Cystic Fibrosis Transmembrane Conductance Regulator: A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)Cystic Fibrosis: An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.Chloride Channels: Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.Mice, Inbred CFTR: A strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Ion Channel Gating: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.Nasal Mucosa: The mucous lining of the NASAL CAVITY, including lining of the nostril (vestibule) and the OLFACTORY MUCOSA. Nasal mucosa consists of ciliated cells, GOBLET CELLS, brush cells, small granule cells, basal cells (STEM CELLS) and glands containing both mucous and serous cells.Gold Compounds: Inorganic compounds that contain gold as an integral part of the molecule.Iodides: Inorganic binary compounds of iodine or the I- ion.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Respiratory Mucosa: The mucous membrane lining the RESPIRATORY TRACT, including the NASAL CAVITY; the LARYNX; the TRACHEA; and the BRONCHI tree. The respiratory mucosa consists of various types of epithelial cells ranging from ciliated columnar to simple squamous, mucous GOBLET CELLS, and glands containing both mucous and serous cells.ortho-Aminobenzoates: Benzoic acids, salts, or esters that contain an amino group attached to carbon number 2 or 6 of the benzene ring structure.Aminophenols: Phenols substituted in any position by an amino group.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.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Bicarbonates: Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the pH of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid: An inhibitor of anion conductance including band 3-mediated anion transport.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.1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASESProtein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching.Sweat: The fluid excreted by the SWEAT GLANDS. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Eosine I Bluish: A red fluorescein dye used as a histologic stain. It may be cytotoxic, mutagenic, and inhibit certain mitochondrial functions.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Nitrobenzoates: Benzoic acid or benzoic acid esters substituted with one or more nitro groups.Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Adenylyl Imidodiphosphate: 5'-Adenylic acid, monoanhydride with imidodiphosphoric acid. An analog of ATP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It is a potent competitive inhibitor of soluble and membrane-bound mitochondrial ATPase and also inhibits ATP-dependent reactions of oxidative phosphorylation.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.Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.Genistein: An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.Mesylates: Organic salts or esters of methanesulfonic acid.Epithelial Sodium Channels: Sodium channels found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON; the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. They are AMILORIDE-sensitive and play a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.Biotinylation: Incorporation of biotinyl groups into molecules.Amiloride: A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)Epithelium: One or more layers of EPITHELIAL CELLS, supported by the basal lamina, which covers the inner or outer surfaces of the body.Thiazolidines: Reduced (protonated) form of THIAZOLES. They can be oxidized to THIAZOLIDINEDIONES.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Sodium-Hydrogen Antiporter: A plasma membrane exchange glycoprotein transporter that functions in intracellular pH regulation, cell volume regulation, and cellular response to many different hormones and mitogens.Oocytes: Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Vas Deferens: The excretory duct of the testes that carries SPERMATOZOA. It rises from the SCROTUM and joins the SEMINAL VESICLES to form the ejaculatory duct.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)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.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Chloride-Bicarbonate Antiporters: Electroneutral chloride bicarbonate exchangers that allow the exchange of BICARBONATE IONS exchange for CHLORIDE IONS across the cellular membrane. The action of specific antiporters in this class serve important functions such as allowing the efficient exchange of bicarbonate across red blood cell membranes as they passage through capillaries and the reabsorption of bicarbonate ions by the kidney.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Xenopus laevis: The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Kinetics: The rate dynamics in chemical or physical systems.Pancreatic Ducts: Ducts that collect PANCREATIC JUICE from the PANCREAS and supply it to the DUODENUM.Sweat Glands: Sweat-producing structures that are embedded in the DERMIS. Each gland consists of a single tube, a coiled body, and a superficial duct.HSC70 Heat-Shock Proteins: A constitutively expressed subfamily of the HSP70 heat-shock proteins. They preferentially bind and release hydrophobic peptides by an ATP-dependent process and are involved in post-translational PROTEIN TRANSLOCATION.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Pseudomonas Infections: Infections with bacteria of the genus PSEUDOMONAS.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.TetramisoleCyanates: Organic salts of cyanic acid containing the -OCN radical.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Pseudomonas aeruginosa: A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.Nucleotides: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)Antiporters: Membrane transporters that co-transport two or more dissimilar molecules in the opposite direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Mucociliary Clearance: A non-specific host defense mechanism that removes MUCUS and other material from the LUNGS by ciliary and secretory activity of the tracheobronchial submucosal glands. It is measured in vivo as mucus transfer, ciliary beat frequency, and clearance of radioactive tracers.Exocrine Glands: Glands of external secretion that release its secretions to the body's cavities, organs, or surface, through a duct.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Epithelial Sodium Channel Blockers: A subclass of sodium channel blockers that are specific for EPITHELIAL SODIUM CHANNELS.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Sodium-Potassium-Chloride Symporters: A subclass of symporters that specifically transport SODIUM CHLORIDE and/or POTASSIUM CHLORIDE across cellular membranes in a tightly coupled process.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.PhenylbutyratesBenzoates: Derivatives of BENZOIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxybenzene structure.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.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Sodium Channels: Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.Cricetulus: A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about.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.Cell Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains.Diphosphates: Inorganic salts of phosphoric acid that contain two phosphate groups.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Fundulidae: Family of small, surface-dwelling fish that inhabit fresh and brackish waters, and coastal marine areas.RNA, Complementary: Synthetic transcripts of a specific DNA molecule or fragment, made by an in vitro transcription system. This cRNA can be labeled with radioactive uracil and then used as a probe. (King & Stansfield, A Dictionary of Genetics, 4th ed)Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells.Solute Carrier Family 12, Member 2: Na-K-Cl transporter ubiquitously expressed. It plays a key role in salt secretion in epithelial cells and cell volume regulation in nonepithelial cells.Quinolinium Compounds3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.Thiocyanates: Organic derivatives of thiocyanic acid which contain the general formula R-SCN.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Homozygote: An individual in which both alleles at a given locus are identical.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Calnexin: A lectin found in ENDOPLASMIC RETICULUM membranes that binds to specific N-linked OLIGOSACCHARIDES found on newly synthesized proteins. It may play role in PROTEIN FOLDING or retention and degradation of misfolded proteins in the endoplasmic reticulum.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Colon: The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Respiratory System Agents: Drugs used for their effects on the respiratory system.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Mutant Proteins: Proteins produced from GENES that have acquired MUTATIONS.QuinolizinesTrypsinogen: The inactive proenzyme of trypsin secreted by the pancreas, activated in the duodenum via cleavage by enteropeptidase. (Stedman, 25th ed)Urogenital Abnormalities: Congenital structural abnormalities of the UROGENITAL SYSTEM in either the male or the female.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.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).Natriuretic Peptides: Peptides that regulate the WATER-ELECTROLYTE BALANCE in the body, also known as natriuretic peptide hormones. Several have been sequenced (ATRIAL NATRIURETIC FACTOR; BRAIN NATRIURETIC PEPTIDE; C-TYPE NATRIURETIC PEPTIDE).Azides: Organic or inorganic compounds that contain the -N3 group.Nasal Polyps: Focal accumulations of EDEMA fluid in the NASAL MUCOSA accompanied by HYPERPLASIA of the associated submucosal connective tissue. Polyps may be NEOPLASMS, foci of INFLAMMATION, degenerative lesions, or malformations.Gills: Paired respiratory organs of fishes and some amphibians that are analogous to lungs. They are richly supplied with blood vessels by which oxygen and carbon dioxide are exchanged directly with the environment.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Bumetanide: A sulfamyl diuretic.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.HSP40 Heat-Shock Proteins: A family of heat-shock proteins that contain a 70 amino-acid consensus sequence known as the J domain. The J domain of HSP40 heat shock proteins interacts with HSP70 HEAT-SHOCK PROTEINS. HSP40 heat-shock proteins play a role in regulating the ADENOSINE TRIPHOSPHATASES activity of HSP70 heat-shock proteins.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Mice, Inbred C57BLSodium-Bicarbonate Symporters: Proteins that cotransport sodium ions and bicarbonate ions across cellular membranes.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Lissamine Green Dyes: Green dyes containing ammonium and aryl sulfonate moieties that facilitate the visualization of tissues, if given intravenously. They have mostly been used in the study of kidney physiology.Cation Exchange Resins: High molecular weight insoluble polymers which contain functional anionic groups that are capable of undergoing exchange reactions with cations.Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.Body Fluids: Liquid components of living organisms.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.P-Glycoprotein: A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Antidiarrheals: Miscellaneous agents found useful in the symptomatic treatment of diarrhea. They have no effect on the agent(s) that cause diarrhea, but merely alleviate the condition.Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Niflumic Acid: An analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis.Benzbromarone: Uricosuric that acts by increasing uric acid clearance. It is used in the treatment of gout.Anion Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of negatively charged molecules (anions) across a biological membrane.Sodium Channel Blockers: A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.Diffusion Chambers, Culture: Devices used in a technique by which cells or tissues are grown in vitro or, by implantation, in vivo within chambers permeable to diffusion of solutes across the chamber walls. The chambers are used for studies of drug effects, osmotic responses, cytogenic and immunologic phenomena, metabolism, etc., and include tissue cages.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.PhosphoproteinsThionucleotides: Nucleotides in which the base moiety is substituted with one or more sulfur atoms.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.Caco-2 Cells: Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells, such as ENTEROCYTES. These cells are valuable in vitro tools for studies related to intestinal cell function and differentiation.Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.CresolsImmunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Pancreas: A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Chlorophenols: Phenols substituted with one or more chlorine atoms in any position.Water-Electrolyte Balance: The balance of fluid in the BODY FLUID COMPARTMENTS; total BODY WATER; BLOOD VOLUME; EXTRACELLULAR SPACE; INTRACELLULAR SPACE, maintained by processes in the body that regulate the intake and excretion of WATER and ELECTROLYTES, particularly SODIUM and POTASSIUM.Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.Spodoptera: A genus of owlet moths of the family Noctuidae. These insects are used in molecular biology studies during all stages of their life cycle.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Proteolysis: Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as CATIONS; those with a negative charge are ANIONS.Adenylate Kinase: An enzyme that catalyzes the phosphorylation of AMP to ADP in the presence of ATP or inorganic triphosphate. EC 2.7.4.3.

Cystic fibrosis transmembrane conductance regulator-mediated corneal epithelial cell ingestion of Pseudomonas aeruginosa is a key component in the pathogenesis of experimental murine keratitis. (1/2621)

Previous findings indicate that the cystic fibrosis transmembrane conductance regulator (CFTR) is a ligand for Pseudomonas aeruginosa ingestion into respiratory epithelial cells. In experimental murine keratitis, P. aeruginosa enters corneal epithelial cells. We determined the importance of CFTR-mediated uptake of P. aeruginosa by corneal cells in experimental eye infections. Entry of noncytotoxic (exoU) P. aeruginosa into human and rabbit corneal cell cultures was inhibited with monoclonal antibodies and peptides specific to CFTR amino acids 108 to 117. Immunofluorescence microscopy and flow cytometry demonstrated CFTR in the intact murine corneal epithelium, and electron microscopy showed that CFTR binds to P. aeruginosa following corneal cell ingestion. In experimental murine eye infections, multiple additions of 5 nM CFTR peptide 103-117 to inocula of either cytotoxic (exoU+) or noncytotoxic P. aeruginosa resulted in large reductions in bacteria in the eye and markedly lessened eye pathology. Compared with wild-type C57BL/6 mice, heterozygous DeltaF508 Cftr mice infected with P. aeruginosa had an approximately 10-fold reduction in bacterial levels in the eye and consequent reductions in eye pathology. Homozygous DeltaF508 Cftr mice were nearly completely resistant to P. aeruginosa corneal infection. CFTR-mediated internalization of P. aeruginosa by buried corneal epithelial cells is critical to the pathogenesis of experimental eye infection, while in the lung, P. aeruginosa uptake by surface epithelial cells enhances P. aeruginosa clearance from this tissue.  (+info)

Cystic fibrosis-associated mutations at arginine 347 alter the pore architecture of CFTR. Evidence for disruption of a salt bridge. (2/2621)

Arginine 347 in the sixth transmembrane domain of cystic fibrosis transmembrane conductance regulator (CFTR) is a site of four cystic fibrosis-associated mutations. To better understand the function of Arg-347 and to learn how mutations at this site disrupt channel activity, we mutated Arg-347 to Asp, Cys, Glu, His, Leu, or Lys and examined single-channel function. Every Arg-347 mutation examined, except R347K, had a destabilizing effect on the pore, causing the channel to flutter between two conductance states. Chloride flow through the larger conductance state was similar to that of wild-type CFTR, suggesting that the residue at position 347 does not interact directly with permeating anions. We hypothesized that Arg-347 stabilizes the channel through an electrostatic interaction with an anionic residue in another transmembrane domain. To test this, we mutated anionic residues (Asp-924, Asp-993, and Glu-1104) to Arg in the context of either R347E or R347D mutations. Interestingly, the D924R mutation complemented R347D, yielding a channel that behaved like wild-type CFTR. These data suggest that Arg-347 plays an important structural role in CFTR, at least in part by forming a salt bridge with Asp-924; cystic fibrosis-associated mutations disrupt this interaction.  (+info)

CFTR channel insertion to the apical surface in rat duodenal villus epithelial cells is upregulated by VIP in vivo. (3/2621)

cAMP activated insertion of the cystic fibrosis transmembrane conductance regulator (CFTR) channels from endosomes to the apical plasma membrane has been hypothesized to regulate surface expression and CFTR function although the physiologic relevance of this remains unclear. We previously identified a subpopulation of small intestinal villus epithelial cells or CFTR high expressor (CHE) cells possessing very high levels of apical membrane CFTR in association with a prominent subapical vesicular pool of CFTR. We have examined the subcellular redistribution of CFTR in duodenal CHE cells in vivo in response to the cAMP activated secretagogue vasoactive intestinal peptide (VIP). Using anti-CFTR antibodies against the C terminus of rodent CFTR and indirect immunofluorescence, we show by quantitative confocal microscopy that CFTR rapidly redistributes from the cytoplasm to the apical surface upon cAMP stimulation by VIP and returns to the cytoplasm upon removal of VIP stimulation of intracellular cAMP levels. Using ultrastructural and confocal immunofluorescence examination in the presence or absence of cycloheximide, we also show that redistribution was not dependent on new protein synthesis, changes in endocytosis, or rearrangement of the apical cytoskeleton. These observations suggest that physiologic cAMP activated apical membrane insertion and recycling of CFTR channels in normal CFTR expressing epithelia contributes to the in vivo regulation of CFTR mediated anion transport.  (+info)

beta3-adrenoceptor control the cystic fibrosis transmembrane conductance regulator through a cAMP/protein kinase A-independent pathway. (4/2621)

