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

The microanatomy of mucin granule release from epithelial goblet cells has been investigated in guinea pig tracheae. Using a tannic acid arrest procedure, granule release under basal conditions and after high K+ or acetylcholine (ACh) application was arrested and a variety of granule fusion sites were identified in ultrathin sections and freeze-fracture replicas. Rather than there being subclasses of secretory cells containing either electron-lucent granules (indicative of mucin) or smaller electron-dense (serous) granules, the majority of secretory cells in both control and treated groups contained granules with an electrondense core surrounded by an electron-lucent region. Granule release sites were of three principal types: (1) simple exocytosis, where the membranes of single granules fused directly with the plasma membrane to give an "omega" profile; (2) compound exocytosis, where granule membranes, fused together intracellularly, were found in continuity with the plasma membrane; and (3) apocrine-like secretion, which involved the loss of the central apical mass of granules together with elements of the cell cytoplasm. In treated preparations, there was an increase in the number of cells exhibiting fusion sites; the percentage showing simple fusions fell from 82% to 59% (with ACh) and 57% (with KCl), whereas the percentage of cells exhibiting compound and apocrine-like secretion increased. Dense cores were frequently retained at the sites of fusion and, despite the expansive decondensation of mucin known to occur, there was also evidence of some retention of the electron-lucent material.
Am J Respir Cell Mol Biol 1996 Oct
PMID:Microanatomy of secretory granule release from guinea pig tracheal goblet cells. 887 87

Endogenous aspiration of nasooropharyngeal secretions is a major source of Pseudomonas aeruginosa to lungs. To understand the mechanism of binding between P. aeruginosa and nasooropharyngeal secretions, we have utilized an overlay binding assay employing P. aeruginosa nonpilus protein adhesins (18 kDa and 15 kDa) and mucins from human saliva, tracheobronchial and nasopharyngeal secretions. Nasopharyngeal mucin bound to both the 18 kDa and 15 kDa adhesins. A high molecular weight salivary mucin and tracheobronchial mucin bound only to the 18 kDa adhesin. On the other hand, asialonasopharyngeal and asialotracheobronchial mucins did not bind to either of the adhesins. Binding of nasopharyngeal mucin to the 18 kDa and 15 kDa was not inhibitable by glycoproteins, bovine submaxillary mucins and sialic acid. Further, a low molecular weight salivary mucin which contains sialylated oligosaccharides also did not bind to either of the adhesins. Collectively, the results suggest that binding between P. aeruginosa and mucins may involve specific receptors and adhesins.
Biochem Mol Biol Int 1996 Oct
PMID:Binding between Pseudomonas aeruginosa adhesins and human salivary, tracheobronchial and nasopharyngeal mucins. 889 63

Extracellular nucleotides stimulate mucin release by binding to the P2u receptor coupled to phospholipase C via G proteins (Br. J. Pharmacol. 103:1053-1056, 1991; Am. J. Respir. Cell Mol. Biol. 8:121-125, 1993). In the present study, we intended to investigate pathways downstream to the phospholipase C activation which is responsible for adenosine triphosphate (ATP)-induced mucin release in hamster tracheal epithelial cells in primary culture. We have found that: (1) Ca2+ ionophores (A23187 and ionomycin) did not affect mucin release even at 1 microM; (2) thapsigargin (10 microM), either alone or in combination with ATP (20 microM), did not enhance mucin release over its respective control group; (3) pretreatment of hamster tracheal surface epithelial (HTSE) cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM) (50 microM) did not inhibit ATP-induced mucin release; (4) 4beta-phorbol 12alpha-myristate 13-acetate (PMA, 1 microM) stimulated mucin release and its effect was completely blocked by protein kinase C inhibitors such as sphingosine (10 microM) and calphostin C (0.1 microM), whereas ATP-induced mucin release was blocked, only in part, by these inhibitors; (5) desensitization of protein kinase C by pretreatment with PMA inhibited the PMA-induced mucin release completely, however, ATP-induced mucin release was inhibited only partially. We conclude that mucin release by ATP does not require an increase in the intracellular Ca2+ level but involves the activation of protein kinase C. The results also suggest the presence of another mechanism separate from the phospholipase C-protein kinase C pathway for the ATP-induced mucin release.
Am J Respir Cell Mol Biol 1997 Feb
PMID:ATP-induced mucin release from cultured airway goblet cells involves, in part, activation of protein kinase C. 903 27

