Academic literature on the topic 'Secretory granula'
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Journal articles on the topic "Secretory granula"
1
von Zglinicki, Thomas, and Godfried M. Roomans. "X-Ray Microanalysis of the Intestine: Identification of Electrolyte Secreting Cells." Proceedings, annual meeting, Electron Microscopy Society of America 48, no. 2 (August 12, 1990): 342–43. http://dx.doi.org/10.1017/s0424820100135319.
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Frozen dried cryosections of mouse jejunum were investigated. Besides Paneth and Goblet cells, two different types of crypt enterocytes could be distinguished according to clearly different electrolyte concentrations and to the presence (type A) or absence (type B) of small secretion granula in the cytoplasm.Secretion was stimulated by an intraperitoneal injection of either isoproterenol or pilocarpine. In some experiments, isoproterenol stimulation was blocked by alloxan, a potent inhibitor of the adenylate cyclase. Changes of cytoplasmic element concentrations were measured in frozen dried cryosections. In addition, the water content of the cells was measured by fully quantitative bulk specimen x-ray microanalysis.It was expected that actively secreting cells should display a decrease of Cl concentrations. This behaviour was confirmed in crypt A cells exclusively (Fig. 1). Therefore, it was concluded that crypt A cells are the main secretory cells in the intestinal epithelium.The water content of all epithelial cells in the intestine was found to increase under pilocarpine stimulation and to decrease under isoproterenol stimulation (Fig. 2).
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Cossu, M., M. S. Lantini, and R. Puxeddu. "Immunocytochemical localization of Lewis blood group antigens in human salivary glands." Journal of Histochemistry & Cytochemistry 42, no. 8 (August 1994): 1135–42. http://dx.doi.org/10.1177/42.8.8027532.
Full textAbstract:
We demonstrated the immunohistochemical distribution of Le-a and Le-b blood group antigens in human major and minor salivary glands at the ultrastructural level by applying a post-embedding immunogold staining method. In secretors' glands, a faint Le-a reactivity was found only in mucous droplets, whereas Le-b antigen was intensely stained in secretory granules of most mucous cells, in those of intercalated duct cells, in the pale granular matrix of some serous cells, and, when osmication was omitted, in cytoplasmatic vesicles and cell surfaces of striated ducts. In the submandibular gland of a non-secretor, Le-a antigen was considerably stained in mucous droplets, whereas Le-b reactivity was restricted to the striated duct cells. These results indicate that the secretor status affects the secretion of Lewis antigens by mucous, serous, and intercalated duct cells but not the presence of Le-b as a surface antigen in striated duct cells.
3
Skott, O. "Do osmotic forces play a role in renin secretion?" American Journal of Physiology-Renal Physiology 255, no. 1 (July 1, 1988): F1—F10. http://dx.doi.org/10.1152/ajprenal.1988.255.1.f1.
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Secretory granules swell during exocytosis. Swelling may follow fusion and assist in extrusion of the granular content, or swelling may cause granular fusion with the plasmalemma. A granular proton gradient has been suggested to be involved in such preexocytic granular swelling. Exocytosis of renin from juxtaglomerular cells of isolated preparations is very sensitive to changes in the extracellular osmolality. Extracellular hyposmolality causes swelling of secretory granules, fusions between peripherally located granules and plasmalemma, and an increased number of release episodes. Induction of granule swelling at constant extracellular osmolality also stimulates renin release. Newly recruited renin granules are osmosensitive, and a high extracellular osmolality blocks secretion induced by other means (low calcium). Dissipation of granular proton gradients inhibits renin release without affecting the osmosensitivity. Thus, in renin release in vitro, a granular swelling precedes fusion and exocytosis, and a granular proton gradient may contribute to preexocytic swelling when extracellular osmolality is constant. The osmosensitivity may be important for macula densamediated renin release.
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Barg, Sebastian, Ping Huang, Lena Eliasson, Deborah J. Nelson, Stefanie Obermüller, Patrik Rorsman, Frank Thévenod, and Erik Renström. "Priming of insulin granules for exocytosis by granular Cl− uptake and acidification." Journal of Cell Science 114, no. 11 (June 1, 2001): 2145–54. http://dx.doi.org/10.1242/jcs.114.11.2145.