In human cardiac myocytes, we have previously identified a functional beta3-adrenoceptor in which stimulation reduces action potential duration. Surprisingly, in cardiac biopsies obtained from cystic fibrosis patients, beta3-adrenoceptor agonists produced no effects on action potential duration. This result suggests the involvement of cystic fibrosis transmembrane conductance regulator (CFTR) chloride current in the electrophysiological effects of beta3-adrenoceptor stimulation in non-cystic fibrosis tissues. We therefore investigated the control of CFTR activity by human beta3-adrenoceptors in a recombinant system: A549 human cells were intranuclearly injected with plasmids encoding CFTR and beta3-adrenoceptors. CFTR activity was functionally assayed using the 6-methoxy-N-(3-sulfopropyl)quinolinium fluorescent probe and the patch-clamp technique. Injection of CFTR-cDNA alone led to the expression of a functional CFTR protein activated by cAMP or cGMP. Co-expression of CFTR (but not of mutated DeltaF508-CFTR) with high levels of beta3-adrenoceptor produced an increased halide permeability under base-line conditions that was not further sensitive to cAMP or beta3-adrenoceptor stimulation. Patch-clamp experiments confirmed that CFTR channels were permanently activated in cells co-expressing CFTR and a high level of beta3-adrenoceptor. Permanent CFTR activation was not associated with elevated intracellular cAMP or cGMP levels. When the expression level of beta3-adrenoceptor was lowered, CFTR was not activated under base-line conditions but became sensitive to beta3-adrenoceptor stimulation (isoproterenol plus nadolol, SR 58611, or CGP 12177). This later effect was not prevented by protein kinase A inhibitors. Our results provide molecular evidence that CFTR but not mutated DeltaF508-CFTR is regulated by beta3-adrenoceptors expression through a protein kinase A-independent pathway.  (+info)

Molecular analysis of the cystic fibrosis gene reveals a high frequency of the intron 8 splice variant 5T in Egyptian males with congenital bilateral absence of the vas deferens. (5/2621)

It has previously been shown that defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are largely responsible for the condition of congenital bilateral absence of the vas deferens (CBAVD), without associated renal abnormalities, in Caucasian populations. To assess the involvement of the CFTR in CBAVD in a population with presumed low cystic fibrosis (CF) frequency, we have analysed 20 CBAVD males from Egypt for the presence of 12 common Caucasian CFTR mutations and the intron 8 5T splice variant, IVS-5T, known to be a major cause of CBAVD in Caucasian patients. In 16 of the males without associated renal abnormalities only one deltaF508 carrier was identified, but an exceptionally high frequency of the IVS-5T variant was found (14 of 32 alleles or 43.7%), confirming that this variant is involved in many cases of CBAVD, even in populations where CF is rare. CFTR mutations or the IVS-5T variant were found neither in the remaining four patients with associated renal abnormalities nor in the spouses of the 20 CBAVD patients. However, one patient was homozygous for a leucine to proline substitution at amino acid position 541 (L541P) of the CFTR. It is as yet not clear whether this change is involved in CBAVD in this male.  (+info)

Functional dissection of the R domain of cystic fibrosis transmembrane conductance regulator. (6/2621)

Exogenously expressed unphosphorylated sub-domains of the R domain block CFTR Cl- channels in the planar lipid bilayer, though the block differs from block with full length R domain. Full length R domain peptide (aa 588-855) blocks CFTR Cl- channels quickly, completely and permanently. Two sub-domains, RD1RD2 (aa 588-805) and RD2TM (aa 672-855), also inhibit CFTR Cl- channels, but the block takes longer to effect and is not complete. Shorter sequences, RD1 (aa 588-746) and RD2 (aa 672-805), fail to effect any block. These data suggest that either the amino-terminal or carboxy-terminal portions of the R domain protein or its stabilized secondary structure are critical to functional regulation.  (+info)

Chemokine expression in CF epithelia: implications for the role of CFTR in RANTES expression. (7/2621)

To delineate the mechanisms that facilitate leukocyte migration into the cystic fibrosis (CF) lung, expression of chemokines, including interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and RANTES, was compared between CF and non-CF airway epithelia. The findings presented herein demonstrate that, under either basal conditions or tumor necrosis factor-alpha (TNF-alpha)- and/or interferon-gamma (IFN-gamma)-stimulated conditions, a consistent pattern of differences in the secretion of IL-8 and MCP-1 between CF and non-CF epithelial cells was not observed. In contrast, CF epithelial cells expressed no detectable RANTES protein or mRNA under basal conditions or when stimulated with TNF-alpha and/or IFN-gamma (P +info)

A single conductance pore for chloride ions formed by two cystic fibrosis transmembrane conductance regulator molecules. (8/2621)

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent protein kinase (PKA)- and ATP-regulated chloride channel, whose gating process involves intra- or intermolecular interactions among the cytosolic domains of the CFTR protein. Tandem linkage of two CFTR molecules produces a functional chloride channel with properties that are similar to those of the native CFTR channel, including trafficking to the plasma membrane, ATP- and PKA-dependent gating, and a unitary conductance of 8 picosiemens (pS). A heterodimer, consisting of a wild type and a mutant CFTR, also forms an 8-pS chloride channel with mixed gating properties of the wild type and mutant CFTR channels. The data suggest that two CFTR molecules interact together to form a single conductance pore for chloride ions.  (+info)

*Cystic fibrosis transmembrane conductance regulator

"Cystic fibrosis transmembrane conductance regulator and the etiology and pathogenesis of cystic fibrosis". FASEB J. 6 (10): ... The Cystic Fibrosis Transmembrane Conductance Regulator Protein The Human Gene Mutation Database - CFTR Records Cystic Fibrosis ... "Relationships between cystic fibrosis transmembrane conductance regulator, extracellular nucleotides and cystic fibrosis". ... Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and chloride channel in vertebrates that is ...

*PRKG1

"Phosphorylation of the cystic fibrosis transmembrane conductance regulator". The Journal of Biological Chemistry. 267 (18): ... "Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure". Nature Medicine. 9 (12): ... "cGMP-dependent protein kinase I beta physically and functionally interacts with the transcriptional regulator TFII-I". The ...

*Proteopathy

For example, cystic fibrosis is caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein, and ... "The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability". Cellular and Molecular Life Sciences. 74 (1 ...

*SLC23A2

Fischer H, Schwarzer C, Illek B (2004). "Vitamin C controls the cystic fibrosis transmembrane conductance regulator chloride ...

*RNF5

2006). "Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator". Cell. 126 ...

*1980s in science and technology

The gene responsible for the cystic fibrosis transmembrane conductance regulator was discovered. Mutations of the gene are ... considered causes of cystic fibrosis. The kakapo, a bird species of New Zealand, was termed a threatened species. The ...

*Mir-384 microRNA precursor family

"MicroRNA regulation of expression of the cystic fibrosis transmembrane conductance regulator gene". Biochemical Journal. 438 (1 ...

*ASIC3

... channel 3 and cystic fibrosis transmembrane conductance regulator". J. Biol. Chem. 281 (48): 36960-8. doi:10.1074/jbc. ... 2 hydrophobic transmembrane (TM) regions, and a large extracellular loop, which has many cysteine residues with conserved ...

*Channel blocker

Linsdell P, Hanrahan JW (November 1996). "Disulphonic stilbene block of cystic fibrosis transmembrane conductance regulator Cl ... Linsdell P (February 2014). "Cystic fibrosis transmembrane conductance regulator chloride channel blockers: Pharmacological, ... Cystic fibrosis is a progressive, genetic disease that is linked to CF transmembrane regulator (CFTR) dysfunction. Blockage of ... Cystic Fibrosis transmembrane regulators (CFTRs) function in chloride ion, bicarbonate anion, and fluid transport. They are ...

*DNAJC5

... has been shown to interact with the cystic fibrosis transmembrane conductance regulator. Mutations in this gene may ... 2006). "Cysteine string protein monitors late steps in cystic fibrosis transmembrane conductance regulator biogenesis". J. Biol ... "Cysteine string protein interacts with and modulates the maturation of the cystic fibrosis transmembrane conductance regulator ... It is known to play a role in cystic fibrosis and Huntington's disease. This protein has been proposed as a key element of the ...

*Sodium-hydrogen antiporter 3 regulator 1

1998). "An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton". J. Biol. ... 2000). "The PDZ-interacting domain of cystic fibrosis transmembrane conductance regulator is required for functional expression ... P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory ... "The cystic fibrosis transmembrane conductance regulator interacts with and regulates the activity of the HCO3- salvage ...

*Pyocyanin

"Regulation of the cystic fibrosis transmembrane conductance regulator ClK channel by its R domain". Journal of Biological ... aeruginosa to persist in the cystic fibrosis lung; it is often detected in the sputum from cystic fibrosis patients. Pyocyanin ... In the cystic fibrosis lung, intracellular pyocyanin converts molecular oxygen to the superoxide free radical by oxidizing ... Pseudomonas aeruginosa Cystic fibrosis Pyocyanin at Sigma-Aldrich Hassan H & Fridovich I (1980). "Mechanism of the antibiotic ...

*CFTR (disambiguation)

CFTR (cystic fibrosis transmembrane conductance regulator) is a membrane protein and chloride channel in vertebrates. CFTR may ...

*Single-nucleotide polymorphism

Cystic fibrosis caused by the G542X mutation in the cystic fibrosis transmembrane conductance regulator gene). rs6311 and ... β-thalassemia and cystic fibrosis result from SNPs. The severity of illness and the way our body responds to treatments are ... "Cystic fibrosis patients bearing both the common missense mutation Gly----Asp at codon 551 and the delta F508 mutation are ...

*Cystic fibrosis

"Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease". The ... cystic fibrosis transmembrane conductance regulator mRNA ameliorates the severity of pulmonary disease in cystic fibrosis". Am ... CF is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, ... "An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton". J. Biol. Chem. 273 ...

*Pancreatic disease

It is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The product of this gene ... The name cystic fibrosis refers to the characteristic 'fibrosis' (tissue scarring) and cyst formation within the pancreas, ... Cystic fibrosis, is a hereditary disease that affects the entire body, causing progressive disability and early death. ... EPI is found in humans afflicted with cystic fibrosis and Shwachman-Diamond syndrome. It is caused by a progressive loss of the ...

*Channel-conductance-controlling ATPase

Chen M, Zhang JT (1996). "Membrane insertion, processing, and topology of cystic fibrosis transmembrane conductance regulator ( ... In enzymology, a channel-conductance-controlling ATPase (EC 3.6.3.49) is an enzyme that catalyzes the chemical reaction ATP + ... The systematic name of this enzyme class is ATP phosphohydrolase (channel-conductance-controlling). As of late 2007, two ... This enzyme belongs to the family of hydrolases, specifically those acting on acid anhydrides to catalyse transmembrane ...

*STX8

"Syntaxin 8 impairs trafficking of cystic fibrosis transmembrane conductance regulator (CFTR) and inhibits its channel activity ... "Elevated expression of a regulator of the G2/M phase of the cell cycle, neuronal CIP-1-associated regulator of cyclin B, in ... McShea A, Samuel T, Eppel JT, Galloway DA, Funk JO (Jul 2000). "Identification of CIP-1-associated regulator of cyclin B (CARB ...

*GOPC

2005). "Interaction with cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) inhibits beta1-adrenergic ... Cystic fibrosis transmembrane conductance regulator and CSPG5. GRCh38: Ensembl release 89: ENSG00000047932 - Ensembl, May 2017 ... Cheng J, Wang H, Guggino WB (2004). "Modulation of mature cystic fibrosis transmembrane regulator protein by the PDZ domain ... chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator- ...

*CFTR inhibitory factor

... such as the cystic fibrosis transmembrane conductance regulator (CFTR), and P-glycoprotein by interfering with the host ... "Crystal structure of the cystic fibrosis transmembrane conductance regulator inhibitory factor Cif reveals novel active-site ... Secreted Protein PA2934 Decreases Apical Membrane Expression of the Cystic Fibrosis Transmembrane Conductance Regulator". ... By promoting the ubiquitin-mediated degradation of CFTR, Cif is able to phenocopy cystic fibrosis at the cellular level. The ...

*Congenital absence of the vas deferens

2007). "Molecular characterization of the cystic fibrosis transmembrane conductance regulator gene in congenital absence of the ... "The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel". J. Pediatr. 132 (4): 589- ... There are two main populations of CAVD; the larger group is associated with cystic fibrosis and occurs because of a mutation in ... Strikingly, CAVD is one of the most consistent features of cystic fibrosis as it affects 98-99% of individuals in this CF ...

*MicroRNA 138-1

... regulates expression and biosynthesis of wild-type and DeltaF508 mutant cystic fibrosis transmembrane conductance regulator". ...

*Allergic bronchopulmonary aspergillosis

"Frequency of cystic fibrosis transmembrane conductance regulator gene mutations and 5T allele in patients with allergic ... October 2003). "Allergic bronchopulmonary aspergillosis in cystic fibrosis-state of the art: Cystic Fibrosis Foundation ... ABPA should be suspected in patients with a predisposing lung disease-most commonly asthma or cystic fibrosis- and is often ... In people with predisposing lung diseases-such as persistent asthma or cystic fibrosis (or rarer diseases such as chronic ...

