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Nagoya Journal of Medical Science Feb 2012HCO3- -rich fluid in the pancreatic juice (2-3 L/day) is secreted by epithelial cells lining the pancreatic duct tree, while digestive enzymes are secreted by acinar... (Review)
Review
HCO3- -rich fluid in the pancreatic juice (2-3 L/day) is secreted by epithelial cells lining the pancreatic duct tree, while digestive enzymes are secreted by acinar cells with a small amount of Cl- -rich fluid. Ductal HCO3- secretion is not only regulated by gastrointestinal hormones and cholinergic nerves but is also influenced by luminal factors: intraductal pressure, Ca2+ concentration, pathological activation of protease and bile reflux. The maximum HCO3- concentration of the juice under secretin stimulation reaches 140-150 mM. Thus pancreatic duct cells secrete HCO3- against a approximately 7-fold concentration gradient. HCO3- secretion critically depends on the activity of CFTR, a cAMP-dependent anion channel localized in the apical membrane of various epithelia. In the proximal part of pancreatic ducts close to acinar cells HCO3 secretion across the apical membrane is largely mediated by SLC26A6 CI- -HCO3- exchanger. In distal ducts where the luminal HCO3- concentration is already high, most of the HCO3- secretion is mediated by HCO3- conductance of CFTR. CFTR is the causative gene for cystic fibrosis. Loss of function due to severe mutations in both alleles causes typical cystic fibrosis characterized by dehydrated, thick, and viscous luminal fluid/mucus in the respiratory and gastrointestinal tract, pancreatic duct, and vas deferens. A compound heterozygote of mutations/polymorphisms (causing a mild dysfunction of CFTR) involves a risk of developing CFTR-related diseases such as chronic pancreatitis. In cystic fibrosis and certain cases of chronic pancreatitis, the pancreatic duct epithelium secretes a small amount of fluid with neutral-acidic pH, which causes an obstruction of the duct lumen by a protein plug or viscous mucus.
Topics: Animals; Bicarbonates; Biological Transport, Active; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Cells; Ethanol; Glucose; Humans; Pancreatic Diseases; Pancreatic Ducts; Pancreatic Juice
PubMed: 22515107
DOI: No ID Found -
Biochemical and Biophysical Research... Jun 2020Secretion of PDI from platelets and endothelial cells is an important step of all thrombotic events. In the absence of extracellular PDI thrombus formation and fibrin...
Secretion of PDI from platelets and endothelial cells is an important step of all thrombotic events. In the absence of extracellular PDI thrombus formation and fibrin generation may be impaired. Thrombin-mediated PDI secretion is regulated by the stimulation of P2Y receptors. This paper provides evidences that P2Y antagonists or AR agonists may modulate release of PDI molecules from platelets and with less efficiency from endothelial cells. Moreover P2Y antagonization or AR agonization modulates platelet-endothelial interaction. We prove that combinations of P2Y antagonists and AR agonists inhibit platelet-dependent adhesion of cancer cells to endothelium and attenuate cancer cell invasiveness, but longer exposition to AR agonists may stimulate migration of invasive breast cancer cells through endothelium thus leading to increased metastasis.
Topics: Androgen Receptor Antagonists; Blood Platelets; Blood Specimen Collection; Bodily Secretions; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Endothelial Cells; Endothelium; Female; Fibrin; Humans; Neoplasm Metastasis; Platelet Adhesiveness; Protein Disulfide-Isomerases; Purinergic P2Y Receptor Antagonists; Receptors, Androgen; Receptors, Purinergic P2Y12; Signal Transduction; Sulfhydryl Compounds; Thrombin; Thrombosis
PubMed: 32265027
DOI: 10.1016/j.bbrc.2020.03.143 -
Scientific Reports Sep 2020Malpighian tubules, analogous to vertebrate nephrons, play a key role in insect osmoregulation and detoxification. Tubules can become infected with a protozoan,...