Full textAbstract:
ATP-dependent priming of the secretory granules precedes Ca2+-regulated neuroendocrine secretion, but the exact nature of this reaction is not fully established in all secretory cell types. We have further investigated this reaction in the insulin-secreting pancreatic B-cell and demonstrate that granular acidification driven by a V-type H+-ATPase in the granular membrane is a decisive step in priming. This requires simultaneous Cl− uptake through granular ClC-3 Cl− channels. Accordingly, granule acidification and priming are inhibited by agents that prevent transgranular Cl− fluxes, such as 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) and an antibody against the ClC-3 channels, but accelerated by increases in the intracellular ATP:ADP ratio or addition of hypoglycemic sulfonylureas. We suggest that this might represent an important mechanism for metabolic regulation of Ca2+-dependent exocytosis that is also likely to be operational in other secretory cell types.
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Kemter, Elisabeth, Andreas Müller, Martin Neukam, Anna Ivanova, Nikolai Klymiuk, Simone Renner, Kaiyuan Yang, et al. "Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs." Proceedings of the National Academy of Sciences 118, no. 37 (September 10, 2021): e2107665118. http://dx.doi.org/10.1073/pnas.2107665118.
Full textAbstract:
β cells produce, store, and secrete insulin upon elevated blood glucose levels. Insulin secretion is a highly regulated process. The probability for insulin secretory granules to undergo fusion with the plasma membrane or being degraded is correlated with their age. However, the molecular features and stimuli connected to this behavior have not yet been fully understood. Furthermore, our understanding of β cell function is mostly derived from studies of ex vivo isolated islets in rodent models. To overcome this translational gap and study insulin secretory granule turnover in vivo, we have generated a transgenic pig model with the SNAP-tag fused to insulin. We demonstrate the correct targeting and processing of the tagged insulin and normal glycemic control of the pig model. Furthermore, we show specific single- and dual-color granular labeling of in vivo–labeled pig pancreas. This model may provide unprecedented insights into the in vivo insulin secretory granule behavior in an animal close to humans.
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Burgoyne, Robert D., and Alan Morgan. "Secretory Granule Exocytosis." Physiological Reviews 83, no. 2 (April 1, 2003): 581–632. http://dx.doi.org/10.1152/physrev.00031.2002.
Full textAbstract:
Regulated exocytosis of secretory granules or dense-core granules has been examined in many well-characterized cell types including neurons, neuroendocrine, endocrine, exocrine, and hemopoietic cells and also in other less well-studied cell types. Secretory granule exocytosis occurs through mechanisms with many aspects in common with synaptic vesicle exocytosis and most likely uses the same basic protein components. Despite the widespread expression and conservation of a core exocytotic machinery, many variations occur in the control of secretory granule exocytosis that are related to the specialized physiological role of particular cell types. In this review we describe the wide range of cell types in which regulated secretory granule exocytosis occurs and assess the evidence for the expression of the conserved fusion machinery in these cells. The signals that trigger and regulate exocytosis are reviewed. Aspects of the control of exocytosis that are specific for secretory granules compared with synaptic vesicles or for particular cell types are described and compared to define the range of accessory control mechanisms that exert their effects on the core exocytotic machinery.
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Tooze, John. "Secretory granule formation." Cell Biophysics 19, no. 1 (October 1991): 117–30. http://dx.doi.org/10.1007/bf02989885.
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Möhn, H., V. Le Cabec, S. Fischer, and I. Maridonneau-Parini. "The src-family protein-tyrosine kinase p59hck is located on the secretory granules in human neutrophils and translocates towards the phagosome during cell activation." Biochemical Journal 309, no. 2 (July 15, 1995): 657–65. http://dx.doi.org/10.1042/bj3090657.