The equine embryonic capsule, an acellular covering that envelops the conceptus during the second and third weeks of pregnancy, is composed of mucin-like glycoproteins. Its structure is consistent with a dual role during early pregnancy: protection of the conceptus, and communication between the embryo and the mother. Loss of sialic acid from the capsular glycoproteins at day 16 correlates with the time of "fixation," or loss of conceptus mobility throughout the uterine horns. This study investigated how the structure of the capsule is linked to the maintenance of pregnancy. Six pregnancies, confirmed by ultrasound, were terminated by prostaglandin injection on day 14, prior to the time of embryo fixation. These "defective" conceptuses were collected at day 17, and the structure and molecular properties of their capsules were compared to those of day 17 conceptuses collected from 5 normal pregnancies. Defective capsules were not significantly different from normal capsules in terms of dry weight, amino acid composition, and content of neutral and amino sugars. However, defective capsules failed to show the loss of sialic acid normally occurring around the time of embryo fixation. Analysis of the capsular mucins following trypsin digestion was carried out by radioactive labeling with 3H on sialyl-oligosaccharides and 125I on tyrosine residues, followed by fast protein liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Differences in the trypsin fragmentation patterns indicated increased susceptibility of the defective capsules to proteolysis. We conclude that there is a temporal association between desialylation of the equine capsule and embryonic survival, and that failure to desialylate alters the properties of the capsule.
Mol Reprod Dev 1997 Mar
PMID:Biochemical changes in the equine capsule following prostaglandin-induced pregnancy failure. 904 Nov 31

The 35/50 kDa mucin-like surface glycoprotein (gp35/50) of Trypanosoma cruzi metacyclic trypomastigotes has been implicated in mammalian cell invasion. In this study we investigated whether the sialyl residues of gp35/50 are required for interaction of parasites with target cells. After treatment with bacterial neuraminidase, the metacyclic forms (G strain) remained reactive with the monoclonal antibody (mAb) 10D8 but lost their reactivity with mAb 3C9, that recognizes sialic acid-containing epitopes on gp35/50, and entered HeLa cells in significantly higher numbers as compared to untreated controls. Resialylation of gp35/50, by incubation of parasites with T. cruzi trans-sialidase and sialyl lactose, restored the reactivity with mAb 3C9 as well as the affinity for sialic acid specific lectin. Accordingly, the rate of invasion of resialylated parasites was reduced to levels similar to those observed before desialylation. Purified G strain gp35/50, desialylated by neuraminidase treatment, bound to HeLa cells more than its sialylated counterpart. The Ca2+ signaling activity, which has been associated with cell invasion, was also determined by measuring the cytosolic Ca2+ concentration ([Ca2+]i), in HeLa cells upon interaction with sonicated extracts from untreated or neuraminidase-treated parasites, or with purified gp35/50 in its sialylated or desialylated form. Consistent with the results of cell invasion assay, the desialylated parasite preparations, as well as the sialic acid free gp35/50, induced an average elevation in [Ca2+]i significantly higher than that triggered by untreated controls. None of these effects, namely the increase in infectivity and Ca2+ signaling activity, was observed with neuraminidase-treated CL strain metacyclic trypomastigotes, which express a variant form of sialic acid gp35/50 molecule that is not recognized by mAb 10D8 and apparently is not involved in target cell invasion.
Mol Biochem Parasitol 1997 Jan
PMID:Removal of sialic acid from mucin-like surface molecules of Trypanosoma cruzi metacyclic trypomastigotes enhances parasite-host cell interaction. 904 21