Malpighian tubules, analogous to vertebrate nephrons, play a key role in insect osmoregulation and detoxification. Tubules can become infected with a protozoan, Malpighamoeba, which damages their epithelial cells, potentially compromising their function. Here we used a modified Ramsay assay to quantify the impact of Malpighamoeba infection on fluid secretion and P-glycoprotein-dependent detoxification by desert locust Malpighian tubules. Infected tubules have a greater surface area and a higher fluid secretion rate than uninfected tubules. Infection also impairs P-glycoprotein-dependent detoxification by reducing the net rhodamine extrusion per surface area. However, due to the increased surface area and fluid secretion rate, infected tubules have similar total net extrusion per tubule to uninfected tubules. Increased fluid secretion rate of infected tubules likely exposes locusts to greater water stress and increased energy costs. Coupled with reduced efficiency of P-glycoprotein detoxification per surface area, Malpighamoeba infection is likely to reduce insect survival in natural environments.
Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Amebiasis; Amoebida; Animals; Biological Transport; Bodily Secretions; Epithelial Cells; Grasshoppers; Infections; Malpighian Tubules; Water-Electrolyte Balance
PubMed: 32994425
DOI: 10.1038/s41598-020-72598-z -
The Yale Journal of Biology and Medicine 1997Glutathione (GSH) plays a critical role in many cellular processes, including the metabolism and detoxification of oxidants, metals, and other reactive electrophilic... (Review)
Review
Glutathione (GSH) plays a critical role in many cellular processes, including the metabolism and detoxification of oxidants, metals, and other reactive electrophilic compounds of both endogenous and exogenous origin. Because the liver is a major site of GSH and glutathione S-conjugate biosynthesis and export, significant effort has been devoted to characterizing liver cell sinusoidal and canalicular membrane transporters for these compounds. Glutathione S-conjugates synthesized in the liver are secreted preferentially into bile, and recent studies in isolated canalicular membrane vesicles indicate that there are multiple transport mechanisms for these conjugates, including those that are energized by ATP hydrolysis and those that may be driven by the electrochemical gradient. Glutathione S-conjugates that are relatively hydrophobic or have a bulky S-substituent are good substrates for the canalicular ATP-dependent transporter mrp2 (multidrug resistance-associated protein 2, also called cMOAT, the canalicular multispecific organic anion transporter, or cMrp, the canalicular isoform of mrp). In contrast with the glutathione S-conjugates, hepatic GSH is released into both blood and bile. GSH transport across both of these membrane domains is of low affinity and is energized by the electrochemical potential. Recent reports describe two candidate GSH transport proteins for the canalicular and sinusoidal membranes (RcGshT and RsGshT, respectively); however, some concerns have been raised regarding these studies. Additional work is needed to characterize GSH transporters at the functional and molecular level.
Topics: Adenosine Triphosphate; Animals; Anion Transport Proteins; Bile; Biological Transport, Active; Carrier Proteins; Glutathione; Homeostasis; Humans; Liver
PubMed: 9626749
DOI: No ID Found -
Cold Spring Harbor Perspectives in... Nov 2012Our model of the MUC2 mucin shows a well-organized netlike gel that is cross-linked by six different covalent and noncovalent bonds. When the MUC2 mucin is packed in the... (Review)
Review
Our model of the MUC2 mucin shows a well-organized netlike gel that is cross-linked by six different covalent and noncovalent bonds. When the MUC2 mucin is packed in the mucin granule it is organized by an amino-terminal concatenated ring platform formed at high calcium and low pH. This packing allows an ordered release and a normal mucin expansion when calcium is removed and pH increased by bicarbonate. This process is defective in the absence of cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate transport. The expanded secreted mucin is suggested to be self-organizing by properties inherited in the MUC2 mucin and by proteolytic processes.
Topics: Bicarbonates; Gels; Glycosylation; Humans; Mucin-2; Mucins; Mucus; Polysaccharides; Protein Conformation
PubMed: 23125206
DOI: 10.1101/cshperspect.a014159 -
MSphere Dec 2020In yeast, many proteins are found in both the cytoplasmic and extracellular compartments, and consequently it can be difficult to distinguish nonconventional secretion...
