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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary cultures of guinea pig tracheal epithelial cells maintained in an air/liquid interface system that maintains differentiated characteristics were grown to near confluence and exposed for 1 h to platelet-activating factor (PAF) on both apical and basal sides. PAF provoked release of high-molecular-weight mucin-like glycoproteins (MLG) from the cells, with maximal stimulation occurring at 10(-8) and 10(-9) M. The inactive form of PAF, lyso-PAF, was without effect. Indomethacin, the cyclooxygenase inhibitor, did not affect secretion stimulated by PAF, but nordihydroguiaretic acid (NDGA), a mixed cyclooxygenase and lipoxygenase inhibitor, attenuated secretion stimulated by PAF in a concentration-dependent manner. High performance liquid chromatography assay of the culture medium after addition of PAF revealed increased production of 15-, 12-, and 5-hydroxyeicosatetraenoic acids (15-, 12-, and 5-HETEs). The stimulatory effect of PAF on both mucin secretion and formation of HETEs was inhibited by the PAF receptor antagonists, CV-3988 and Ro 19 3704, with Ro 19 3704 acting at a concentration 10-fold lower than CV-3988 in inhibiting both effects. When added exogenously to the cell cultures, the combination of 5-, 12-, and 15-HETEs stimulated MLG release in a concentration-dependent manner. The results suggest that PAF stimulates release of MLG by guinea pig airway epithelium in vitro by a mechanism involving binding of PAF to receptors on epithelial cell surfaces, stimulation of lipoxygenase metabolism of arachidonic acid to HETEs within the epithelium, and stimulation of secretion by these epithelial-derived HETEs via an autocrine or paracrine mechanism.
Am J Respir Cell Mol Biol 1992 May
PMID:Platelet-activating factor provokes release of mucin-like glycoproteins from guinea pig respiratory epithelial cells via a lipoxygenase-dependent mechanism. 131 34

From a liver metastasis of a human pancreatic adenocarcinoma, we have established cell lines for studying the cell biology of this tumor. We obtained two cell lines with different morphological, chromosomal and functional properties. One of them, named PaTu 8988s, revealed a solid growth in nude mouse xenografts with cells exhibiting only occasional polar organisation of the cytoplasm. In general, no apical or basolateral plasma membrane domains could be distinguished and the sparse organelles were randomly distributed throughout the cytoplasm. Secretory products, such as mucin, were weakly stained histochemically or were completely absent. Transglutaminase (TGase) activity used as a marker for cellular differentiation was low in these cells. The other cell line, named PaTu 8988t, grew tumors composed of tubular structures when injected subcutaneously into nude mice. Cells were polarized with distinct apical and basolateral plasma membranes and the cytoplasmatic organelles were arranged with the nucleus in the lower part of the cell, while the apical cytoplasm contained the Golgi complex and numerous secretion granules. A high content of mucin was stained histochemically and transglutaminase activity was ten times higher than in PaTu 8988s. Comparing the chromosome number per metaphase plate, both cell lines showed a major peak, with 45-55 chromosomes per metaphase plate in PaTu 8988s and about 110-120 chromosomes per metaphase plate in PaTu 8988t. When the two cell lines were injected intravenously into the tail vein of nude mice, only PaTu 8988s developed metastases localized exclusively in the lung, whereas PaTu 8988t produced no metastases in any organ. We conclude, that two cell lines exhibiting different grades of differentiation as well as a different potency to metastasize can be established from the same primary tumor, and that these cell lines represent a suitable model for further study of the cell biology of human pancreatic adenocarcinoma.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Establishment and characterisation of two cell lines with different grade of differentiation derived from one primary human pancreatic adenocarcinoma. 134 91

In colonic neoplasms, endocrine differentiation is encountered not only in carcinoid tumors but also in adenocarcinomas, where endocrine cells may represent a distinct line of differentiation in the tumor. The significance of endocrine differentiation in colorectal cancer is not well established, partly because of the paucity of tumor cell lines which can serve as a model for studying endocrine differentiation. In this report we describe the properties of NCI-H716 cells, a cell line derived from a poorly differentiated adenocarcinoma of the caecum, under various in vitro conditions and as xenografts in athymic mice. Phenotypical properties were immunohistochemically assessed using a panel of differentiation related antibodies, and also by Northern blot analysis and by electron microscopy. Receptors for biogenic amines and peptide hormones were analyzed by ligand binding assay. These studies show that: 1. NCI-H716 cells can be undifferentiated, or show endocrine, mucin-producing or "amphicrine" properties. 2. Endocrine differentiation of NCI-H716 cells preferentially occurs in xenografts in athymic mice, which suggests that mesenchymal elements induce endocrine differentiation. 3. NCI-H716 cells express large amounts of high affinity receptors for gastrin, serotonin and somatostatin and these substances can regulate growth. Thus, NCI-H716 cells form a suitable model for the study of endocrine differentiation in intestinal epithelium and of auto- or paracrine growth regulation in intestinal neoplasia.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:NCI-H716 cells as a model for endocrine differentiation in colorectal cancer. 135 4