*Aminoglycoside

CF is caused by a mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In ... The aminoglycoside gentamicin has been used to treat cystic fibrosis (CF) cells in the laboratory to induce them to grow full- ... Pai VB, Nahata MC (October 2001). "Efficacy and safety of aerosolized tobramycin in cystic fibrosis". Pediatr. Pulmonol. 32 (4 ... 2003). "Gentamicin-Induced Correction of CFTR Function in Patients with Cystic Fibrosis andCFTRStop Mutations". New England ...

*STUB1

... inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator". ...

*Index of biochemistry articles

... cystic fibrosis transmembrane conductance regulator - cytochrome B - cytochrome C - cytochrome P-450 - cytochrome P-450 CYP1A1 ... Transmembrane ATPase - transmembrane helix - transmembrane protein - transmembrane receptor - transport protein - transport ...
Looking for online definition of cystic fibrosis transmembrane conductance regulator gene in the Medical Dictionary? cystic fibrosis transmembrane conductance regulator gene explanation free. What is cystic fibrosis transmembrane conductance regulator gene? Meaning of cystic fibrosis transmembrane conductance regulator gene medical term. What does cystic fibrosis transmembrane conductance regulator gene mean?
Provided herein are bioactive agents comprising a compound that inhibits the ion transport activity of a cystic fibrosis transmembrane conductance regulator (CFTR) and that is linked to a macromolecule that interacts with a cell that expresses CFTR. The bioactive agents described herein are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased CFTR activity, for example, secretory diarrhea.
Read "Interactions between Impermeant Blocking Ions in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore: Evidence for Anion-Induced Conformational Changes, The Journal of Membrane Biology" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
We wish to construct a mouse model for the human inherited disease cystic fibrosis. We describe here the successful targeting in embryonal stem cells of the murine homologue (Cftr) of the cystic fibrosis transmembrane conductance regulator gene, as the first critical step towards this end. The targeting event precisely disrupts exon 10, the site of the major mutation in patients with cystic fibrosis. The targeted cells are pluripotent and competent to form chimaeras.
We developed molecular models for the cystic fibrosis transmembrane conductance regulator chloride channel based on the prokaryotic ABC transporter, Sav1866. Here we analyze predicted pore geometry and side-chain orientations for TM3, TM6, TM9, and TM12, with particular attention being paid to the location of the rate-limiting barrier for anion conduction. Side-chain orientations assayed by cysteine scanning were found to be from 77 to 90% in accord with model predictions. The predicted geometry of the anion conduction path was defined by a space-filling model of the pore and confirmed by visualizing the distribution of water molecules from a molecular dynamics simulation. The pore shape is that of an asymmetric hourglass, comprising a shallow outward-facing vestibule that tapers rapidly toward a narrow bottleneck linking the outer vestibule to a large inner cavity extending toward the cytoplasmic extent of the lipid bilayer. The junction between the outer vestibule and the bottleneck features an
Cystic fibrosis transmembrane conductance regulator (CFTR) has been considered to be involved in the regulatory pathway of biliary mucin secretion. We investigated expression of CFTR protein and mRNA in 24 livers with hepatolithiasis, in 6 with cholangiocarcinoma, and in 12 histologically normal livers. According to the histologic features of chronic proliferative cholangitis, hepatolithiasis was subdivided into inflammatory cell infiltration predominant (N = 14) and fibrosis predominant (N = 10). The mean signal density of CFTR in overall hepatolithiasis and in histologically normal livers was 1.23 ± 0.15 and 1.01 ± 0.13, respectively (P | 0.05). The CFTR protein (1.60 ± 0.18) and mRNA (1.09 ± 0.15) in inflammatory cell infiltration predominant patients were significantly higher (CFTR protein, 1.01 ± 0.13; mRNA, 0.75 ± 0.11) than in control subjects (P | 0.05), whereas those in fibrosis-predominant patients (CFTR protein, 0.72 ± 0.15; mRNA, 0.55 ± 0.13) were less than in control subjects (P | 0
The olfactory epithelium (OE) of mice deficient in cystic fibrosis transmembrane conductance regulator (CFTR) exhibits ion transport deficiencies reported in human CF airways, as well as progressive neuronal loss, suggesting defects in olfactory neuron homeostasis. Microvillar cells, a specialized OE cell-subtype, have been implicated in maintaining tissue homeostasis. These cells are endowed with a PLCβ2/IP3 R3/TRPC6 signal transduction pathway modulating release of neuropeptide Y (NPY), which stimulates OE stem cell activity. It is unknown, however, whether microvillar cells also mediate the deficits observed in CFTR-null mice. Here we show that Cftr mRNA in mouse OE is exclusively localized in microvillar cells and CFTR immunofluorescence is coassociated with the scaffolding protein NHERF-1 and PLCβ2 in microvilli. In CFTR-null mice, PLCβ2 was undetectable, NHERF-1 mislocalized, and IP3 R3 more intensely stained, along with increased levels of NPY, suggesting profound alteration of the ...
Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis Academic Article ...
Structural information is required to define the molecular basis for chloride conduction through CFTR (cystic fibrosis transmembrane conductance regulator). Towards this goal, we expressed MSD2, the second of the two MSDs (membrane-spanning domains) of CFTR, encompassing residues 857-1158 in Sf9 cells using the baculovirus system. In Sf9 plasma membranes, MSD2 migrates as expected for a dimer in non-dissociative PAGE, and confers the appearance of an anion permeation pathway suggesting that dimeric MSD2 mediates anion flux. To assess directly the function and quaternary structure of MSD2, we purified it from Sf9 cells by virtue of its polyhistidine tag and nickel affinity. Reconstitution of MSD2 into liposomes conferred a 4,4′-di-isothiocyanostilbene-2,2′-disulphonate-inhibitable, chloride-selective electrodiffusion pathway. Further, this activity is probably mediated directly by MSD2 as reaction of its single cysteine residue (Cys866) with the thiol modifying reagent, ...
The level of the mature native 170 kDa form of CFTR (cystic fibrosis transmembrane conductance regulator) at the plasma membrane is under the control of a selective proteolysis catalysed by calpain. The product of this limited digestion, consisting of discrete fragments still associated by strong interactions, is removed from the plasma membrane and internalized in vesicles and subject to an additional degradation. This process can be monitored by visualizing the accumulation of a 100 kDa fragment in a proliferating human leukaemic T-cell line and in human circulating lymphocytes. In reconstructed systems, and in intact cells, the conversion of native CFTR into the 100 kDa fragment linearly correlated with calpain activation and was prevented by addition of synthetic calpain inhibitors. A reduction in Ca2+ influx, by blocking the NMDA (N-methyl-D-aspartate) receptor Ca2+ channel, inhibited the conversion of the native 170 kDa fragment into the 100 kDa fragment, whereas an endosome acidification ...
cAMP-Protein Kinase A Activates Cystic Fibrosis Transmembrane Conductance Regulator for ATP Release from Rat Skeletal Muscle during Low pH or Contractions. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Function and Expression of Cystic Fibrosis Transmembrane Conductance Regulator after Small Intestinal Transplantation in Mice. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Cystic fibrosis (CF) is a progressive life threatening multisystem genetic disease which affects the CF transmembrane conductance regulator channel. Respiratory causes remain the most common mortality in CF. With the onset of newborn screening, initiating treatments both for prophylaxis and disease management, optimizing nutritional support, and developing therapies targeting CF transmembrane conductance regulator protein, this has significantly changed the face of managing this devastating disease. Bronchoscopy and related procedures such as bronchoalveolar lavage (BAL), transbronchial biopsies, and protected brush sampling have been looked at in the management of CF as patients with CF continue to live longer with the help of newer therapies, the microbiome in the lung becomes less diverse along with increased occurrences for noninfectious causes of airway diseases ...
Cystic fibrosis (CF) lung disease is characterized by an inflammatory response that can lead to terminal respiratory failure. The cystic fibrosis transmembrane conductance regulator (CFTR) is mutated in CF, and we hypothesized that dysfunctional CFTR in platelets, which are key participants in immune responses, is a central determinant of CF inflammation. We found that deletion of CFTR in platelets produced exaggerated acute lung inflammation and platelet activation after intratracheal LPS or Pseudomonas aeruginosa challenge. CFTR loss of function in mouse or human platelets resulted in agonist-induced hyperactivation and increased calcium entry into platelets. Inhibition of the transient receptor potential cation channel 6 (TRPC6) reduced platelet activation and calcium flux, and reduced lung injury in CF mice after intratracheal LPS or Pseudomonas aeruginosa challenge. CF subjects receiving CFTR modulator therapy showed partial restoration of CFTR function in platelets, which may be a ...
The effects of a thiazolidinone derivative, 3-[(3-trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone (or CFTRinh-172), on cystic fibrosis transmembrane conductance regulator (CFTR) gating were studied in excised inside-out membrane patches from Chinese hamster ovary cells transiently expressing wild-type and mutant CFTR. We found that the application of CFTRinh-172 results in an increase of the mean closed time and a decrease of the mean open time of the channel. A hyperbolic relationship between the closing rate and [CFTRinh-172] suggests that CFTRinh-172 does not act as a simple pore blocker. Interestingly, the potency of inhibition increases as the open time of the channel is increased with an IC50 in the low nanomolar range for CFTR channels locked in an open state for tens of seconds. Our studies also provide evidence that CFTRinh-172 can bind to both the open state and the closed state. However, at least one additional step, presumably reflecting ...
J Biol Chem. 1995 Jan 27;270(4):1711-7. Comparative Study; Research Support, Non-U.S. Govt; Research Support, U.S. Govt, P.H.S.
Sigma-Aldrich offers abstracts and full-text articles by [Chatchai Muanprasat, Lalida Sirianant, Sunhapas Soodvilai, Ratchanaporn Chokchaisiri, Apichart Suksamrarn, Varanuj Chatsudthipong].
1CKY: Cystic fibrosis transmembrane conductance regulator: solution structures of peptides based on the Phe508 region, the most common site of disease-causing DeltaF508 mutation.
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EDITOR,-Cystic fibrosis is the most common serious autosomal recessive condition in white populations, affecting about 1 in 2500 live births, and until recently life expectancy rarely exceeded 30 years. The most common cystic fibrosis mutation (δF508, accounting for about 80% of two million British carriers), is a 3-bp deletion in a transmembrane protein cystic fibrosis transmembrane regulator gene. The next most common three or four mutations account for a further 5% of carriers.. One in 25 white people carries cystic fibrosis. As carriers are unaffected, individuals are often unaware until … ...
Many people with cystic fibrosis are counting on cystic fibrosis transmembrane conductance regulator modulators to improve their overall health. Im learning that they have effects I hadnt counted on.
Cystic fibrosis (CF) lung disease is characterized by chronic bacterial colonization and recurrent infection of the airways. Disruption of the cystic fibrosis transmembrane conductance regulator chloride channels in subjects with CF results in altered fluid and electrolyte transport across the airway epithelium thereby initiating infections.. These infections eventually destroy the lungs and contribute to significant morbidity and mortality in patients with CF. It is well known that antibacterial activity of innate immune mediators such as lysozyme and beta defensins in human airway surface liquid (ASL) is salt-sensitive; an increase in salt concentration inhibits their activity.. Conversely, their activity is increased by low ionic strength. Lowering the ASL salt concentration and increasing the ASL volume might therefore potentiate innate immunity and therefore decrease or prevent airway infections in subjects with CF.. Xylitol, a five-carbon sugar with low transepithelial permeability, which ...
Complex alleles in monogenic disease pose a challenge for clinicians because they are often associated with uncommon diagnostic and clinical features. Here we report on the 30 year course of a basic defect and disease in an individual with cystic fibrosis (CF) who was compound heterozygous for the cystic fibrosis transmembrane conductance regulator (CFTR) mutations R553X1 and the complex allele F508del-R553Q.2. The amino acid substitution R553Q resides within the ABC signature motif of CFTR.3 R553Q has been shown in heterologous model systems to partially correct the defective processing and anomalous ion channel gating of mutant F508del CFTR.4 Hence R553Q has been classified as a disease reverting suppressor mutation. Investigation of the affected subject, however, revealed a more complex manifestation of the basic defect of anomalous epithelial chloride conductance.. The sweat test is still the gold standard to diagnose CF5 whereby elevated sweat chloride concentrations of more than 60 mmol/l ...
Cystic Fibrosis (CF) is a progressive autosomal recessive disorder caused by defects in the cystic fibrosis transmembrane conductance regulator gene (CFTR). CFTR mutations cause loss or impairment of CFTR-mediated ion transport across epithelial cell membranes. CF affects many organs including the respiratory tract, pancreas, intestine, liver and the male reproductive tract. Liver disease occurs less frequently than pulmonary disease. CFTR is expressed in the bile duct epithelial cells and is responsible for the hydration of biliary secretions.. CF was until recently, thought to be a multi-organ disease. However, there are now recognized non-classical presentations of CF involving a few organs only and now there is well established data on single -organ involvement including Congenital Absence of the Vas Deferens and recurrent pancreatitis.. CF and PSC have several features in common. They both affect intrahepatic bile ducts by inspisated biliary secretions, chronic inflammation and fibrosis. Is ...
Ataluren (PTC 124; PTC Therapeutics),18 currently recognized as an orphan drug by the FDA, is a more appealing therapeutic option for class I CFTR defects. In a mechanism similar to the pleiotropic effects of aminoglycosides, ataluren allows ribosomes to read through the mRNA premature stop codons, resulting in the translation of complete CFTR proteins.19,20 Several phase II and III studies19-21 have evaluated this drugs efficacy and demonstrated improvements in nasal transepithelial potential differences, forced expiratory volume in 1 second (FEV1), and weight gain in both adult and pediatric patient populations.20 Adverse effects were generally mild, with gastrointestinal upset, headache, and dizziness most commonly reported (Table 2). Because of its efficacy in targeting the underlying cause of CF and favorable adverse effect profile, ataluren is considered the more appropriate initial approach compared with aminoglycosides in patients with CF who have class I mutations.10,21 Several phase ...
Background & Aims: Progressive liver disease is a severe complication of cystic fibrosis, a genetic disease characterized by impaired epithelial adenosine 3,5-cyclic monophosphate-dependent secretion caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). In the liver, CFTR is expressed in cholangiocytes and regulates the fluid and electrolyte content of the bile. Glibenclamide, a sulfonylurea and a known CFTR inhibitor, paradoxically stimulates cholangiocyte secretion. We studied the molecular mechanisms underlying this effect and whether glibenclamide could restore cholangiocyte secretion in cystic fibrosis. Methods: NRC-1 cells, freshly isolate rat cholangiocytes, isolated rat biliary ducts, and isolated biliary ducts from CFTR-defective mice (Cftr(tm1Unc)) were used to study fluid secretion (by video-optical planimetry), glibenclamide-induced secretion (by high-performance liquid chromatography in cell culture medium), intracellular pH and intracellular Ca2+ ...
Cystic fibrosis (CF) is an autosomal recessive disorder characterized by repeated and destructive lower respiratory infections, resulting in the gradual destruction of the lung tissue.[1]. The cause of CF is due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7.[2] The CFTR gene regulates chloride and sodium transport in the epithelial surfaces of the airway, pancreatic and biliary ducts, the gastrointestinal tract, sweat ducts and the vas deferens. Pathogenic mutations either remove or reduce the function of the CFTR gene.[3] This results in the production of sticky mucus build up and blockages that affect mainly the lungs, pancreas and sweat glands.. CF is an inherited condition that affects 1 in 2500 male or female Australian babies. All Australian babies are screened at birth for CF. Blood tests are carried out for the genetic testing of the CFTR gene and sweat tests are carried out to measure the amount of salt in the sweat. There is ...
In order to identify a possible hereditary predisposition to the development of obstructive pulmonary disease of unknown origin, we have looked for the presence of Cystic Fibrosis Transmembrane Regulator (CFTR) gene mutations in unrelated patients with no signs of Cystic Fibrosis (CF). We screened for 70 common mutations, and also for rare mutations by denaturing gradient gel electrophoresis analysis. In this search, different CFTR gene mutations (R75Q, delta F508, R1066C, M1137V and 3667ins4) were found in five out of 16 adult Italian patients with disseminated bronchiectasis, a significant increase over the expected frequency of carriers. Moreover, three rare CFTR gene DNA polymorphisms (G576A, R668C, and 2736 A--,G), not deemed to be the cause of CF, were found in two patients, one of which was a compound heterozygote with R1066C. These results indicate that CFTR gene mutations, and perhaps also DNA polymorphisms, may be involved in the etiopathogenesis of at least some cases of ...