In yeast, many proteins are found in both the cytoplasmic and extracellular compartments, and consequently it can be difficult to distinguish nonconventional secretion from cellular leakage. Therefore, we monitored the extracellular glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity of intact cells as a specific marker for nonconventional secretion. Extracellular GAPDH activity was proportional to the number of cells assayed, increased with incubation time, and was dependent on added substrates. Preincubation of intact cells with 100 μM dithiothreitol increased the reaction rate, consistent with increased access of the enzyme after reduction of cell wall disulfide cross-links. Such treatment did not increase cell permeability to propidium iodide, in contrast to effects of higher concentrations of reducing agents. An amine-specific membrane-impermeant biotinylation reagent specifically inactivated extracellular GAPDH. The enzyme was secreted again after a 30- to 60-min lag following the inactivation, and there was no concomitant increase in propidium iodide staining. There were about 4 × 10 active GAPDH molecules per cell at steady state, and secretion studies showed replenishment to that level 1 h after inactivation. These results establish conditions for specific quantitative assays of cell wall proteins in the absence of cytoplasmic leakage and for subsequent quantification of secretion rates in intact cells. Eukaryotic cells secrete many proteins, including many proteins that do not follow the classical secretion pathway. Among these, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is unexpectedly found in the walls of yeasts and other fungi and in extracellular space in mammalian cell cultures. It is difficult to quantify extracellular GAPDH, because leakage of just a little of the very large amount of cytoplasmic enzyme can invalidate the determinations. We used enzymatic assays of intact cells while also maintaining membrane integrity. The results lead to estimates of the amount of extracellular enzyme and its rate of secretion to the wall in intact cells. Therefore, enzyme assays under controlled conditions can be used to investigate nonconventional secretion more generally.
Topics: Bodily Secretions; Cell Membrane Permeability; Cell Wall; Cytoplasm; Flow Cytometry; Glyceraldehyde-3-Phosphate Dehydrogenases; Saccharomyces cerevisiae
PubMed: 33328349
DOI: 10.1128/mSphere.01027-20 -
Marine Drugs Sep 2018Jellyfish respond quickly to external stress that stimulates mucus secretion as a defense. Neither the composition of secreted mucus nor the process of secretion are...
BACKGROUND
Jellyfish respond quickly to external stress that stimulates mucus secretion as a defense. Neither the composition of secreted mucus nor the process of secretion are well understood.
METHODS
jellyfish were stimulated by removing them from environmental seawater. Secreted mucus and tissue samples were then collected within 60 min, and analyzed by a combination of proteomics and metabolomics using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), respectively.
RESULTS
Two phases of sample collection displayed a quick decrease in volume, followed by a gradual increase. A total of 2421 and 1208 proteins were identified in tissue homogenate and secreted mucus, respectively. Gene Ontology (GO) analysis showed that the mucus-enriched proteins are mainly located in extracellular or membrane-associated regions, while the tissue-enriched proteins are distributed throughout intracellular compartments. Tryptamine, among 16 different metabolites, increased with the largest-fold change value of 7.8 in mucus, which is consistent with its involvement in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway 'tryptophan metabolism'. We identified 11 metalloproteinases, four serpins, three superoxide dismutases and three complements, and their presence was speculated to be related to self-protective defense.
CONCLUSIONS
Our results provide a composition profile of proteins and metabolites in stress-induced mucus and tissue homogenate of This provides insight for the ongoing endeavors to discover novel bioactive compounds. The large increase of tryptamine in mucus may indicate a strong stress response when jellyfish were taken out of seawater and the active self-protective components such as enzymes, serpins and complements potentially play a key role in innate immunity of jellyfish.
Topics: Animals; Chromatography, High Pressure Liquid; Complement System Proteins; Enzymes; Immunity, Innate; Metabolomics; Mucus; Proteomics; Scyphozoa; Serpins; Stress, Physiological; Tandem Mass Spectrometry
PubMed: 30231483
DOI: 10.3390/md16090341 -
Cells Jan 2024MRGPRX2, the human member of the MAS-related G-protein-coupled receptors (GPCRs), mediates the immunoglobulin E (IgE)-independent responses of a subset of mast cells...
