependent Protein Kinases / genetics, metabolism. Gene Expression Regulation, Developmental. Humans. Membrane ... 0/Membrane Proteins; 0/Muscle Proteins; 0/PPP1R14A protein, human; 0/PPP1R16B protein, human; 0/Phosphoproteins; 0/Protein ...
more infohttp://www.biomedsearch.com/nih/Myosin-phosphatase-structure-regulation-function/15124925.html

Modulation of Cl-/OH- exchange activity in Caco-2 cells by nitric oxide.Modulation of Cl-/OH- exchange activity in Caco-2 cells by nitric oxide.

Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors. Cyclic GMP / physiology. Cyclic GMP-Dependent Protein Kinases ... EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.12/Cyclic GMP-Dependent Protein Kinases ... 10688876 - Erectile dysfunction in cyclic gmp-dependent kinase i-deficient mice.. 22972416 - Stable liquid glucagon ... cyclic phosphorothioate; 60-92-4/Cyclic AMP; 7665-99-8/Cyclic GMP; 79032-48-7/S-Nitroso-N-Acetylpenicillamine; ...
more infohttp://www.biomedsearch.com/nih/Modulation-Cl-exchange-activity-in/12181176.html

RGS4 Gene - GeneCards | RGS4 Protein | RGS4 AntibodyRGS4 Gene - GeneCards | RGS4 Protein | RGS4 Antibody

Protein Coding), Regulator Of G Protein Signaling 4, including: function, proteins, disorders, pathways, orthologs, and ... Phosphorylated by cyclic GMP-dependent protein kinase. *P49798-RGS4_HUMAN. * Modification sites at PhosphoSitePlus *P49798 ... G-protein coupled receptor signaling pathway. IEA. --. GO:0008277. regulation of G-protein coupled receptor protein signaling ... Protein Symbol:. P49798-RGS4_HUMAN. Recommended name:. Regulator of G-protein signaling 4. Protein Accession:. P49798. ...
more infohttps://www.genecards.org/cgi-bin/carddisp.pl?gene=RGS4

TNO Repository search for: subject:AutoradiographyTNO Repository search for: subject:'Autoradiography'

GMP, 54364-02-2; Calcium Channels; Cell Adhesion Molecules; Cyclic GMP, 7665-99-8; Cyclic GMP-Dependent Protein Kinases, EC 2.7 ... Cyclic GMP · Cyclic GMP-Dependent Protein Kinases · Cytoplasm · Endothelium, Vascular · Enzyme Activation · Hemostasis · Human ... cyclic GMP · calcium ion · cyclic GMP · cyclic GMP derivative · fura 2 · horseradish peroxidase · phosphoprotein · protein ... protein kinase C · protein kinase C inhibitor · recombinant interleukin 1beta · recombinant tumor necrosis factor alpha · tumor ...
more infohttps://repository.tudelft.nl/search/tno/?q=subject:%22Autoradiography%22

Endothelial Nitric Oxide Synthase Inhibits G12/13 and Rho-Kinase Activated by the Angiotensin II Type-1 Receptor |...Endothelial Nitric Oxide Synthase Inhibits G12/13 and Rho-Kinase Activated by the Angiotensin II Type-1 Receptor |...

Hofmann F. The biology of cyclic GMP-dependent protein kinases. J Biol Chem. 2005; 280: 1-4. ... Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular ... cGMP-dependent protein kinase inhibits serum-response element-dependent transcription by inhibiting rho activation and ... 7-10 We have recently reported that eNOS gene transfer activates the NO/cyclic GMP (cGMP)/protein kinase G (PKG) cascade and ...
more infohttp://atvb.ahajournals.org/content/29/2/217.full

The Role of cGMP-Dependent Protein Kinase in Controlling Cardiomyocyte cGMP | Circulation ResearchThe Role of cGMP-Dependent Protein Kinase in Controlling Cardiomyocyte cGMP | Circulation Research

Cyclic GMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev. 2010;62:525- ... Regulation and role of myocyte cyclic GMP-dependent protein kinase-1. Proc Natl Acad Sci U S A. 2010;107:E98. ... The biology of cyclic GMP-dependent protein kinases. J Biol Chem. 2005;280:1-4. ... cGMP-dependent protein kinase I. RGS. regulator of G protein-coupled signaling. TnI. troponin I. ...
more infohttp://circres.ahajournals.org/content/107/10/1164

Plus itPlus it

1998) Cyclic-GMP-dependent protein kinase inhibits the Ras/mitogen-activated protein kinase pathway. Mol Cell Biol 18:6983-6994 ... Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification ... 1994) High-affinity binding and localization of the cyclic GMP-dependent protein kinase with the intermediate filament protein ... 1997) Cyclic GMP-dependent protein kinase and cellular signaling in the nervous system. J Neurochem 68:443-456. ...
more infohttp://www.jneurosci.org/content/21/11/3871

cGMP-dependent changes in phototaxis: a possible role for the foraging gene in honey bee division of labor | Journal of...cGMP-dependent changes in phototaxis: a possible role for the foraging gene in honey bee division of labor | Journal of...