Full textAbstract:
The src-family protein-tyrosine kinase p59hck is mainly expressed in neutrophils; however, its functional role in these cells is unknown. Several other src-family members are localized on secretory vesicles and have been proposed to regulate intracellular traffic. We have established here the subcellular localization of p59hck in human neutrophils. Immunoblotting of subcellular fractions showed that approx. 60% of the p59hck per cell is localized on the secretory granules; the other 40% is distributed equally between non-granular membranes and the cytosol. Immunofluorescence of neutrophils and HL60 cells suggests that the p59hck-positive granules are azurophil granules. Granular p59hck is highly susceptible to degradation by an azurophil-granule proteinase. Different forms of p59hck occur in the three subcellular compartments: a 61 kDa form is mainly found in the granules, a 59 kDa form is predominant in the non-granular membranes, whereas cytosolic p59hck migrates as a doublet at 63 kDa. During the process of phagocytosis-linked degranulation, induced by serum-opsonized zymosan in neutrophils or HL60 cells, granular p59hck translocates towards the phagosome. The subcellular localization of p59hck suggests that the enzyme could be involved in the regulation of the degranulation process.
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Alvarez de Toledo, G., and J. M. Fernandez. "Patch-clamp measurements reveal multimodal distribution of granule sizes in rat mast cells." Journal of Cell Biology 110, no. 4 (April 1, 1990): 1033–39. http://dx.doi.org/10.1083/jcb.110.4.1033.
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Using patch-clamp techniques, we have followed the attributes of the secretory granules of peritoneal mast cells obtained from rats of different ages. The granule attributes were determined by following the step increases in the cell surface membrane area caused by the exocytosis of the granules in GTP gamma S stimulated mast cells. Our data show that the amount of granule membrane available for exocytosis depends exponentially on the weight (age) of the donor rat, reaching a maximum at approximately 300 g. The data are consistent with an exponential growth in the number of granules contained by mast cells of maturing animals. Histograms of the sizes of the step increases in surface area caused by exocytosis of the granules showed at least four equally spaced peaks of similar variance where the position of the first peak and the spacing between peaks averaged 1.3 +/- 0.4 micron2. In all cells recorded, no more than seven peaks could be found, the higher order peaks having a lower probability of occurrence. The distribution of granule sizes did not change measurably between young and adult animals. This study suggests that at least two separate steps may determine the size of a secretory granule: granule to granule fusion that may account for the subunit composition of granule sizes and traffic of microvesicles through the maturing granules that may account for the variance observed in the granule sizes. This study also demonstrates a novel way to study granulo-genesis in living cells.
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Sano, K., S. Waguri, N. Sato, E. Kominami, and Y. Uchiyama. "Coexistence of renin and cathepsin B in secretory granules of granular duct cells in male mouse submandibular gland." Journal of Histochemistry & Cytochemistry 41, no. 3 (March 1993): 433–38. http://dx.doi.org/10.1177/41.3.8429206.
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Cathepsin B, a representative lysosomal cysteine proteinase, has been demonstrated to coexist with renin in secretary granules of rat pituitary LH/FSH cells and renal juxtaglomerular cells. We investigated immunocytochemically the localization of cathepsins B, H, and L in the submandibular gland of male mice, in which active renin is also produced. By light microscopy, granular immunodeposits for cathepsin B were detected in epithelial cells of the gland, particularly in granular duct cells and interstitial cells. Immunoreactivity for cathepsins H and L was mainly found in interstitial cells, although that for cathepsin H was weakly seen in acinar cells. By electron microscopy, immunogold particles indicating cathepsin B intensely labeled small granules near the Golgi complex of granular duct cells and weakly labeled large secretory granules, whereas those showing renin labeled both granules. Double immunostaining co-localized immunogold particles showing renin and cathepsin B in small perinuclear granules near the Golgi complex. Some immunopositive granules seemed to be closely associated with the Golgi elements. These results indicate that the co-localization of renin and cathepsin B is also seen in secretory granules of granular duct cells in the mouse submandibular gland, as seen in rat juxtaglomerular and LH/FSH cells. This suggests that cathepsin B is one of the possible candidates for the renin-processing enzyme.
Dissertations / Theses on the topic "Secretory granula"
1
Schubert, Sandra. "The Role of [beta]2-Syntrophin Phosphorylation in Secretory Granule Exocytosis." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2006. http://nbn-resolving.de/urn:nbn:de:swb:14-1146851994562-42414.