Defects in cystic fibrosis transmembrane conductance regulator (CFTR) can cause cystic fibrosis (CF; MIM:602421), a common generalised disorder in Caucasians affecting the exocrine glands. CF results in an ionic imbalance that impairs clearance of secretions, not only in the lung, but also in the pancreas, gastrointestinal tract and liver. Wide-ranging manifestations of the disease include chronic lung disease, exocrine pancreatic insufficiency, blockage of the terminal ileum, male infertility and salty sweat. The class 3 mutations of CFTR such as G551D strongly decrease the time spent by CFTR in the open state (a gating defect). Results from 2-phase clinical trials using VX-770 (aka Ivacaftor), a CFTR potentiator, showed an increased CFTR channel open probability in G551D patients. Ivacaftor use showed improvements in CFTR and lung function of patients with at least one G551D allele (Accurso et al. 2010, Ramsey et al. 2011, Kapoor et al. 2014). In 2012, the FDA approved Ivacaftor (under the ...
Follow-up testing to identify mutations in individuals with a clinical diagnosis of cystic fibrosis (CF) and a negative targeted mutation analysis for the common mutations. Identification of mutations in individuals with atypical presentations of CF (eg, congenital bilateral absence of the vas deferens or pancreatitis). Identification of mutations in individuals where detection rates by targeted mutation analysis are low or unknown for their ethnic background. Identification of patients who may respond to cystic fibrosis transmembrane conductance regulator (CFTR) potentiator therapy. This is not the preferred genetic test for carrier screening or initial diagnosis. For these situations, order CFB / Cystic Fibrosis Mutation Analysis, 106-Mutation Panel. ...
The expression of cystic fibrosis transmembrane conductance regulator (CFTR) in the thyroid has not been documented to date, although a role for CFTR in the thyroid follicular epithelium is suggested both clinically, by the occurrence of subclinical hypothyroidism in patients with cystic fibrosis (CF), and physiologically, by the presence of low-conductance, adenosine 3,5-cyclic monophosphate-activated Cl channels in the follicular cells. Using reverse transcriptase-polymerase chain reaction with nested primers derived from exons 13 and 14 of the human CF gene, we have now documented the presence of CFTR mRNA in the human thyroid. Western blot analyses using six antibodies directed against different domains of human CFTR showed that a 165-kDa band was present in membrane extracts from bovine and human thyroid. This protein has the predicted size of mature CFTR and was not detected with preimmune serum or preadsorbed antiserum. By immunofluorescence and immunoperoxidase, CFTR was located in the ...
Small-molecule therapies that restore defects in cystic fibrosis transmembrane conductance regulator (CFTR) gating (potentiators) or trafficking (correctors) are being developed for cystic fibrosis (CF) in a mutation-specific fashion. Options for pharmacological correction of CFTR-p.Phe508del (F508del) are being extensively studied but correction of other trafficking mutants that may also benefit from ... read more corrector treatment remains largely unknown.We studied correction of the folding mutants CFTR-p.Phe508del, -p.Ala455Glu (A455E) and -p.Asn1303Lys (N1303K) by VX-809 and 18 other correctors (C1-C18) using a functional CFTR assay in human intestinal CF organoids.Function of both CFTR-p.Phe508del and -p.Ala455Glu was enhanced by a variety of correctors but no residual or corrector-induced activity was associated with CFTR-p.Asn1303Lys. Importantly, VX-809-induced correction was most dominant for CFTR-p.Phe508del, while correction of CFTR-p.Ala455Glu was highest by a subgroup of compounds ...
Purpose of review New therapeutics have been introduced for cystic fibrosis that modulate cystic fibrosis transmembrane conductance regulator (CFTR) function in a mutation-specific fashion. Despite CFTR genotype-based stratification of treatments, treatment efficacy is variable between study participants suggesting that individual factors further contribute to drug efficacy. Moreover, these treatments are ... read more licensed for a limited amount of CFTR mutations, and study participants with rare mutations that can potentially benefit from available treatments may be missed. New approaches that better support the identification of responders to CFTR modulators are, therefore, needed. Recent findings We, here, review how a patient-oriented research collaboration between basic and clinical scientists and a national cystic fibrosis patient organization led to the development of a CFTR-dependent assay using primary stem cell cultures termed intestinal organoids that can measure the individual ...
Cystic fibrosis (CF) remains the most common fatal hereditary lung disease. The discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene 25 years ago set the stage for: 1) unravelling the molecular and cellular basis of CF lung disease; 2) the generation of animal models to study in vivo pathogenesis; and 3) the development of mutation-specific therapies that are now becoming available for a subgroup of patients with CF. This article highlights major advances in our understanding of how CFTR dysfunction causes chronic mucus obstruction, neutrophilic inflammation and bacterial infection in CF airways. Furthermore, we focus on recent breakthroughs and remaining challenges of novel therapies targeting the basic CF defect, and discuss the next steps to be taken to make disease-modifying therapies available to a larger group of patients with CF, including those carrying the most common mutation ΔF508-CFTR. Finally, we will summarise emerging evidence indicating that acquired CFTR
TY - JOUR. T1 - A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases. AU - Lee, Ji Hyun. AU - Choi, Ji Ha. AU - Namkung, Wan. AU - Hanrahan, John W.. AU - Chang, Joon. AU - Song, Si Young. AU - Park, Seung Woo. AU - Kim, Dong Soo. AU - Yoon, Joo Heon. AU - Suh, Yousin. AU - Jang, In Jin. AU - Nam, Joo Hyun. AU - Kim, Sung Joon. AU - Cho, Mi Ook. AU - Lee, Jong Eun. AU - Kim, Kyung Hwan. AU - Lee, Min Goo. PY - 2003/9/15. Y1 - 2003/9/15. N2 - Aberrant membrane transport caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is associated with a wide spectrum of respiratory and digestive diseases as well as cystic fibrosis. Using a gene scanning method, we found 11 polymorphisms and mutations of the CFTR gene in the Korean population. Individual variants at these sites were analyzed by conventional DNA screening in 117 control and 75 patients having bronchiectasis or chronic pancreatitis. In a haplotype ...
Cystic fibrosis (CF) is an autosomal recessive disease that greatly diminishes life span owing to impaired function of the lungs and intestinal epithelia. Although the F508 homozygous mutation in the anion channel protein cystic fibrosis transmembrane conductance regulator (CFTR) is commonly found in CF patients, the mechanisms by which this mutation causes disease are unclear. To investigate this issue in vivo, Ostedgaard et al. generated pigs homozygous for CFTR-F508. Unlike previously established mouse models of CF, CFTR-F508 pigs develop airway and intestinal disease that closely resembles human CF pathology. In vivo studies agreed with previous results carried out in cell culture systems, and showed that the F508 mutation causes CFTR misfolding and degradation, and the failure of the protein to localise at the apical surface of epithelial cells. CFTR-F508 pigs provide a relevant model to further investigate mechanisms of CF pathogenesis and for testing therapies that aim to increase CFTR ...
Knowledge of cystic fibrosis transmembrane conductance regulator (CFTR) protein structure will contribute toward the understanding of CFTR function and CF biology, the mechanisms of action for CF drugs, and provide additional insight toward new drug discovery through structure-based drug design.
COLUMBIA, Mo. - A University of Missouri researcher believes his latest work moves scientists closer to a cure for cystic fibrosis, one of the worlds most common fatal genetic diseases.. The Journal of Biological Chemistry has published findings by Tzyh-Chang Hwang, a professor in the School of Medicines Department of Medical Pharmacology and Physiology and the Dalton Cardiovascular Research Center. The publication has been recognized as the "paper of the week" for the journal, meaning Hwangs work is considered to be in the top 1 percent of papers reviewed annually in terms of significance and overall importance.. Hwangs work focuses on the two most common genetic mutations among approximately 1,500 mutations found in patients with cystic fibrosis. These two mutations cause specific chloride channels in the cell, known as the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) chloride channels, to malfunction. This ultimately leads to repeated pneumonia, the primary cause of most ...
Cystic fibrosis (CF) is caused by loss-of-function mutations in the CF transmembrane conductance regulator (CFTR) Cl- channel. We developed a phenotype-based high-throughput screen to identify small-molecule activators of human airway epithelial Ca2+-activated Cl- channels (CaCCs) for CF therapy. Unexpectedly, screening of ~110,000 synthetic small molecules revealed an amino-carbonitrile-pyrazole, Cact-A1, that activated CFTR but not CaCC Cl- conductance. Cact-A1 produced large and sustained CFTR Cl- currents in CFTR-expressing Fisher rat thyroid (FRT) cells and in primary cultures of human bronchial epithelial (HBE) cells, without increasing intracellular cAMP and in the absence of a cAMP agonist. Cact-A1 produced linear whole-cell currents. Cact-A1 also activated ΔF508-CFTR Cl- currents in low temperature-rescued ΔF508-CFTR-expressing FRT cells and CF-HBE cells (from homozygous ΔF508 patients) in the absence of a cAMP agonist, and showed additive effects with forskolin. In contrast, VX-770 ...
We have used in situ hybridization to localize expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in the human gastrointestinal tract and associated organs. The stomach exhibits a low level of CFTR expression throughout gastric mucosa. In the small intestine, expression is relatively high in the mucosal epithelium, with a decreasing gradient of expression along the crypt to tip axis. The cells of the Brunners glands express high levels of CFTR mRNA. In addition, there is a small subpopulation of highly positive cells scattered along the epithelium in the duodenum and jejunum, but not in the ileum. These cells do not represent endocrine cells, as determined by lack of colocalization with an endocrine-specific marker. The distribution of CFTR mRNA in the colon is similar to the small intestine, with highest level of expression in the epithelial cells at the base of the crypts. In the pancreas, CFTR is expressed at high levels in the small, intercalated ducts and at ...
Gene expression is tightly regulated at the level of transcription through cooperation between cis-regulatory elements and trans-factors that bind to the regulatory elements. Together, these factors regulate the higher order chromatin structure which establishes domains that organize the genome and coordinate gene expression. However, the molecular mechanisms controlling transcription of individual loci within a topological domain (TAD) are not fully understood. The cystic fibrosis transmembrane conductance regulator (CFTR) gene provides a paradigm for investigating these mechanisms. CFTR occupies a TAD bordered by CTCF/cohesin binding sites within which are cell-type-selective cis-regulatory elements for the locus. We showed previously that intronic and extragenic enhancers, when occupied by specific transcription factors, are recruited to the CFTR promoter by a looping mechanism to drive gene expression. Here we use a combination of CRISPR/Cas9 editing of cis-regulatory elements and ...
Pathogenesis and treatment of cystic fibrosis; cystic fibrosis transmembrane conductance regulator (CFTR) function; infection, inflammation, and airway cell processes (e.g., ion transport, signaling) in disease; airway mucous and inhaled particle secretion; gene-editing; new research models ...
Histone deacetylase (HDAC) inhibitors have shown partial efficacy toward correcting cystic fibrosis transmembrane conductance regulator (CFTR) protein function in ΔF508- CFTR models. While current treatment options for CF generally concentrate on disease symptoms such as management of inflammation and bacterial infection, therapy using HDAC inhibitors has the potential to treat and correct the underlying etiology associated with the disorder. Subsequently, we have synthesized conformationally well-defined cyclic tetrapeptide derivatives based on the natural product HDAC inhibitor Apicidin, in order to formulate a pharmacophore model to describe and enhance the bioactivity of these molecules. Through this study we have developed HDAC inhibitors which improve CFTR trafficking from the endoplasmic reticulum (ER) while ultimately increasing ion conductance across the plasma membrane of a lung epithelial cell line expressing ΔF508-CFTR ...
GFP-tagged CFTR transgene is functional in the G551D cystic fibrosis mouse colon.: Trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR)
Its been known since the 1940s that CF was a genetic disease, but it wasnt until 1989 that the gene itself was identified as the cystic fibrosis transmembrane conductance regulator (CFTR). In healthy people with normal copies of this gene, the CFTR protein forms small pores on the surfaces of cells that open and close, allowing ions to flow in and out, thereby regulating the balance of salts and water. Different mutations to this gene cause different types of protein malfunctions: Some proteins crumple up and cant be transported to the cell surface. Others wont open and close properly. Some are left only half-built, and others get broken down too quickly. The result is CF.. Like most genes in the genome, we all inherit one copy of CFTR from mom, and the other from dad. People who inherit one mutated copy and one normal copy are called carriers. They are healthy (more or less - see the sidebar "The New Story About CF Carriers"), because their bodies get by on only half the normal amount of ...
Vertex Pharmaceuticals Inc. (Nasdaq: VRTX) announced positive data from a Phase 2 trial [1] of a second drug candidate, in addition to Kalydeco, aimed at treating cystic fibrosis. The company said it plans to start pivotal, or Phase 3, trials on VX-809 next year.. VX-809 was tested in combination with Kalydeco, or ivacaftor, a drug for which Vertex received approval earlier this year in both the U.S. [2] and in Europe for treatment of the most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, F508del. ...
There are two major diseases we focus on. The first is chronic rhinosinusitis (CRS), which affects 8-10% of the US population with direct healthcare costs of over 6 billion dollars annually. CRS has a major impact on individual quality of life as well as on public health; CRS accounts for 1 out of every 5 antibiotic prescriptions in adults in the US, making its treatment a major contributor to the emergence of antibiotic-resistant organisms. A continuing goal of our research is to identify new and better therapies to treat CRS and other airway diseases without the use of antibiotics, particularly through the stimulation of endogenous innate immune pathways. We also focus on cystic fibrosis (CF), the most common lethal genetic recessive disease in the US characterized by defective mucociliary transport due to altered ion transport and fluid secretion. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. Our goal is to better understand the ...
An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION ...
In CF, an abnormal gene called the cystic fibrosis transmembrane conductance regulator (CFTR) gene causes mucus to become thick and sticky. The mucus builds up in the lungs and blocks the airways, creating an environment that makes it easy for bacteria to grow. This leads to repeated serious lung infections that can damage your lungs ...
Recently, the Kim Lab has shown that the cystic fibrosis transmembrane conductance regulator (cftr) gene is responsible for mediating resistance to Pseudomonas aeruginosa in a zebrafish infection model. Using the Gene Expression Omnibus, an NCBI functional genomics data repository, it was determined that Smad3, a transcription factor in the TGF-β signaling pathway, is upregulated in the presence of P. aeruginosa. It was found that in our zebrafish model, the Smad3 paralogs Smad3a and Smad3b are upregulated following microinjection of a cftr antisense morpholino oligomer. It was also found that microinjection of Smad3a and Smad3b morpholinos, along with a Smad2 morpholino, and subsequent infection with Pseudomonas aeruginosa resulted in an increase in death, indicating that Smad3 has a protective effect against infection.
Cystic fibrosis - In cystic fibrosis, the gene that manufactures the protein called cystic fibrosis transmembrane conductance regulator is damaged. According to Encyclopedia Britannica: The defect (or mutation) found in the gene on chromosome 7 of persons with cystic fibrosis causes the production of a protein that lacks the amino acid phenylalanine. This flawed protein somehow distorts the movement of salt and water across the membranes that line the lungs and gut, resulting in dehydration of the mucus that normally coats these surfaces. The thick, sticky mucus accumulates in the lungs, plugging the bronchi and making breathing difficult. This results in chronic respiratory infections, often with Staphylococcus aureus or Pseudomonas aeruginosa. Chronic cough, recurrent pneumonia, and the progressive loss of lung function are the major manifestations of lung disease, which is the most common cause of death of persons with cystic fibrosis. ...
Membrane, Mutations, Cystic Fibrosis, Fibrosis, Mutation, ATP, Endoplasmic Reticulum, Reticulum, Chloride Channel, Disease, Cystic Fibrosis Transmembrane Conductance Regulator, Cells, Retention, Atpase, Cftr Protein, Epithelial Cells, Phosphorylation, Proteins, Role, Cell
This chapter reviews the well-characterized genetic syndromes of bacterial susceptibility with an eye toward specificity of the susceptibility, applicability of the defect to infections in the general population, and, where applicable, treatment. Defects in barriers involving the skin and lung and defects of leukocyte number, trafficking, and function are also considered in this chapter. The major protection afforded by the skin is due to the stratum corneum, which provides a multifunctional barrier retarding water loss and providing an antimicrobial barrier. Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), the gene that encodes the major epithelial chloride channel. This chapter focuses on examples of innate immune defects, especially those involving phagocytic cells as mutations in the genes regulating the innate immune system have been very informative regarding the specific associations of genes and