Mucins are the structural components of the mucus gels that protect the respiratory, gastrointestinal, and reproductive tracts. These polydisperse glycoproteins (250,000 to 20,000,000 D) are approximately 80% carbohydrate on a mass basis and have a high intrinsic viscosity due to their large size and extreme hydrophilicity. Mucin oligosaccharides, the structures responsible for this hydrophilicity, are heterogeneous in size and structure but are chiefly O-linked, i.e., they initiate from N-acetylgalactosamine residues attached to threonine and serine residues of the polypeptide backbone. Our understanding of the structure of mucins has advanced rapidly in the last few years with the isolation and sequencing of cDNA clones that encode mucin polypeptide backbones. All currently well-characterized mucins have been found to contain extended arrays of tandemly repeated peptides rich in potential O-glycosylation sites. Less is known about the unique sequences that flank the tandem repeat arrays of secretory mucins, but currently available information indicates that these flanking regions contain cysteine-rich stretches that participate in mucin oligomer formation. Thus, secretory mucins appear to consist of oligomers containing heavily glycosylated domains flanked by unique sequences required for polymerization. Progress has also been made in characterizing the genes that encode mucins. At least four human mucin genes are known at present, although many others may remain to be discovered. Moreover, much work remains before we gain an understanding of the mechanisms involved in the expression of mucin genes and their tissue-specific regulation.
Am J Respir Cell Mol Biol 1992 Dec
PMID:Mucin genes and the proteins they encode: structure, diversity, and regulation. 144 3

To study the proteins and glycoconjugates synthesized by serous cells from human tracheal glands (HTG), isolated HTG cells were cultured in the presence of radiolabeled precursors 14C-proline, Na2(35)SO4, and 3H-fucose. The secretory 14C/35S/3H-radiolabeled proteins and glycoproteins, de novo synthesized by HTG cells, were analyzed by gel filtration chromatography. We observed the incorporation of 14C-proline into antileukoprotease and an unknown 30 kD protein, and the incorporation of 35SO4-- and 3H-fucose into high molecular weight glycoconjugates and sulfoconjugates (M(r) > 1,000,000) and into components with apparent M(r) of approximately 250 and 100 kD. After specific chemical and enzymatic treatment, the 35S- and 3H-glycoconjugates were shown to be -O-linked mucin-like glycoproteins and proteoglycans. These results show that cultured HTG cells synthesize some of the macromolecules identified in bronchial secretions.
Am J Respir Cell Mol Biol 1992 Dec
PMID:Secretory proteins and glycoconjugates synthesized by human tracheal gland cells in culture. 144 7

Human respiratory mucin glycoproteins from patients with cystic fibrosis were purified and oligosaccharide chains were released by treatment with alkaline borohydride. A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. The structures of the purified oligosaccharides were determined by methylation analysis, sequential glycosidase digestion and 'H-NMR spectroscopy. The amount of each chain was determined by compositional analysis. A wide array of discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues were found. Many of the oligosaccharides are related and appear to be precursors of larger chains. The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. Increasing numbers of the repeating sequence shown in the oligosaccharide below is present in the higher molecular weight chains. [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. These chains accumulate and are found in the highest concentrations in these respiratory mucins.
Mol Cell Biochem 1992 Dec 02
PMID:Quantitation and structures of oligosaccharide chains in human trachea mucin glycoproteins. 148 58

Four human lung adenocarcinoma cell lines were established in serum-free F12 medium supplemented with insulin, transferrin, hydrocortisone, cholera toxin, selenium, epidermal growth factor, bovine hypothalamic extract, and retinoic acid. Histochemical analyses with periodic acid-Schiff with and without diastase treatment (PAS-D technique) and immunocytochemistry with a mucin-specific monoclonal antibody demonstrated that three of the cell lines (CL2, CL3, and NCL2) were capable of mucin production. Biochemical characterizations of mucin produced by adenocarcinoma cells were focused on one of the cell lines, CL2 cells, which showed the most prominent reactivity with mucin-specific monoclonal antibody. Biochemical analysis using the mucin precursors [3H]glucosamine and [14C]serine indicated that CL2 cells can synthesize high-molecular-weight (M(r) greater than 200 kD) glycoprotein molecules that can be immunoprecipitated by this mucin-specific monoclonal antibody. The high-molecular-weight glycoproteins isolated from CL2 cells specifically reacted with mucin-specific monoclonal antibody by Western blot analysis, and composition analyses showed high levels of serine and threonine and a low level of aromatic amino acids, which are similar to human airway mucin. These observations suggest that lung adenocarcinoma CL2 cells cultured in this serum-free medium can retain function of airway mucin synthesis. Cell kinetic studies of these four cell lines showed that the cell line (CL1) without the mucin differentiation had a higher proliferative index and a shorter population doubling time as compared with the other three cell lines (CL2, CL3, and NCL2) with mucin differentiation. Examination of the retinoblastoma protein expressions in these adenocarcinoma cell lines revealed a phosphorylated pattern that correlated inversely with the mucin synthesis status of these cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Aug
PMID:Characterization of the mucin differentiation in human lung adenocarcinoma cell lines. 149 5