A partial cDNA (pAM1) encoding a major airway mucin glycoprotein with novel tandem repetitive sequence has recently been cloned (Shankar, V., M. S. Gilmore, R. C. Elkins, and G. P. Sachdev. 1994. Biochem. J. 300:295-298). In this article, we report additional new sequence derived by 3'-rapid amplification of cDNA ends technique. The sequence corresponds to a stop codon, 3'-untranslated region of 458 bp, a polyadenylation signal, and poly A+ tail, and represents the extreme carboxy terminus of MUC8. A plasmid construct (pAM3) in pBluescript was generated by in-frame ligation of pAM1 to the 479-bp 3'UTR of MUC8. A 5'-end 325-bp fragment of this cDNA subcloned into the protein fusion and expression vector pET28b(+) was used to generate fusion protein under the control of T7 promoter. The purified fusion protein as well as synthetic peptide corresponding to the MUC8 repeat sequence (TSCPRPLQEGTPGS) were used to raise polyclonal antibodies in rabbits. The antiserum to the fusion protein and to the synthetic peptide reacted with the deglycosylated major tracheobronchial mucin. Immunohistochemical studies using the above antibodies localized the MUC8 protein product to submucosal glands in human tracheal epithelium. Furthermore, the gene from which this cDNA is derived, was mapped to chromosome 12 using DNA from a panel of human-mouse somatic cell hybrids. Fluorescence in situ hybridization was used to assign the regional localization to 12q24.3. Since the eight known human mucin genes map to other chromosomes, we have named this gene MUC8, in accordance with mucin gene nomenclature.
Am J Respir Cell Mol Biol 1997 Mar
PMID:Chromosomal localization of a human mucin gene (MUC8) and cloning of the cDNA corresponding to the carboxy terminus. 907 Jun 7

Mucus hypersecretion and plugging of lower respiratory tract airways contributes to the morbidity and mortality associated with asthma. Interleukin (IL)-4 plays a putative role in some forms of asthma. Thus, transgenic mice that overexpress murine IL-4 selectively within the lung were used to study the effect of IL-4 on mucus glycoprotein gene expression and mucin release. Histologic examination of lung sections from IL-4 mice revealed that nonciliated epithelial cells from conducting airways were hypertrophic, due at least in part to the accumulation of mucus glycoprotein. The cytoplasm of these cells stained positively for glycoproteins using mucicarmine, alcian blue (AB), and periodic acid-Schiff (PAS). Ciliated cells were also enlarged but did not show any mucin-specific staining. Inclusion granules typically found in nonciliated (Clara) cells of control mice were absent in the IL-4 transgenic mice. Northern blot analysis of total RNA from lung tissue revealed that the expression of the MUC5AC, but not MUC2, mucin gene was distinctly upgraded in IL-4 transgenic mice compared to transgene-negative controls. In addition, a 5- to 10-fold increase in AB- and PAS-positive material was found in lavage fluid from IL-4 overexpressing mice compared to transgene-negative controls. Thus, the overexpression of IL-4 locally within the lung enhances mucus glycoprotein synthesis by altering gene expression, results in the accumulation of mucus glycoprotein in nonciliated epithelial cells, and induces the release of mucus into the airway lumen. We therefore hypothesize that the overproduction of mucus seen in some patients with asthma may be a direct result of the action of IL-4 within the inflamed lung.
Am J Respir Cell Mol Biol 1997 Apr
PMID:A novel role for murine IL-4 in vivo: induction of MUC5AC gene expression and mucin hypersecretion. 911 59