Basal defekt Indtil videre er der kun tre præparater på markedet, som virker ved at modulere den defekte Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) -kanal. Det første stof, ivacaftor, virker på såkaldte "gating-mutationer", hvor CFTR-kanalen er til stede i cellevæggen, men ikke fungerer normalt. Ivacaftor åbner kanalen, som dermed opnår funktion. Der er vist eklatant effekt på lungefunktion (10% stigning), trivsel og endda korrektion af sved-klorid til normale værdier. Præparatet er i Europa kun godkendt til patienter med disse mutationer, hvoraf der kun er få (< 10) i Danmark. Flere mutationer, som godkendes udenfor Europa, forventes at komme til. Det andet præparat er en kombinationsbehandling (lumacaftor/ivacaftor) med dels korrigerende, dels potentierende (som ved ivacaftor) effekt på patienter med to deltaF508 mutationer (75% af danske CF patienter). Effekten af denne behandling er ikke så eklatant på lungefunktion (stigning på 3%) som ivacaftor til ...
囊狀纖維化(CF)是一種遺傳性的基因突變疾病,屬於體染色體隱性遺傳,在白種人較為常見,帶因比例約為3%,發病率約為1/3300,而其中亞裔僅佔1/32000。近年來,隨著國人與外籍人士通婚比例增加,可能提高此遺傳疾病之發生率,但目前仍然屬於國內十分罕見的疾病之一。. 囊狀纖維化的基因突變位在第七對染色體長臂 7q31.2 區域的鹼基對上,進而導致人體中特定蛋白功能的缺陷,這些蛋白被稱為「囊狀纖維化跨膜傳導調節節因子」(CFTR, cystic fibrosis transmembrane conductance ...
Zkratka CFTR označuje speciální buněčný membránový receptor (cystic fibrosis transmembrane conductance regulator), který je určen genem stejného názvu, a který je zodpovědný za transport molekul chloru mezi buňkou a okolím. Mutace v CFTR genu mohou způsobit vznik cystické fibrózy ...
Abstract: "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Cystic fibrosis is a monogenic recessive disorder founds predominantly in caucasian population causes exocrine glands function defect. This disease arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. ...
The opportunistic pathogen Pseudomonas aeruginosa secretes a protein that triggers the accelerated degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) in airway epithelial cells. This protein, known as the CFTR inhibitory factor (Cif), acts as a virulence factor, and may facilitate airway colonization by P. aeruginosa. The objective of this investigation was to elucidate the mechanism by which this bacterial protein mediates its effects on mammalian cells. Initial sequence analysis suggested that Cif is an epoxide hydrolase (EH), but its sequence violates two strictly conserved EH motifs. To investigate the mechanistic basis of Cif activity, we have determined its structure to a 1.8 � resolution limit by X-ray crystallography. The catalytic triad consists of residues Asp129, His297, and Glu153, which are conserved across the family of EHs. At other positions, sequence deviations from canonical EH active-site motifs are stereochemically conservative. Comparison of Cif ...
SWISS-MODEL Template Library (SMTL) entry for 1r0x. Cystic fibrosis transmembrane conductance regulator (CFTR) nucleotide-binding domain one (NBD1) with ATP
Adapter protein that functions as clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containing non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Involved in CFTR trafficking to the late endosome. Involved in several receptor-mediated
84 98. Li, J.P. et al. Interleukin 27 as a negative regulator of human neutrophil function. Scand J Immunol 72 284 292 (2010). 99. Zhu, S., Lee, D.A. & Li, S. IL 12 and IL 27 sequential gene therapy via intramuscular electropor ation delivery for eliminating distal aggressive tumors. J Immunol 184 2348 2354 (2010). 100. Batten, M. et al. Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17 producing T cells. Nat Immunol 7 929 936 (2006). 101. Stumhofer, J.S. et al. Interleukin 27 negatively regulates the development of interleukin 17 producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol 7 937 945 (2006). 102. Flotte, T.R. et al. Stable i n vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno associated virus vector. Proc Natl Acad Sci U S A 90 10613 10617 (1993). 103. Conrad, C.K. et al. Safety of single dose administration of an adeno associated virus (AAV) CFTR vector in ...
Carbonic anhydrase 12 is an enzyme that in humans is encoded by the CA12 gene. Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. This gene product is a type I membrane protein that is highly expressed in normal tissues, such as kidney, colon and pancreas, and has been found to be overexpressed in 10% of clear cell renal carcinomas. Two transcript variants encoding different isoforms have been identified for this gene. Loss of function mutations in the CAXII gene result in defects in fluids and carbonate secretions in the following diseases: 1) Cystic fibrosis-like syndrome with normal cystic fibrosis transmembrane conductance regulator (CFTR) protein levels 2) Pancreatitis 3) Sjögrens syndrome 4) Xerostomia or ...
Calderon, D. P., Fremont, R., Kraenzlin, F., & Khodakhah, K. (2011). The neural substrates of rapid-onset Dystonia-Pakrinsonism. Nature Neuroscience, 14, 357-365. doi: 10.1038/nn.2753. Clapham, D. E. (2007). Calcium signaling. Cell, 131(6): 1047-1058. doi: 10.1016/j.cell.2007.11.028. de Carvalho Aguiar, P., Sweadner, K. J., Penniston, J. T., Zaremba, J., Liu, L., Caton, M., Linazasoro, G., Borg, M., Tijssen, M. A. J., Bressman, S. B., Dobyns, W. B., Brashear, A., & Ozelius, L. J. (2004). Mutations in the Na/K-ATPase 3 Gene ATP1A3 are associated with rapid-onset Dystonia Parkinsonism. Neuron, 43(2), 169-175. http://ac.els-cdn.com.myaccess.library.utoronto.ca/S089662730400399X/1-s2.0-S089662730400399X-main.pdf?_tid=c18d5f6a-b806-11e5-ae23-00000aacb35d&acdnat=1452477666_6c4215a4b79cf23c18901269a0763211. Guo, Y., Su, M., McNutt, M. A., & Gu, J. (2009). Expression and Distribution of Cystic Fibrosis Transmembrane Conductance Regulator in Neurons of the Human Brain. Journal of Histochemistry and ...
Functional expression of cystic fibrosis transmembrane conductance regulator in rat oviduct epithelium (pages 864-872). Minhui Chen, Jianyang Du, Weijian Jiang, Wulin Zuo, Fang Wang, Manhui Li, Zhongluan Wu, Hsiaochang Chan and Wenliang Zhou. Version of Record online: 17 OCT 2008 , DOI: 10.1111/j.1745-7270.2008.00469.x. ...
TY - JOUR. T1 - Regulation of cholangiocyte secretion. AU - Fitz, J. Gregory. PY - 2002/8. Y1 - 2002/8. N2 - Observations from a variety of model systems suggest that ductular bile formation is mediated in large part by transepithelial transport of Cl- ions and have identified Cl- channels in the apical membrane as important targets for hormones and other factors that modulate bile volume and composition through effects on duct cells. Signaling through secretin receptors that stimulate adenylyl cyclase and activate the cystic fibrosis transmembrane regulator (CFTR) Cl- channels represents a prototype for cholangiocyte secretion. However, recent observations indicate that cholangiocytes also express a variety of receptors that modulate secretory responses in the absence of effects on cyclic adenosine monophosphate (cAMP), and Cl- channels unrelated to CFTR have been identified. Moreover, rapid exocytosis of subapical vesicles is coupled closely to different Cl- secretory responses. These ...
Introduction: Irelands Cystic Fibrosis (CF) newborn screening programme is due to commence later in 2011 using immune reactive trypsinogen & genetic analysis for the detection of cystic fibrosis transmembrane regulator protein (CFTR) mutations. The National Centre for Medical Genetics screens for 11 CFTR mutations & further analysis for rarer mutations is currently performed in Manchester (using gene sequencing & multiplex ligation-dependant probe amplification (MLPA) testing). Prior to 2008 this further analysis was performed in Exeter & subsequently in Brest.. Aim: To identify the turn-around time for genetic analysis results for children with suspected CF. Methods: A 16 year retrospective study of genetic analysis results for CFTR mutations was performed. The turn-around time was defined as the number of days from sending DNA until reports were received. Descriptive statistics were used.. Results: Overall, the median time to receive genetic analysis results was 23 days, range 1-2434 days ...
US scientists have created pigs with cystic fibrosis (CF), a breakthrough that should open the door to a raft of research into the fatal condition.. Initial reports from the study, published in the journal Science, suggest that the pig model is manifesting a number of the early markers for the disease: an abnormal pancreas, liver and gall bladder and meconium ileus (an inability to pass faeces in a newborn) - the first animal model to do so, although no abnormal lung function has yet been detected.. CF affects 8000 people in the UK, and is caused by the inheritance of a mutated version of a gene called CFTR (cystic fibrosis transmembrane regulator) that codes for chloride ion channels important in the production of mucus, sweat and digestive juices. Both copies of the CFTR gene must be mutated for the disease to be present. Prolonged inappropriate production of these vital secretions leads to poor growth, recurrent lung inflammation and infection, progressive disability and multi-system ...
Background: It has been suggested that low mu M concentrations of S-nitrosoglutathione (GSNO), an endogenous bronchodilator, may promote maturation of the defective cystic fibrosis (CF) transmembrane conductance regulator ( CFTR). Because nitric oxide ( NO) and GSNO levels appear to be low in the CF airway, there is an interest in the possibility that GSNO replacement could be of therapeutic benefit in CF.. Methods: The effect of GSNO on chloride (Cl-) transport was investigated in primary nasal epithelial cells obtained from CF patients homozygous for the delF508 mutation, as well as in two CF cell lines (CFBE and CFSME), using both a fluorescent Cl- indicator and X-ray microanalysis. Maturation of delF508 CFTR was determined by immunoblotting.. Results: Treatment with 60 mu M GSNO for 4 hours increased cAMP-induced chloride efflux in nasal epithelial cells from 18 out of 21 CF patients, but did not significantly affect Cl- efflux in cells from healthy controls. This Cl- efflux was confirmed by ...
Cystic fibrosis (CF), a common inherited disease, is caused by mutations in the gene CF transmembrane conductance regulator (CFTR). This gene encodes the CFTR protein, which is located on the apical surface of the epithelial cells and has many functions, the most important of which is thought to be ion transport. Abnormal ion transport leads to accumulation of thick secretions in the airways, infection, inflammation and eventually irreversible lung damage. There is currently no treatment that has been demonstrated to halt the natural progression of the disease; all available successful therapies merely slow down the rate of decline in clinical condition, which still leads to premature death. The first therapy to target the CFTR defect directly has recently been approved in the USA and the European Union: treatment with ivacaftor (marketed as Kalydeco) resulted in significant improvements in lung function, exacerbation rate, weight gain and quality of life in patients with the G551D mutation.1 ...
null pigs provide a relevant model to test gene therapy vectors. Using an in vivo selection strategy that amplifies successful capsids by replicating their genomes with helper adenovirus coinfection, we selected an adeno-associated virus (AAV) with tropism for pig airway epithelia. The evolved capsid, termed AAV2H22, is based on AAV2 with 5 point mutations that result in a 240-fold increased infection efficiency. In contrast to AAV2, AAV2H22 binds specifically to pig airway epithelia and is less reliant on heparan sulfate for transduction. We administer AAV2H22-CFTR expressing the CF transmembrane conductance regulator ...
E coli FtsE protein: Cell division ATP-binding protein; conditionally lethal missense substitutions in this protein are similar to those found in the cystic fibrosis transmembrane conductance regulatory protein (CFTR) of human patients; partial amino acid sequence given in first source; homologous proteins found in other bacterial species
Abstract Cystic fibrosis (CF) is a life-limiting disease caused by mutations in the human CFTR gene, encoding an anion-selective channel. Because CF-causing mutations affect both CFTR permeation/gating and biogenesis, multi-assay approaches have been implemented in drug development, sequentially screening for channel function and membrane density. Here we present the first assay capable of simultaneous assessment of both CFTR characteristics. Images of live HEK293 cells co-expressing a soluble and a CFTR-tagged fluorescent protein are analysed to quantify both CFTR membrane density and ion channel function. We monitor F508del-CFTR, the most common disease-causing mutant. Furthermore, we characterize a panel of 62 CF-causing mutations and profile effects of acute treatment with approved drug VX-770, mapping potentiation on CFTR structures. We validate our assay by confirming F508del-CFTR rescue by incubation at low temperature, treatment with CFTR-targeting drugs and introduction of second-site ...
|p|VX-809 is a CFTR corrector that partially restores the function of F508del-CFTR. In Fischer rat thyroid (FRT) cells, it increases F508del-CFTR maturation at EC50 of 0.1 μM, and elevates F508del-CFTR-mediated chloride transport at EC50 of 0.5 μM [1]. It
Membrane Protein Disease, Innate Immunity. Plasma membrane (PM) proteins including signaling receptors, ion channels and transporters play crucial roles in physiological functions of cells and organisms. Genetic and environmental stresses cause the defective expression of PM proteins that is associated with several human diseases such as cystic fibrosis (CF). The ultimate goal in our research is to elucidate the molecular and cellular mechanisms underlying the defective expression of PM proteins and to help develop novel therapeutic approaches for human diseases.. Right now, we focus on the CFTR chloride channel associated with CF, one of the most common genetic diseases in Caucasians. While the most common CFTR mutant in CF patients has the ability to function as a chloride channel, it is rapidly eliminated by proteolysis through cellular quality control systems including the PM quality control mechanism that we originally identified. We are interested in understanding the molecular and ...
VX 661 | CFTR corrector | VX661 | CAS [1152311-62-0] | Axon 2169 | Axon Ligand™ with >99% purity available from supplier Axon Medchem, prime source of life science reagents for your research
CF develops as a effect of several factors where mutants cause: failure to clear mucose secernments, a dearth of H2O in mucose secernments, an elevated salt content of perspiration and other secernments, and chronic infection limited to the respiratory piece of land. In the respiratory piece of land inordinate sums of Na are absorbed through CF epithelial cells and signal is mediated, as cells are unable to release chloride ions in response to cyclic adenosine monophosphate ( camp ) . These effects are traced to CFTR defects ( Figure 1 ) . Six categories of CFTR mutants are identified: I category - the absence of synthesis ; II category - faulty protein ripening and premature debasement ; III category - broken ordinance, for case diminished ATP binding and hydrolysis ; IV category - faulty chloride conductance or channel gating ; V category - a decreased figure of CFTR transcripts due to a booster or splicing abnormalcy ; VI category - accelerated turnover from the cell surface [ KW1 ] . ...
Growing evidence suggests functional interaction between CFTR and P2YR. P2Y2R can regulate CFTR activity in different systems (Paradiso et al., 2001; Marcet et al., 2003). Here, we extend these findings by showing that CFTR modulates the P2Y1R signaling pathway. We report that CHO cells express, in addition to P2Y2R (Marcet et al., 2003), the P2Y1R subtype, which does not regulate CFTR activity in CHO-BQ1 cells. Moreover, we show that, in CHO cells, the expression of the recombinant CFTR (CHO-BQ1), but not the expression of the vector alone (CHO-KNUT), causes an apparent switch in the G-protein-coupling of P2Y1R from a Gq/11- to Gi/o-type. This change in G-protein selectivity was specific of P2Y1R since P2Y2R G-protein-coupling remained unaffected by CFTR.. Our findings that the P2Y1R antagonist MRS2179 and the P2Y1R knockdown antisense experiments abolished the ADP-induced Ca2+ response strongly suggest that putative hamster homologous of human P2Y12- or P2Y13-Gi protein-coupled receptors are ...
Cystic fibrosis is the most common life-threatening inherited disease in the UK. We study the protein whose dysfunction causes cystic fibrosis, CFTR. This same protein is responsible for the excessive salt/water loss occurring during secretory diarrhoeas (e.g. cholera). CFTR belongs to the superfamily of ABC proteins, which couple hydrolytic cycles at conserved nucleotide-binding domains (NBDs) to diverse cellular functions. CFTR is unique among ABC proteins in that its transmembrane domains comprise an ion channel. Opening and closing (gating) of the ion-permeation pathway is "remotely" controlled by ATP binding and hydrolysis at its NBDs . With our experiments we aim at deepening our understanding of how CFTR works, setting foundations for pharmacological alteration of its activity. In addition, by allowing us to uniquely track conformational changes affecting the ion-permeation pathway, our CFTR studies may help better understand conserved ABC mechanisms. ...
A Prospective Study to Evaluate Biological and Clinical Effects of Significantly Corrected CFTR Function (the PROMISE Study) (PROMISE-OB-18 ...
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What is Gene Therapy? (2008): CF gene therapy aims to insert a fully functional CFTR gene into the lung airway cells of people with the condition. Two main types of vector are used to deliver this new copy of the gene. A viral vector, engineered from viral particles or non-viral vectors, plasmid DNA molecules condensed by other chemical entities. More.... ...
Gavins mutations are G551D and Df508. Both are currently being studied in clinical trials for two therapies that are designed to correct the function of the defective CFTR protein made by the CF gene (his mutations), allowing chloride and sodium (salt) to move properly in and out of cells lining the lungs and other organs. If these medications make it through the clinical trials they will allow Gavin to live a much more "normal" life ...