Full textAbstract:
The trafficking of insulin secretory granules(SGs) of pancreatic b-cells is a tightly controlled complex network. Increasing evidence indicates that the cortical actin cytoskeleton modulates the mobility and exocytosis of SGs,yet the mechanisms anchoring SGs to the cytoskeleton is not completely understood.It has been shown by Ort et al.(2000,2001) that the cytoplasmic tail of an intrinsic membrane protein of the SGs named ICA512/IA-2 binds the PDZ domain of b2-syntrophin,which in turn binds to the F-actin-binding protein utrophin. These data also indicate that stimulation of SG exocytosis affects the phosphorylation of b2-syntrophin,hence altering its binding to ICA512.Therefore a model was proposed whereby SGs are anchored to the actin cytoskeleton through the ICA512/b2-syntrophin complex, whose dynamics are regulated by phosphorylation.To test this model GFP-b2-syntrophin stable INS-1 cell clones were generated.GFP-b2-syntrophin expression and localization pattern were similar to those of the endogenous protein. Electron microscopy showed that in GFP-b2-syntrophin INS-1 cells the number of SGs with a pear-like shape was increased relative to control cells. Insulin content and stimulated secretion were increased in three GFP-â2-syntrophin INS-1 cell clones,compared to non-transfected INS-1 cells and INS-1 cells expressing GFP. These increments correlated with the different expression levels of GFP-b2-syntrophin in the three GFP-b2-syntrophin INS-1 cell clones. These findings support the hypothesis that b2-syntrophin regulates the trafficking and exocytosis of SGs by modulating their tethering to the actin cytoskeleton.In order to confirm the proposed model, the phosphorylation of b2-syntrophin was investigated in more detail. Similar to endogenous b2-syntrophin,GFP-b2-syntrophin underwent Ca2+-dependent and okadaic acid-sensitive dephosphorylation upon stimulation of insulin secretion. Stimulation-dependent dephosphorylation was confirmed by immunoprecipitation of 32P-labeled GFP-b2-syntrophin.Mass spectrometry of immunoprecipitated GFP-b2-syntrophin allowed the identification of four serine-phosphorylation sites (S75,S90,S213,S373) that could affect the binding to ICA512.Mutants,in which all four phosphoserines, were replaced by either asp or ala to mimic(S/D) or prevent(S/A) phosphorylation were expressed in INS-1 cells. All S/D mutants retained a cortical localization,but by immunoblotting the pattern of the S75D allele differed from wild type and all other S/D alleles.Conversely, all S/A alleles were diffused cytosolically, except S213A,which was still restricted to the cortex. Finally, pull down assays showed increased binding of ICA512 to the S75A and S90D alleles compared to wild type b2-syntrophin,while the opposite was observed with the S75D and S90A mutants.Additionally,both the S75 and the S213 allele conform a consensus for phosphorylation by Cdk5,which is known to modulate insulin secretion. The phosphorylation of GFP-b2-syntrophin and particularly the S75 allele by Cdk5 was exhibited with pharmacological inhibitors,by in vitro phosphorylation and by RNAi. Taken together, these findings are consistent with the model by which phosphorylation of b2-syntrophin modulates the tethering of SGs to the cytoskeleton, and thereby their mobility and exocytosis. Specifically, the data of this thesis suggest that Cdk5-dependent phosphorylation of the S75 site of GFP-b2-syntrophin facilitates insulin secretion by reducing the interaction of b2-syntrophin with ICA512,thereby decreasing the actin cytoskeleton constrain on SG mobility. This process could occur in combination with the phosphatase-dependent dephosphorylation of b2-syntrophin at phosphosites other than S75Der Transport Insulin-gefüllter sekretorische Granula(SG) ist ein streng kontrollierter komplexer Prozess.Es gibt vermehrt Beweise,dass das kortikale Actinzytoskelett die Ausschüttung der SGs beeinflusst.Bisher ist der Mechanismus der Verankerung von SGs am Zytoskelett noch nicht vollständig aufgeklärt.Ort et al.