We improved the enzyme-linked lectin-binding assay (ELLA) to determine the differences in the carbohydrate chains of corpus, antral, duodenal ant colonic rat mucins. First we have improved the optimal conditions of this assay for mucins; ELLA makes possible the detection of 1.5 ng of hexose in rat gastrointestinal mucins (5-7 ng of mucins). Salt concentrations of several dozens mM are required for mucin coating on the plate. Non-ionic detergents diminish the adsorption of mucins onto the plate. Secondly we tested a set of 8 lectins to compare their binding to the gastrointestinal mucin samples. It is possible to detect crude mucins as well as purified mucins using ELLA. Gastric mucins have less Tn-antigen than duodenal and colonic mucins. Corpus and duodenal mucins have more of the H-type 2 chain than antral and colonic mucins.
Comp Biochem Physiol B Biochem Mol Biol 1997 Feb
PMID:Comparative study of carbohydrate portion of gastrointestinal mucins using enzyme-linked lectin-binding assay (ELLA). 915 80

The purpose of our studies was to identify factors which regulate the composition of airway secretions produced by normal human tracheobronchial epithelial (NHTBE) cells. Individual factors were removed from the culture media of NHTBE cells grown in air-liquid interface (ALI) cultures (which support mucociliary differentiation) and the effects on mucin, lysozyme (LZ), and secretory leukocyte protease inhibitor (SLPI) secretion and gene expression were examined. Deletion of hydrocortisone, epinephrine, transferrin, or gentamycin-amphotericin from the media had no reproducible effects; deletion of insulin was incompatible with culture growth. We identified 3 factors, namely retinoic acid (RA), triiodothyronine (T3) and collagen gel substratum, which had a major impact on the profile of NHTBE secretions. Removal of RA from the media caused a drastic decrease in mucin secretion and a decrease in expression of the mucin genes MUC2 and MUC5AC.LZ and SLPI secretions were increased in these cultures. Paradoxically LZ mRNA was decreased, while SLPI mRNA levels were increased. Removal of T3 selectively increased mucin secretion, MUC2 gene expression was not affected, but MUC5AC mRNA levels reproducibly increased, suggesting that the expression of these two mucin genes is differentially regulated. LZ and SLPI secretion levels were not significantly affected by deletion of T3 from the culture media; however, LZ mRNA levels were increased in the absence of T3 while SLPI transcript levels were not affected. Omission of the attachment substratum, type I collagen gel, resulted in significant increases in all 3 secretory products. MUC2 and MUC5AC steady state mRNA levels were not consistently affected. In contrast LZ and SLPI gene expression were reproducibly increased. Our studies show that individual factors in the epithelial environment can regulate expression of specific secretory cell gene products in a highly selective manner.
Am J Respir Cell Mol Biol 1997 Jun
PMID:Regulation of the secretory phenotype of human airway epithelium by retinoic acid, triiodothyronine, and extracellular matrix. 919 74

A sialic acid-binding lectin that agglutinates a variety of erythrocytes and bacteria and react with sialoconjugates and purified lipopolysaccharides from marine vibrios has been affinity purified from hemolymph of the horse mussel Modiolus modiolus using Bovine submaxillary mucin conjugated to CNBr-activated Sepharose 4B. The lectin demonstrated heterogeneous activity, and at least two main entities were partially characterized, and are referred to as modiolin H and modiolin E activities for the agglutination of human and horse (equine) erythrocytes, respectively. Only modiolin E activity required calcium ions for hemagglutination. The M. modiolus lectin was mainly specific for NeuAc, although the lectin demonstrated a broader range of specificity, similarly to the Limulus polyphemus lectin. The purified lectin was a glycoprotein, and in the native state existed as aggregates with M(r) in the range of 100-1,300 kDa as observed by gradient-gel electrophoresis and gel filtration on Biogel and Superose. SDS-PAGE under reducing conditions revealed three subunits of M(r) 14, 17.5 and 20 kDa. Various marine bacteria adsorbed the hemagglutinating activities of the M. modiolus lectin. Purified LPS preparations from various pathogenic marine vibrios were also effective inhibitors, in particular for modiolin E activity. These results indicate that the lectin play a role in recognition of bacteria.
Comp Biochem Physiol B Biochem Mol Biol 1997 Jun
PMID:A heterogeneous sialic acid-binding lectin with affinity for bacterial LPS from horse mussel (Modiolus modiolus) hemolymph. 922 86


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