Gavins mutations are G551D and Df508. Both are currently being studied in clinical trials for two therapies that are designed to correct the function of the defective CFTR protein made by the CF gene (his mutations), allowing chloride and sodium (salt) to move properly in and out of cells lining the lungs and other organs. If these medications make it through the clinical trials they will allow Gavin to live a much more "normal" life ...
Abstract Background Cystic fibrosis (CF) is caused by mutations in the CFTR gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic ...
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In this study we found that there was a deficit of GSH in the airways of young children with CF compared to disease controls. Our results are in accord with the seminal investigation that highlighted a systemic deficiency of GSH in young adults with CF [11]. Thus, our data demonstrate that GSH is low in the ELF of individuals with CF from an early age. This deficiency will make the lungs of these children more vulnerable to oxidative stress over the course of their disease. Our findings differ from those in an earlier study that showed GSH levels were not significantly lower in infants and young children with CF [25]. The different results probably reflect the greater power in our study and that our method for quantification of GSH is superior to what was available at the time of the previous work.. Since the discovery that patients with CF have a systemic deficiency in GSH, it has been argued strongly that this deficit results directly from an inability of a defective CFTR to transport GSH ...
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Plasma membrane Cl- channels perform a variety of functions, including control of excitability in neurons and muscle, cell volume regulation and transepithelial transport. Structurally, three classes of Cl- channels have been identified: ligand-gated, postsynaptic Cl- channels (e.g. GABA and glycine receptors); the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels (which belong to the traffic ATPase superfamily); and the CLC family of Cl- channels. Recent developments of note include further characterization of the expanding CLC Cl- channel family, advances in understanding the regulation of the CFTR Cl- channel and its emergent role as a regulator of other channels, clarification of issues related to swelling-activated Cl- channels, and the discovery that several co-transporter molecules are now known to induce Cl- currents in Xenopus oocytes.. ...
The deletion of phenylalanine 508 in the first nucleotide binding site from the cystic fibrosis transmembrane conductance regulator is directly connected with >90% of cystic fibrosis cases. some misfolding and suppressor mutations in the nucleotide binding and transmembrane domains had been evaluated for results for the folding and maturation from the proteins. The outcomes indicate how the isolated NBD1 responds to both ΔF508 mutation and intradomain suppressors of the mutation. Furthermore identification of the book second site suppressor from the defect within the next transmembrane site shows that ΔF508 also results interdomain interactions crucial for later on measures in the biosynthesis of CFTR. folding stability or efficiency. Alternatively they could alter the discussion of CFTR domains while departing the biochemical and biophysical properties from the isolated NBD unaltered. The suppressors may also possess little influence for the properties from the CFTR polypeptide in but may ...
Optimal fetal lung growth requires anion-driven fluid secretion into the lumen of the developing organ. The fetus is hypercalcemic compared to the mother and here we show that in the developing human lung this hypercalcaemia acts on the extracellular calcium-sensing receptor, CaSR, to promote fluid-driven lung expansion through activation of the cystic fibrosis transmembrane conductance regulator, CFTR. Several chloride channels including TMEM16, bestrophin, CFTR, CLCN2 and CLCA1, are also expressed in the developing human fetal lung at gestational stages when CaSR expression is maximal. Measurements of Cl−-driven fluid secretion in organ explant cultures show that pharmacological CaSR activation by calcimimetics stimulates lung fluid secretion through CFTR, an effect which in humans, but not mice, was also mimicked by fetal hypercalcemic conditions, demonstrating that the physiological relevance of such a mechanism appears to be species-specific. Calcimimetics promote CFTR opening by ...
Approximately 30,000 people in the United States have been diagnosed with CF, which affects both males and females. Its not contagious, so you cant catch CF from another person.. Cystic fibrosis is an inherited disease caused by mutations (changes) in a gene on chromosome 7, one of the 23 pairs of chromosomes that children inherit from their parents. CF occurs because of mutations in the gene that makes a protein called CFTR (cystic fibrosis transmembrane regulator). A person with CF produces abnormal CFTR protein - or no CFTR protein at all, which causes the body to make thick, sticky mucus instead of the thin, watery kind.. People who are born with CF have two copies of the CF gene. In almost all people born with CF, one gene is received from each parent. This means that the parents of kids with CF are usually both CF carriers - that is, they have one normal and one defective gene - but the parents may not have CF themselves because their normal gene is able to "take over" and make the ...
Background: Nasal potential difference (NPD) test has long been used to assist in the diagnosis of Cystic Fibrosis (CF) and more recently as an outcome measure in clinical trials of new CF therapies. This test has also been adapted to the mouse nose. Objectives: We aimed at evaluating variability of the NPD measurements in CF patients displaying two severe CFTR mutations and in sex-matched healthy controls. NPD recorded from F508del-CF and normal wild-type mice were also compared. Methods and results: In each setting, tests were performed by a single qualified operator. In the clinical setting, the latest standardized operation protocol of the CF foundation was followed. A total of 80 tracings were obtained from 10 patients (23.2 y; range 14 to 32) and 10 healthy subjects (34 y; range 24 to 53), each tested twice, in both nostrils. Two CF and two controls were excluded from the statistical data analysis due to the presence of a single non interpretable NPD tracing (4/80, 5%). To achieve equal sample
Cystic Fibrosis Overview What is cystic fibrosis? Cystic fibrosis (CF) is an inherited disease characterized by an abnormality in the bodys salt, water- and mucus-making cells. It is chronic, progressive, and is usually fatal. In general, children with CF live into their 30s. Children with CF have an abnormality in the function of a cell protein called the cystic fibrosis transmembrane regulator (CFTR). CFTR controls the flow of water and certain salts in and out of the bodys cells. As the movement of...
Title:Rescuing Mutant CFTR: A Multi-task Approach to a Better Outcome in Treating Cystic Fibrosis. VOLUME: 19 ISSUE: 19. Author(s):Margarida D. Amaral and Carlos M. Farinha. Affiliation:BioFiG - Center for Biodiversity, Functional and Integrative Genomics, Department of Chemistry & Biochemistry, Faculty of Sciences, University of Lisboa, Campo Grande, C8 bdg, 1749-016 Lisboa, Portugal.. Keywords:Cystic fibrosis, F508del-CFTR, rescue, correctors, potentiators, endoplasmic reticulum retention, traffic mutant, misfolding protein.. Abstract:Correcting multiple defects of mutant CFTR with small molecule compounds has been the goal of an increasing number of recent Cystic Fibrosis (CF) drug discovery programmes. However, the mechanism of action (MoA) by which these molecules restore mutant CFTR is still poorly understood, in particular of CFTR correctors, i.e., compounds rescuing to the cells surface the most prevalent mutant in CF patients - F508del-CFTR. However, there is increasing evidence that to ...
Mature three-spined stickleback males use spiggin threads secreted from their kidney to glue together nest material. This requires strongly hypertrophied renal proximal tubular cells, which compromises renal osmoregulatory function during the breeding period. Experimental evidence suggests that the intestine takes over hypotonic fluid secretion at that stage but the mechanism is unexplored. To unravel the molecular mechanism we analyzed and compared transcript levels of several membrane proteins involved in water and salt transport in intestinal and renal tissues, in non-mature males (NM), mature males (MM), and mature females (MF). Aquaporin paralogs aqp1a, -30, -8aa, -8ab, -10a, and -10b, two Na+,K+-ATPase alpha-1 subunit isoforms (nka547, nka976), Na+,K+,2C1(-)-, and Na+,CI--cotransporters (nkcc1a, nkcc2,ncc), the cystic fibrosis transmembrane conductance regulator (cftr) and two claudin isoforms (cldn2, cldn15a) were expressed in the intestine and kidney in all groups. There were no ...
TY - JOUR. T1 - A cluster of cystic fibrosis mutations in exon 17b of the CFTR gene. T2 - A site for rare mutations. AU - Mercier, B.. AU - Lissens, W.. AU - Novelli, G.. AU - Kalaydjieva, L.. AU - De Arce, M.. AU - Kapranov, N.. AU - Canki Klain, N.. AU - Estivill, Xavier P.. AU - Palacio, Ana. AU - Cashman, S.. AU - Savov, A.. AU - Audrézet, M. P.. AU - Dallapicolla, B.. AU - Liebaers, I.. AU - Quéré, I.. AU - Raguénès, O.. AU - Verlingue, C.. AU - Férec, C.. PY - 1994/9. Y1 - 1994/9. N2 - Intensive screening has improved our understanding of the profile of mutations in the CFTR gene in which more than 400 mutations have been detected to date. In collaboration with several European laboratories we are involved in such analysis. We have identified 14 new mutations in exon 17b of CFTR, having analysed 780 CF chromosomes, and have compared the frequency of mutations in this exon with that of other regions of the CFTR gene. The results obtained indicate an accumulation of mutations, not only ...
Welcome to the Cystic Fibrosis Mutation Database (CFTR1), devoted to the collection of mutations in the CFTR gene for the international cystic fibrosis genetics research community. It was initiated by the Cystic Fibrosis Genetic Analysis Consortium in 1989 to increase and facilitate communications among CF researchers, and is maintained by the Cystic Fibrosis Centre at the Hospital for Sick Children in Toronto. The specific aim of the database is to provide up to date information about individual mutations in the CFTR gene. In a major upgrade in 2010, all known CFTR mutations and sequence variants have been converted to the standard nomenclature recommended by the Human Genome Variation Society. In addition, an on-line process for the submission of new mutations has been added. While we will continue to ensure the quality of the data, we urge the international community to give us feedback and suggestions. Please send email to cftr.admin ...
Cystic fibrosis (CF) is a multi-organ autosomal recessive disease of fluid-transporting epithelia, due to a mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR is a cAMP-regulated Cl-channel involved in various regulatory processes. Salt and water transport depend on CFTR and the epithelial sodium channel (ENaC), operating in concert with the paracellular pathway through the tight junctions (TJ). The ionic composition of the ASL has been assumed to be altered in CF, resulting in a fatal accumulation of viscous mucus in the airways.. ASL samples were collected from tracheal and nasal fluid in normal and transgenic CF mice and from the fluid covering the apical surface of normal bronchial cells (16HBE14o-) and a CF human bronchial cell line (CFBE41o-). Analysis of the elemental content of the ASL was performed by X-ray microanalysis. The ASL contained more Na and Cl in CFTR-deficient or DF508-CFTR-containing cells than in control cells with ...
Recently, Schwartzs group in Manchester and Cohnet al from Duke University Medical Center, Durham, have described associations between mutant CFTR alleles1 and chronic pancreatitis. In the former study 18 (13.4%) of 134 patients had CFTR mutations on one chromosome and in the latter 10 (37%) of 27 patients with idiopathic chronic pancreatitis had at least one abnormal CFTR allele. This compares with an expected gene frequency of 5.3%. In four and three patients, respectively, both alleles were affected; however, none had lung disease suggestive of cystic fibrosis nor typical sweat electrolyte abnormalities. Both studies identified patients with the 5T allele, a mutation in the non-coding sequence of thymidine residues on intron 8 which leads to a reduction in mRNA and low levels of CFTR protein. Homozygotes or compound heterozygotes with this mutation often have congenital bilateral absence of the vas deferens (CBAVD) and infertility.. Can these patients be considered to have cystic fibrosis? ...
Abnormalities in autonomic function in obese boys at-risk for insulin resistance and obstructive sleep apnea Pediatr Res. 2019 May; 85(6):790-798. . View in PubMed. Congenital central hypoventilation syndrome: diagnosis and management Expert Rev Respir Med. 2018 04; 12(4):283-292. . View in PubMed. Adult With PHOX2B Mutation and Late-Onset Congenital Central Hypoventilation Syndrome J Clin Sleep Med. 2018 12 15; 14(12):2079-2081. . View in PubMed. A System Analysis of Delay in Outpatient Respiratory Equipment Delivery Care Manag J. 2016 Dec 01; 17(4):161-169. . View in PubMed. Children and Young Adults Who Received Tracheostomies or Were Initiated on Long-Term Ventilation in PICUs Pediatr Crit Care Med. 2016 08; 17(8):e324-34. . View in PubMed. Forensic Sci Med Pathol. 2016 06; 12(2):229-31. . View in PubMed. Benign and Deleterious Cystic Fibrosis Transmembrane Conductance Regulator Mutations Identified by Sequencing in Positive Cystic Fibrosis Newborn Screen Children from California PLoS One. ...
Introduction. Cystic fibrosis (CF) is the most common and lethal autosomal recessive genetic diseases and affects one in 2,500 Caucasians. The risk of its heterozygote in the general population is one to 25. More than 1,000 mutations have been identified to the CFTR gene1, which codes for a protein containing 1,489 amino acids. Cystic Fibrosis is characterized by abnormal chlorine flow at the apical membrane of epithelial cells, causing diverse clinical manifestations including pancreatic insufficiency, lung disease, meconium ileus, elevated sweat chlorine levels and obstruction of the vas deferens. The extreme diversity of CF phenotypes is probably influenced by other genetic areas, distant from the CFTR locus. Many of the genes that are studied nowadays as modifiers of CF, particularly among those that influence the severity of the lung disease, are involved in controlling infection, immunity and inflammation. Some of these include the class II HLA antigens, mannose-binding lectin and alpha 1 ...
Review question We looked for evidence of which antibiotics are best to treat a flare up of symptoms in people with cystic fibrosis with persistent Burkholderia cepacia complex lung infection.. Background Cystic fibrosis is a common inherited condition where the lungs often become blocked with mucus. This harms the lungs defences and often results in chronic, persistent infections that cannot be cleared by antibiotics. People with cystic fibrosis often need courses of antibiotics to reduce their symptoms (for instance cough, excess mucus and breathlessness) when these flare up or worsen. Such episodes are called exacerbations, and are usually treated with intravenous antibiotics (given through a drip into a vein). One group of bacteria that can infect the lungs of people with cystic fibrosis is called the Burkholderia cepacia complex. These closely-related bacteria are found widely in the environment and do not cause infections in healthy people who do not have cystic fibrosis. They are ...
Cystic fibrosis is a multisystem disease that affects the lungs, pancreas, gastrointestinal tract and reproductive systems. Symptoms of cystic fibrosis can vary amongst individuals and most frequently include lower airway inflammation and chronic infections that can progress to end-stage lung disease. Pancreatic insufficiency with malabsorption is a complication that occurs in many individuals with CF. Most males with cystic fibrosis experience infertility. Individuals with cystic fibrosis have normal intelligence and the average median survival is currently 37 years. The most common cause of death is respiratory failure. Treatment of an individual with CF can include medication to improve digestion, monitored nutrition and lung therapy. Up to 15% of individuals with a diagnosis of cystic fibrosis can have a mild form with an average life expectancy of 56 years. Cystic Fibrosis is inherited in an autosomal recessive manner.. Our Tests ...
Nontuberculous mycobacteria are bacteria that are in the same family as tuberculosis and are commonly found in the soil and water. These bacteria can be found in the lungs of people with cystic fibrosis and can cause their lung function to worsen. Although there are guidelines on which antibiotics to use to treat lung infection due to these bacteria, these recommendations are not specific for people with cystic fibrosis. It is also not clear which are the most effective antibiotics. The main purpose of this review was to determine whether treatment with different antibiotic combinations for nontuberculous mycobacterial infection would improve lung function or decrease the frequency of chest infections in people with cystic fibrosis. We found one randomized controlled trial but it included both people with and without cystic fibrosis and we could not get the information specifically about individuals with cystic fibrosis so could not include the information in this review. Until the time when ...
To gain insight into aberrant cytokine regulation in cystic fibrosis (CF), we compared the phenotypic manifestations of allergen challenge in gut-corrected CFTR-deficient mice with background-matched C57Bl6 (B6) mice. Aspergillus fumigatus (Af) antigen was used to mimic allergic bronchopulmonary aspergillosis, a peculiar hyper-IgE syndrome with a high prevalence in CF patients. CFTR-/-, C57BL/6 and FVB/NJ mice were sensitized with Af antigen by serial intraperitoneal injections. Control mice were mock sensitized with PBS. Challenges were performed by inhalation of Af antigen aerosol. After Af antigen challenge, histologic analysis showed goblet cell hyperplasia and lymphocytic infiltration in both strains. However, total serum IgE levels were markedly elevated in CF mice. Sensitized CF mice showed a five-fold greater IgE response to sensitization as compared with B6- and FVB-sensitized controls. Additional littermate controls to fully normalize for B6-FVB admixture in the strain background confirmed the