A membrane-bound sialidase (EC 3.2.1.18) was found in procyclic trypomastigotes of Trypanosoma brucei. The mammalian stage bloodstream form, however, displayed no sialidase activity. This sialidase is an integral surface protein, linked to the membrane via a glycosylphosphatidylinositol anchor. After osmotic lysis and solubilization with Triton CF-54, the enzyme was purified 1900-fold by gel filtration and ion exchange chromatography. Its size, as determined by conventional and high-performance liquid gel chromatography, is 67 kDa. The sialidase is active over a broad pH and temperature range with optima at pH 6.9 and 35 degrees C, respectively. No loss of activity is observed after 4 freeze-thaw cycles. T. brucei sialidase activity is inhibited by N-(4-nitrophenyl)oxamic acid and 2-deoxy-2,3-didehydro-N-acetylneuraminic acid, the latter, however, being less effective. N-Acetylneuraminic acid shows no inhibitory effect, whereas a variety of metal ions are potent inhibitors. The sialidase is activated by di- and tricarboxylic acids, but inhibited by chloride. Relative hydrolysis rates of various sialic acid-containing compounds reveal that de-O-acetylated bovine submandibular gland mucin is the preferred substrate and that alpha(2-3)-linkages are hydrolyzed faster than alpha(2-6)-linkages.
Mol Biochem Parasitol 1992 Aug
PMID:Purification and characterization of a novel sialidase found in procyclic culture forms of Trypanosoma brucei. 151 30

Mucus production is an integral component of airway mucosal inflammation. Platelet-activating factor (PAF) is a phospholipid mediator implicated in the pathogenesis of many inflammatory processes, including airway inflammation. PAF functions as a mucus secretagogue when mucus is quantitated as radiolabeled glycoconjugates released from airway organ cultures. To more directly assess the interaction of PAF and airway epithelial mucous cell secretion, we used primary feline tracheal epithelial cell cultures and an immunoassay for a specific mucous cell secretory vesicle component. Cultured tracheal epithelial cells were shown to synthesize and secrete glycoconjugates with mucin characteristics. These mucin-type glycoconjugates were immunoreactive with a mucous cell-specific antibody. Localization of this antibody to components of the secretory vesicles of cultured epithelial cells was confirmed by electron microscopic immunogold labeling. Using this monoclonal antibody, an immunoassay was developed to quantitate release of immunoreactive material into cell culture media. Exposure of cultures to PAF produced a concentration-dependent, prompt release of immunoreactive material. Concentration-dependent inhibition of this effect was demonstrated by coincubation with the PAF receptor antagonists, WEB 2086 and Ro 19-3704. A component of the signal transduction pathway for PAF effects was studied in cultured tracheal epithelial cells by coincubation of PAF with nordihydroguaiaretic acid (NDGA), a combined lipoxygenase and cyclooxygenase inhibitor, or p-bromophenacyl bromide (BPB), an inhibitor of cellular arachidonic acid release. Both NDGA and BPB blocked PAF-stimulated mucin release in a concentration-dependent manner. These studies demonstrate a direct airway epithelial mucous cell secretagogue effect that appears to be dependent upon airway epithelial PAF receptors and altered cellular lipid metabolism. These findings suggest a direct and potent mechanism for goblet cell secretion during airway inflammation.
Am J Respir Cell Mol Biol 1992 Feb
PMID:Airway epithelial cell mucin release: immunologic quantitation and response to platelet-activating factor. 154 Mar 79

The MUC1 mucin mRNA, for which the cDNA was previously cloned from human breast and pancreatic tissues, was found to be expressed in nasal and bronchial epithelial cell primary cultures from cystic fibrotic, atopic, and normal individuals. Sequence analysis of cDNA clones from the CF/T43 cystic fibrosis nasal epithelial cell line revealed only insignificant differences in the 3' untranslated region of the mRNA when compared with the pancreas and breast mucin cDNAs.
Am J Respir Cell Mol Biol 1992 May
PMID:MUC1 mucin mRNA expression in cultured human nasal and bronchial epithelial cells. 158 Oct 75


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