(2000,2001) haben gezeigt,daß der zytosoplasmatische Teil des trans-membranen SG-Proteins ICA512 mit der PDZ-Domäne von b2-Syntrophin interagiert.Dieses Protein bindet das F-Actin-Bindeprotein Utrophin.Die Ergebnisse zeigen außerdem,daß durch Stimulation der SG-Exozytose der Phosphorilierungsstatus von b2-Syntrophin beeinflusst wird,woraus ein verändertes Bindungsvermögen zu ICA512 resultiert.Es wurde ein Funktionsmodel vorgestellt,in dem sich SGs durch die Interaktion des ICA512/b2-Syntrophin Komplexes an das Actinzytoskelett binden.Dabei wird die Bindedynamik durch Phosphorilierung reguliert.Um dieses Model zu etablieren,wurden stabile GFP-b2-Syntrophin produzierende INS-1-Zellklone erzeugt.Die zelluläre Lokalisation und das Expressionsmuster von GFP-b2-Syntrophin stimmen mit dem des endogenen Proteins überein.Elektronenmikroskopie zeigte eine größe Anzahl oval-verformter SGs in GFP-b2-Syntrophin INS-1-Zellen im Vergleich zu Kontrollzellen.Verglichen mit nicht-transfizierten INS-1 Zellen waren in drei GFP-b2-Syntrophin INS-1-Zellklonen der Insulingehalt der Zellen und die stimulierte Insulinsekretion erhöht.Die Werte korrelierten mit den unterschiedlichen GFP-b2-Syntrophin Expressionsmengen der Klone.Diese Ergebnisse untermauern die Hypothese,daß b2-Syntrophin den Transport und die Sekretion der SGs durch Modulation ihres Bindevermögens an Actin reguliert.Um das postulierte Model genauer zu prüfen,wurde die Phosphorilierung von b2-Syntrophin detaillierter untersucht.Das GFP-Protein wurde,ähnlich dem endogenen b2-Syntrophin,durch Stimulation der Insulinausschüttung dephosphoriliert.Diese Dephosphorilierung ist Ca2+-abhängig und Okadeinsäuresensitiv.Die stimulationsabhängige Dephosphorilierung wurde durch Immunoprezipitation von 32P-markiertem GFP-b2-Syntrophin bestätigt.Massenspektrometrie des präzipitierten Proteins ermöglichte die Identifikation von vier Serin-Phosphorilierungsstellen(S75,S90,S213,S373),welche die Bindung zu ICA512 beeinflussen könnten.Mutanten,in denen die vier Phosphoserine durch Asp beziehungsweise Ala ersetzt wurden,um entweder eine Phosphorilierung(S/D) oder Dephosphorilierung(S/A) nachzuahmen,wurden in INS-1-Zellen exprimiert.Alle S/D Mutanten blieben kortikal lokalisiert.Das Expressionsmuster des S75D Allels unterschied sich jedoch von denen des Wild-Typs(wt).Im Gegensatz dazu waren alle S/A Allele zytosolisch verteilt.Eine Ausnahme bildete S213A,das an der Zellkortex lokalisiert blieb.Im Vergleich zu wt b2-Syntrophin zeigten PullDown-Assays eine erhöhte Bindung von ICA512 zu den S75A und S90D Allelen.Das Gegenteil konnte für die S75D und S90A Mutanten nachgewiesen werden.S75,S90 und S213 sind in einer Konsensussequenz für Cdk5-Phosphorilierung enthalten.Diese Kinase kann die Insulinsekretion regulieren.Die Phosphorilierung von b2-Syntrophin,insbesondere des S75 Allels durch Cdk5 wurde durch pharmakologische Inhibitoren,in vitro-Phosphorilierung und RNAi demonstriert.Zusammenfassend stimmen diese Erkenntnisse mit dem Model überein,daß die Phosphorilierung von b2-Syntrophin die Vernetzung von SGs mit Actin und dadurch deren Mobilität und Exozytose moduliert.Im Speziellen postulieren die Ergebnisse dieser Arbeit eine Cdk5-abhängige Phosphorilierung der S75 Stelle des b2-Syntrophins.Durch eine verminderte Interaktion von b2-Syntrophin und ICA512 erleichtert diese Mutante vermutlich die Insulinsekretion,da der Einfluss des Actinzytoskeletts auf die Granulamobilität vermindert ist.Dieser Prozess ereignet sich möglicherweise in Kombination mit einer Dephosphorilierung des b2-Syntrophins.in Kombination mit einer Dephosphorilierung des b2-Syntrophins
2
Schubert, Sandra. "The Role of [beta]2-Syntrophin Phosphorylation in Secretory Granule Exocytosis." Doctoral thesis, Technische Universität Dresden, 2005. https://tud.qucosa.de/id/qucosa%3A23710.