Macromolecular conjugates of cystic fibrosis transmembrane conductance     regulator protein inhibitors and uses therefor -...Macromolecular conjugates of cystic fibrosis transmembrane conductance regulator protein inhibitors and uses therefor -...

... the ion transport activity of a cystic fibrosis transmembrane conductance regulator (CFTR) and that is linked to a ... Ma et al., "High-affinity Activators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Chloride Conductance ... Macromolecular conjugates of cystic fibrosis transmembrane conductance regulator protein inhibitors and uses therefor ... Macromolecular conjugates of cystic fibrosis transmembrane conductance regulator protein inhibitors and uses therefor ...
more infohttp://www.patentgenius.com/patent/8552067.html

Role of calpain in the regulation of CFTR (cystic fibrosis transmembrane conductance regulator) turnover | Biochemical JournalRole of calpain in the regulation of CFTR (cystic fibrosis transmembrane conductance regulator) turnover | Biochemical Journal

... cystic fibrosis; CFTR, cystic fibrosis transmembrane conductance regulator; CMAC, 7-amino-4-chloromethylcoumarin; ECL, enhanced ... Role of calpain in the regulation of CFTR (cystic fibrosis transmembrane conductance regulator) turnover. Monica Averna, ... The level of the mature native 170 kDa form of CFTR (cystic fibrosis transmembrane conductance regulator) at the plasma ... Role of calpain in the regulation of CFTR (cystic fibrosis transmembrane conductance regulator) turnover ...
more infohttp://www.biochemj.org/content/430/2/255

Cystic fibrosis transmembrane conductance regulator gene | definition of cystic fibrosis transmembrane conductance regulator...Cystic fibrosis transmembrane conductance regulator gene | definition of cystic fibrosis transmembrane conductance regulator...

What is cystic fibrosis transmembrane conductance regulator gene? Meaning of cystic fibrosis transmembrane conductance ... What does cystic fibrosis transmembrane conductance regulator gene mean? ... cystic fibrosis transmembrane conductance regulator gene explanation free. ... Looking for online definition of cystic fibrosis transmembrane conductance regulator gene in the Medical Dictionary? ...
more infohttp://medical-dictionary.thefreedictionary.com/cystic+fibrosis+transmembrane+conductance+regulator+gene

Novel role of cystic fibrosis transmembrane conductance regulator in maintaining adult mouse olfactory neuronal homeostasis  -...Novel role of cystic fibrosis transmembrane conductance regulator in maintaining adult mouse olfactory neuronal homeostasis -...

Novel role of cystic fibrosis transmembrane conductance regulator in maintaining adult mouse olfactory neuronal homeostasis ... The olfactory epithelium (OE) of mice deficient in cystic fibrosis transmembrane conductance regulator (CFTR) exhibits ion ... The olfactory epithelium (OE) of mice deficient in cystic fibrosis transmembrane conductance regulator (CFTR) exhibits ion ... Download PDF Novel role of cystic fibrosis transmembrane conductance regulator in maintaining adult mouse olfactory neuronal ...
more infohttp://www.zora.uzh.ch/id/eprint/105503/

Interactions between Impermeant Blocking Ions in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore:...Interactions between Impermeant Blocking Ions in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore:...

"Interactions between Impermeant Blocking Ions in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore ... Dynamic control of cystic fibrosis transmembrane conductance regulator Cl-/HCO 3 - selectivity by external Cl- ... Novel regulation of cystic fibrosis transmembrane conductance regulator (CFTR) channel gating by external chloride ... Heterologous expression systems for study of cystic fibrosis transmembrane conductance regulator. Chang, X.-B.; Kartner, N.; ...
more infohttps://www.deepdyve.com/lp/springer_journal/interactions-between-impermeant-blocking-ions-in-the-cystic-fibrosis-UMFhN4iRB1

Stable dimeric assembly of the second membrane-spanning domain of CFTR (cystic fibrosis transmembrane conductance regulator)...Stable dimeric assembly of the second membrane-spanning domain of CFTR (cystic fibrosis transmembrane conductance regulator)...