Ruth, P. (1999). Cyclic GMP-dependent protein kinases: understanding in vivo functions by gene targeting. Pharm. Ther. 82,355 - ... Wang, X. and Robinson, P. J. (1997). Cyclic GMP-dependent protein kinase and cellular signaling in the nervous system. J. ... The cyclic GMP-dependent protein kinase EGL-4 regulates olfactory adaptation in C. elegans. Neuron 36,1079 -1089. ... Engel, J. E., Xie, X. J., Sokolowski, M. B. and Wu, C. F. (2000). A cGMP-dependent protein kinase gene, foraging, modifies ...
more infohttp://jeb.biologists.org/content/206/14/2507

Enhanced Recovery of Injury-Caused Downregulation of Paxillin Protein by eNOS Gene Expression in Rat Carotid Artery |...Enhanced Recovery of Injury-Caused Downregulation of Paxillin Protein by eNOS Gene Expression in Rat Carotid Artery |...

... whether NO upregulates paxillin through a cyclic GMP-dependent protein kinase pathway or through inhibition of paxillin protein ... Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype. J Vasc Res. 1997;34:245-259. ... In fact, NO has been found to regulate vascular SMC differentiation through the cyclic GMP-dependent protein kinase pathway.27 ... Although evidence suggests that NO may stimulate SMC differentiation through the cyclic GMP-dependent protein kinase pathway, ...
more infohttp://atvb.ahajournals.org/content/19/1/147.long
  • Conclusion- The eNOS/NO cascade specifically targets the Rho/Rho-kinase system via inhibition of G 12/13 to prevent vascular migration induced by AngII, representing a novel signal cross-talk in cardiovascular protection by NO. (ahajournals.org)
  • Moreover, inhibition of G6PD increased protein kinase G1α activity, which, at least partially, mitigated superoxide production and Elk-1 and TNF-α expression. (physiology.org)
  • Although it is generally accepted that many NO effects are mediated via elevation of intracellular cGMP, one should keep in mind that NO can exert effects independent of cGMP production, for instance via modification of cellular proteins by S-nitrosylation of cysteine residues. (ahajournals.org)
  • Several chapters also deal with some of the effects of cyclic GMP on other second messengers such as calcium ion transport and smooth muscle relaxation. (booktopia.com.au)
  • Gene Ontology (GO) annotations related to this gene include GTPase activator activity and G-protein alpha-subunit binding . (genecards.org)
  • Each G protein contains an alpha-, beta- and gamma-subunit and is bound to GDP in the 'off' state. (genecards.org)
  • Full length wt PKG II and wt regulatory PKG JJ proteins, when overexpressed in hippocampal neurons targeted to the synapse, however, a G2A PKG II mutant, which does not undergo myristoylation had a much more diffuse distribution in the entire cell and did not target to the synapse. (ubc.ca)
  • Taken together, paxillin may function as a structural protein to maintain the integrity of the SMC contractile apparatus and as a docking protein to potentially mediate signal transduction for SMC contraction, migration, proliferation, and possibly differentiation. (ahajournals.org)
  • A) Western blotting confirmed expression of fusion proteins in in vitro -transcribed/translated wheat germ extracts. (asm.org)
  • The expression of paxillin and its associated proteins was determined in injured arteries by Western blot analysis. (ahajournals.org)
  • In addition to the induction of NOS1, estrogen increases the expression of antiapoptotic protein such as bcl-2. (elsevier.com)
  • They play essential roles as transcriptional activators of the HEAT-SHOCK RESPONSE by inducing expression of large classes of MOLECULAR CHAPERONES and heat-shock proteins. (bioportfolio.com)
  • We then determined whether cGMP is present in presynaptic retinal terminals by the use of double-labeling for cGMP and either the presynaptic protein synaptophysin or a fluorescent anterograde tracer injected into the eye to label retinal terminals unambiguously in the dLGN. (jneurosci.org)
  • In contrast, blockers of the ADP-ribosyltransferase primarily reduced LTP, suggesting that NO, at least partly, acts via ADP-ribosylation of presynaptic proteins. (jneurosci.org)
  • 1 2 3 4 5 At the focal adhesion sites, paxillin is associated with the actin filament-binding protein vinculin. (ahajournals.org)