MRGPRX2, the human member of the MAS-related G-protein-coupled receptors (GPCRs), mediates the immunoglobulin E (IgE)-independent responses of a subset of mast cells (MCs) that are associated with itch, pain, neurogenic inflammation, and pseudoallergy to drugs. The mechanisms underlying the responses of MRGPRX2 to its multiple and diverse ligands are still not completely understood. Given the close association between GPCR location and function, and the key role played by Rab GTPases in controlling discrete steps along vesicular trafficking, we aimed to reveal the vesicular pathways that directly impact MRGPRX2-mediated exocytosis by identifying the Rabs that influence this process. For this purpose, we screened 43 Rabs for their functional and phenotypic impacts on MC degranulation in response to the synthetic MRGPRX2 ligand compound 48/80 (c48/80), which is often used as the gold standard of MRGPRX2 ligands, or to substance P (SP), an important trigger of neuroinflammatory MC responses. Results of this study highlight the important roles played by macropinocytosis and autophagy in controlling MRGPRX2-mediated exocytosis, demonstrating a close feedback control between the internalization and post-endocytic trafficking of MRGPRX2 and its triggered exocytosis.
Topics: Humans; Bodily Secretions; Exocytosis; Autophagy; Immunoglobulin E; Inflammation; Secretory Vesicles; Nerve Tissue Proteins; Receptors, Neuropeptide; Receptors, G-Protein-Coupled
PubMed: 38201297
DOI: 10.3390/cells13010093 -
Journal of Bacteriology Jun 2017and many related bacteria secrete proteins across the outer membrane using the type IX secretion system (T9SS). Proteins secreted by T9SSs have amino-terminal signal...
and many related bacteria secrete proteins across the outer membrane using the type IX secretion system (T9SS). Proteins secreted by T9SSs have amino-terminal signal peptides for export across the cytoplasmic membrane by the Sec system and carboxy-terminal domains (CTDs) targeting them for secretion across the outer membrane by the T9SS. Most but not all T9SS CTDs belong to the family TIGR04183 (type A CTDs). We functionally characterized diverse CTDs for secretion by the T9SS. Attachment of the CTDs from RemA, AmyB, and ChiA to the foreign superfolder green fluorescent protein (sfGFP) that had a signal peptide at the amino terminus resulted in secretion across the outer membrane. In each case, approximately 80 to 100 amino acids from the extreme carboxy termini were needed for efficient secretion. Several type A CTDs from distantly related members of the phylum functioned in , supporting the secretion of sfGFP by the T9SS. SprB requires the T9SS for secretion but lacks a type A CTD. It has a conserved C-terminal domain belonging to the family TIGR04131, which we refer to as a type B CTD. The CTD of SprB was required for its secretion, but attachment of C-terminal regions of SprB of up to 1,182 amino acids to sfGFP failed to result in secretion. Additional features outside the C-terminal region of SprB may be required for its secretion. Type IX protein secretion systems (T9SSs) are common in but limited to members of the phylum Most proteins that are secreted by T9SSs have conserved carboxy-terminal domains that belong to the protein domain family TIGR04183 (type A CTDs) or TIGR04131 (type B CTDs). Here, we identify features of T9SS CTDs of that are required for protein secretion and demonstrate that type A CTDs from distantly related members of the phylum function with the T9SS to secrete the foreign protein sfGFP. In contrast, type B CTDs failed to target sfGFP for secretion, suggesting a more complex association with the T9SS.
Topics: Bacterial Proteins; Bacterial Secretion Systems; Flavobacterium; Protein Domains; Protein Sorting Signals; Protein Transport
PubMed: 28396348
DOI: 10.1128/JB.00884-16 -
European Journal of Immunology Sep 2011
Review
Topics: Animals; Atherosclerosis; Bodily Secretions; Cytokines; Cytotoxicity, Immunologic; Homeostasis; Humans; Immunity, Innate; Infections; Inflammation; Leukocytes, Mononuclear; Macrophages; Neoplasms; Phagocytes; Phagocytosis
PubMed: 21952798
DOI: 10.1002/eji.201141988