Stable dimeric assembly of the second membrane-spanning domain of CFTR (cystic fibrosis transmembrane conductance regulator) ... Stable dimeric assembly of the second membrane-spanning domain of CFTR (cystic fibrosis transmembrane conductance regulator) ... Stable dimeric assembly of the second membrane-spanning domain of CFTR (cystic fibrosis transmembrane conductance regulator) ... Stable dimeric assembly of the second membrane-spanning domain of CFTR (cystic fibrosis transmembrane conductance regulator) ...
more infohttp://www.biochemj.org/content/375/3/633

Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and...Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and...

Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and ... 246 with nonsense mutations in each CF gene has no detectable cystic fibrosis transmembrane conductance regulator (CFTR) ... Cystic fibrosis (CF) is the most common, lethal inherited disorder in the Caucasian population. We have recently reported two ... W1316X in respiratory epithelial cells of patients with cystic fibrosis Academic Article Overview. MeSH Major * Bronchi ...
more infohttp://vivo.med.cornell.edu/display/pubid0026322140

Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path...Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path...

We developed molecular models for the cystic fibrosis transmembrane conductance regulator chloride channel based on the ... Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path ... Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path ... Animals, Anions, Cystic Fibrosis Transmembrane Conductance Regulator, Humans, Ion Transport, Models, Molecular, Molecular ...
more infohttps://www.neuroscience.ox.ac.uk/publications/322751

Function and Expression of Cystic Fibrosis Transmembrane Conductance Regulator after Small Intestinal Transplantation in Mice -...Function and Expression of Cystic Fibrosis Transmembrane Conductance Regulator after Small Intestinal Transplantation in Mice -...

Function and Expression of Cystic Fibrosis Transmembrane Conductance Regulator after Small Intestinal Transplantation in Mice ... Cystic fibrosis transmembrane conductance regulator CFTR mediates HCO3- and Cl- secretions in intestinal epithelial cells. In ... Function and Expression of Cystic Fibrosis Transmembrane Conductance Regulator after Small Intestinal Transplantation in Mice. ... Function and Expression of Cystic Fibrosis Transmembrane Conductance Regulator after Small Intestinal Transplantation in Mice ...
more infohttp://libros.duhnnae.com/2017/jun8/149823671728-Function-and-Expression-of-Cystic-Fibrosis-Transmembrane-Conductance-Regulator-after-Small-Intestinal-Transplantation-in-Mice.php

Successful targeting of the mouse cystic fibrosis transmembrane conductance regulator gene in embryonal stem cells. - Oxford...Successful targeting of the mouse cystic fibrosis transmembrane conductance regulator gene in embryonal stem cells. - Oxford...

... of the cystic fibrosis transmembrane conductance regulator gene, as the first critical step towards this end. The targeting ... the site of the major mutation in patients with cystic fibrosis. The targeted cells are pluripotent and competent to form ... We wish to construct a mouse model for the human inherited disease cystic fibrosis. We describe here the successful targeting ... Animals, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Disease Models, Animal, Embryo, Mammalian, Exons ...
more infohttps://www.neuroscience.ox.ac.uk/publications/251641

cAMP-Protein Kinase A Activates Cystic Fibrosis Transmembrane Conductance Regulator for ATP Release from Rat Skeletal Muscle...cAMP-Protein Kinase A Activates Cystic Fibrosis Transmembrane Conductance Regulator for ATP Release from Rat Skeletal Muscle...

cAMP-Protein Kinase A Activates Cystic Fibrosis Transmembrane Conductance Regulator for ATP Release from Rat Skeletal Muscle ... We have shown that cystic fibrosis transmembrane conductance regulator CFTR is involved in ATP release from skeletal muscle at ... cAMP-Protein Kinase A Activates Cystic Fibrosis Transmembrane Conductance Regulator for ATP Release from Rat Skeletal Muscle ... cAMP-Protein Kinase A Activates Cystic Fibrosis Transmembrane Conductance Regulator for ATP Release from Rat Skeletal Muscle ...
more infohttp://libros.duhnnae.com/2017/jun7/149818902299-cAMP-Protein-Kinase-A-Activates-Cystic-Fibrosis-Transmembrane-Conductance-Regulator-for-ATP-Release-from-Rat-Skeletal-Muscle-during-Low-pH-or-Contract.php

Cystic fibrosis transmembrane conductance regulator (IPR009147) | InterPro | EMBL-EBICystic fibrosis transmembrane conductance regulator (IPR009147) | InterPro | EMBL-EBI

Cystic fibrosis transmembrane conductance regulator (CFTR, also known as ABCC7) is an eukaryotic protein belonging to the ABC-C ... Dysfunction of the CFTR channel causes the life-threatening disease, cystic fibrosis, in which trans-epithelial ion transport ... and a less conserved transmembrane domain (TMD). Eukaryotic ABC proteins are usually organised either as full transporters ( ... Cystic fibrosis transmembrane conductance regulator (IPR009147). Short name: CFTR/ABCC7 Family relationships None. ...
more infohttp://www.ebi.ac.uk/interpro/entry/IPR009147

Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive.  - PubMed - NCBIProcessing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive. - PubMed - NCBI

Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive.. Denning GM1, Anderson MP, ... Cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane Cl- channel regulated by cyclic AMP-dependent ... The most common mutation in cystic fibrosis is deletion of phenylalanine at residue 508 (CFTR delta F508) (ref. 10). Studies on ... Mutations in CFTR cause cystic fibrosis partly through loss of cAMP-regulated Cl- permeability from the plasma membrane of ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/1380673?dopt=Abstract

JCI -
Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammationJCI - Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammation

The cystic fibrosis transmembrane conductance regulator (CFTR) is mutated in CF, and we hypothesized that dysfunctional CFTR in ... Cystic fibrosis (CF) lung disease is characterized by an inflammatory response that can lead to terminal respiratory failure. ... Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammation. Guadalupe Ortiz- ... Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammation. *Text ...
more infohttps://www.jci.org/articles/view/129635/pdf

Macromolecular complexes of cystic fibrosis transmembrane conductance regulator and its interacting partners.  - PubMed - NCBIMacromolecular complexes of cystic fibrosis transmembrane conductance regulator and its interacting partners. - PubMed - NCBI

Cystic Fibrosis Transmembrane Conductance Regulator/genetics. *Cystic Fibrosis Transmembrane Conductance Regulator/metabolism* ... The cystic fibrosis transmembrane conductance regulator (CFTR) is the product of the gene mutated in patients with cystic ... Macromolecular complexes of cystic fibrosis transmembrane conductance regulator and its interacting partners.. Li C1, Naren AP. ... Cystic Fibrosis/physiopathology. *Cystic Fibrosis Transmembrane Conductance Regulator/chemistry. * ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/15936089?dopt=Abstract

Cystic fibrosis transmembrane conductance regulator - WikipediaCystic fibrosis transmembrane conductance regulator - Wikipedia

"Cystic fibrosis transmembrane conductance regulator and the etiology and pathogenesis of cystic fibrosis". FASEB J. 6 (10): ... The Cystic Fibrosis Transmembrane Conductance Regulator Protein The Human Gene Mutation Database - CFTR Records Cystic Fibrosis ... "Relationships between cystic fibrosis transmembrane conductance regulator, extracellular nucleotides and cystic fibrosis". ... Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and chloride channel in vertebrates that is ...
more infohttps://en.wikipedia.org/wiki/Cystic_fibrosis_transmembrane_conductance_regulator

The Cystic Fibrosis Transmembrane Conductance Regulator by Kevin L. Kirk, David C. Dawson | WaterstonesThe Cystic Fibrosis Transmembrane Conductance Regulator by Kevin L. Kirk, David C. Dawson | Waterstones

Buy The Cystic Fibrosis Transmembrane Conductance Regulator by Kevin L. Kirk, David C. Dawson from Waterstones today! Click and ... The Cystic Fibrosis Transmembrane Conductance Regulator - Molecular Biology Intelligence Unit (Hardback). Kevin L. Kirk (editor ... The Cystic Fibrosis Transmembrane Conductance Regulator addresses a select series of `hot topics that relate to the function ... Given the general interest in CFTR, this collection will appeal to a broad readership with interests in CFTR, cystic fibrosis, ...
more infohttps://www.waterstones.com/book/cystic-fibrosis-transmembrane-conductance-regulator/kevin-l-kirk/david-c-dawson/9780306478376

A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype | American Academy of PediatricsA Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype | American Academy of Pediatrics

A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype. Eitan Kerem, Malka Nissim- ... A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype. Eitan Kerem, Malka Nissim- ... A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype Message Subject (Your Name) has ... A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype. Eitan Kerem, Malka Nissim- ...
more infohttps://pediatrics.aappublications.org/content/100/3/e5/tab-e-letters

Article Metrics] Cystic  fibrosis transmembrane conductance regulator modulators in cys | CPAAArticle Metrics] Cystic fibrosis transmembrane conductance regulator modulators in cys | CPAA

Mutations of the CFTR gene cause cystic fibrosis (CF), the most common recessive monogenic disease worldwide. These mutations ... Cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis: current perspectives Béla Z Schmidt,1 Jérémy ... Cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis: current perspectives. *Abstract ...
more infohttps://www.dovepress.com/article_metric.php?article_id=29031

Graph-Theoretic Models of Mutations in the Nucleotide Binding Domain 1 of the Cystic Fibrosis Transmembrane Conductance...Graph-Theoretic Models of Mutations in the Nucleotide Binding Domain 1 of the Cystic Fibrosis Transmembrane Conductance...

X. Wang, J. Matteson, Y. An et al., "COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER ... "Impact of the ΔF508 mutation in first nucleotide-binding domain of human cystic fibrosis transmembrane conductance regulator on ... "Multiple membrane-cytoplasmic domain contacts in the cystic fibrosis transmembrane conductance regulator (CFTR) mediate ... Models of Mutations in the Nucleotide Binding Domain 1 of the Cystic Fibrosis Transmembrane Conductance Regulator. Debra J. ...
more infohttps://www.hindawi.com/journals/cbj/2013/938169/ref/

JCI -
Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ...JCI - Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ...

Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ ... Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ ... We have used in situ hybridization to localize expression of the cystic fibrosis transmembrane conductance regulator (CFTR) ...
more infohttps://www.jci.org/articles/view/116966/scanned-page/354

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) GeneCystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene was identified in 1989 by geneticist Lap-Chee Tsui and his ... Winikates, Kristina, "Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene". Embryo Project Encyclopedia (2012-01-01 ... Cystic fibrosis is an autosomal recessive disease, meaning it is inherited when a child receives one mutated copy of the CFTR ... Cystic Fibrosis in the 21st Century. Basel, Switzerland: S. Karger AG, 2006. ...
more infohttps://embryo.asu.edu/pages/cystic-fibrosis-transmembrane-conductance-regulator-cftr-gene

The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi...The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi...

The most common cause of cystic fibrosis is deletion of Phe-508 (delta F508) from the cystic fibrosis transmembrane conductance ... The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi ... The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi ... The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi ...
more infohttps://www.pnas.org/content/90/20/9480?ijkey=342d87e056a8da82d9990cac2e37c2a2146219fa&keytype2=tf_ipsecsha

Aspirin and Some Other Nonsteroidal Anti-Inflammatory Drugs Inhibit Cystic Fibrosis Transmembrane Conductance Regulator Protein...Aspirin and Some Other Nonsteroidal Anti-Inflammatory Drugs Inhibit Cystic Fibrosis Transmembrane Conductance Regulator Protein...

Cystic fibrosis (CF) is caused by mutations in the CF gene, which encodes CF transmembrane conductance regulator protein (CFTR ... Aspirin and Some Other Nonsteroidal Anti-Inflammatory Drugs Inhibit Cystic Fibrosis Transmembrane Conductance Regulator Protein ... a transmembrane protein that acts as a cAMP-regulated chloride channel. The disease is characterized by inflammation but the ...
more infohttps://www.hindawi.com/journals/mi/1999/175898/abs/

Structure Cluster 









- 1CKY: CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR: SOLUTION STRUCTURES OF PEPTIDES BASED...Structure Cluster - 1CKY: CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR: SOLUTION STRUCTURES OF PEPTIDES BASED...

Cystic fibrosis transmembrane conductance regulator: solution structures of peptides based on the Phe508 region, the most ... Description: PROTEIN (CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR)) protein , Length: 26 No structure alignment ... CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR: SOLUTION STRUCTURES OF PEPTIDES BASED ON THE PHE508 REGION, THE MOST ...
more infohttp://www.rcsb.org/pdb/explore/structureCluster.do?structureId=1CKY
  • Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path and locates a "bottleneck" in the pore. (ox.ac.uk)
  • A high fat calorie diet is advocated for patients with cystic fibrosis (CF) however the lipid profiles of individuals with CF, including those with CF-related diabetes (CFRD), are not well studied. (diff.org)
  • Macromolecular complexes of cystic fibrosis transmembrane conductance regulator and its interacting partners. (nih.gov)
  • These results reconcile previous contradictory observations and suggest that the mutant most commonly associated with cystic fibrosis is temperature-sensitive. (nih.gov)
  • With these results, we propose that K18 as a new therapeutic target and curcumin, and/or its analogs, might be considered as potential therapeutic agents for cystic fibrosis. (aspetjournals.org)
  • COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER uses di-acidic exit code," Journal of Cell Biology , vol. 167, no. 1, pp. 65-74, 2004. (hindawi.com)
  • article{Picciano2003Rme1RT, title={Rme-1 regulates the recycling of the cystic fibrosis transmembrane conductance regulator. (semanticscholar.org)
  • Decreased total serum coenzyme-Q10 concentrations: a longitudinal study in children with cystic fibrosis. (diff.org)