  • Using wild type (wt) and non-myristoylated mutant PKG II proteins it was demonstrated that N-myristoylation (N-myr) is important for targeting of PKG II to membranes and distal ends of filopodia like structures in COS-1 and HEK-293 cells. (ubc.ca)
  • To investigate which proteins were involved in this induction, endothelial cells were incubated with and without TNFα in the presence of 14C-galactose or 14C-glucose. (tudelft.nl)
  • In this regard, AngII stimulates hypertrophy, proliferation, and migration of vascular smooth muscle cells (VSMCs) through a G protein-coupled receptor (GPCR), the AngII type-1 receptor (AT 1 ). (ahajournals.org)
  • Thermotolerance is a phenomenon in which cells become resistant to stress by prior exposure to heat shock, and its development is associated with the induction of heat shock proteins (Hsps), including. (bioportfolio.com)
  • RATIONALE: Vaccines made from a person's tumor cells, such as gp96 heat shock protein-peptide complex, may help the body build an effective immune response to kill tumor cells. (bioportfolio.com)
  • Besides the bioavailability of nitric oxide (NO), downstream guanine monophosphate (cGMP) effector proteins are also considered to play a significant role in penile vascular disease. (lu.se)
  • RGS4 (Regulator Of G Protein Signaling 4) is a Protein Coding gene. (genecards.org)
  • Division of labor in honey bee colonies is influenced by the foraging gene ( Amfor ), which encodes a cGMP-dependent protein kinase (PKG). (biologists.org)
  • 20-hydroxyeicosatetraeonic acid (20-HETE), the ω-hydroxylation metabolite of arachidonic acid (AA), is produced by cytochrome P -450 monooxygenases of the (CYP4A and CYP4F gene) families in an NADPH-dependent manner ( 49 ). (physiology.org)
  • We thus proposed that the estrogen-mediated gene induction of Trx plays a pivotal role in the promotion of neuroprotection because Trx is a multifunctional antioxidative and antiapoptotic protein. (elsevier.com)
  • VASP is believed to play an important role in controlling the cytoskeletal organization because it binds filamentous actin (F-actin) and profilin, a protein that forms complexes with G-actin and regulates actin dynamics ( 2 , 11 , 12 ). (jimmunol.org)
  • The critical role of RhoA/Rho-kinase signaling in various systems is discussed, in particular those vascular smooth muscle disorders involving hypercontractility. (biomedsearch.com)
  • As a member of the LIM domain-containing proteins, paxillin may play an important role in the differentiation of vascular SMCs. (ahajournals.org)
  • 12 13 SmCRP, an LIM protein cloned from rat aorta, has been found to play a role in the differentiation of vascular SMCs. (ahajournals.org)
  • Interestingly, a homolog of EGL-4 in Drosophila was shown to play a role in natural variation of foraging behavior, indicating a conserved role of cGMP-dependent protein kinases as a modulator of interspecies behaviors. (pnas.org)
  • HSP40 heat-shock proteins play a role in regulating the ADENOSINE TRIPHOSPHATASES activity of HSP70 heat-shock proteins. (bioportfolio.com)
  • The vasodilator-stimulated phosphoprotein (VASP) 4 is a 46-kDa membrane-associated protein that is a member of the Enabled (Ena) family of proteins. (jimmunol.org)
  • Induction of heat shock protein 72 in the failing heart is attenuated after an exposure to heat shoc. (biomedsearch.com)
  • A split-luciferase protein complementation assay was used to test interaction between the PfPKG kinase domain (PfPKG E 706 A and PfPKG R 781 A) and a fragment of RPT1 (amino acids 114 to 420) or HSP90 (amino acids 228 to 518). (asm.org)
  • These fusion proteins were used in subsequent complementation assays. (asm.org)
  • The negative inotropism was insensitive to losartan and CGP42112 (AT 1 and AT 2 ANG II receptor antagonists, respectively), and was abrogated by the AT 1 receptor antagonist CV11974, the G protein blocker pertussis toxin (PTx) and the muscarinic antagonist atropine. (biologists.org)
  • Intestinal Fatty Acid Binding Protein is Associated with Mortality in Patients with Acute Heart Failure or Cardiogenic Shock. (bioportfolio.com)
  • Acute heart failure and cardiogenic shock are associated with an impaired intestinal perfusion, which may lead to a release of cytoplasmatic proteins by hypoxic epithelial injury. (bioportfolio.com)