Full textAbstract:
The trafficking of insulin secretory granules(SGs) of pancreatic b-cells is a tightly controlled complex network. Increasing evidence indicates that the cortical actin cytoskeleton modulates the mobility and exocytosis of SGs,yet the mechanisms anchoring SGs to the cytoskeleton is not completely understood.It has been shown by Ort et al.(2000,2001) that the cytoplasmic tail of an intrinsic membrane protein of the SGs named ICA512/IA-2 binds the PDZ domain of b2-syntrophin,which in turn binds to the F-actin-binding protein utrophin. These data also indicate that stimulation of SG exocytosis affects the phosphorylation of b2-syntrophin,hence altering its binding to ICA512.Therefore a model was proposed whereby SGs are anchored to the actin cytoskeleton through the ICA512/b2-syntrophin complex, whose dynamics are regulated by phosphorylation.To test this model GFP-b2-syntrophin stable INS-1 cell clones were generated.GFP-b2-syntrophin expression and localization pattern were similar to those of the endogenous protein. Electron microscopy showed that in GFP-b2-syntrophin INS-1 cells the number of SGs with a pear-like shape was increased relative to control cells. Insulin content and stimulated secretion were increased in three GFP-â2-syntrophin INS-1 cell clones,compared to non-transfected INS-1 cells and INS-1 cells expressing GFP. These increments correlated with the different expression levels of GFP-b2-syntrophin in the three GFP-b2-syntrophin INS-1 cell clones. These findings support the hypothesis that b2-syntrophin regulates the trafficking and exocytosis of SGs by modulating their tethering to the actin cytoskeleton.In order to confirm the proposed model, the phosphorylation of b2-syntrophin was investigated in more detail. Similar to endogenous b2-syntrophin,GFP-b2-syntrophin underwent Ca2+-dependent and okadaic acid-sensitive dephosphorylation upon stimulation of insulin secretion. Stimulation-dependent dephosphorylation was confirmed by immunoprecipitation of 32P-labeled GFP-b2-syntrophin.Mass spectrometry of immunoprecipitated GFP-b2-syntrophin allowed the identification of four serine-phosphorylation sites (S75,S90,S213,S373) that could affect the binding to ICA512.Mutants,in which all four phosphoserines, were replaced by either asp or ala to mimic(S/D) or prevent(S/A) phosphorylation were expressed in INS-1 cells. All S/D mutants retained a cortical localization,but by immunoblotting the pattern of the S75D allele differed from wild type and all other S/D alleles.Conversely, all S/A alleles were diffused cytosolically, except S213A,which was still restricted to the cortex. Finally, pull down assays showed increased binding of ICA512 to the S75A and S90D alleles compared to wild type b2-syntrophin,while the opposite was observed with the S75D and S90A mutants.Additionally,both the S75 and the S213 allele conform a consensus for phosphorylation by Cdk5,which is known to modulate insulin secretion. The phosphorylation of GFP-b2-syntrophin and particularly the S75 allele by Cdk5 was exhibited with pharmacological inhibitors,by in vitro phosphorylation and by RNAi. Taken together, these findings are consistent with the model by which phosphorylation of b2-syntrophin modulates the tethering of SGs to the cytoskeleton, and thereby their mobility and exocytosis. Specifically, the data of this thesis suggest that Cdk5-dependent phosphorylation of the S75 site of GFP-b2-syntrophin facilitates insulin secretion by reducing the interaction of b2-syntrophin with ICA512,thereby decreasing the actin cytoskeleton constrain on SG mobility. This process could occur in combination with the phosphatase-dependent dephosphorylation of b2-syntrophin at phosphosites other than S75.Der Transport Insulin-gefüllter sekretorische Granula(SG) ist ein streng kontrollierter komplexer Prozess.Es gibt vermehrt Beweise,dass das kortikale Actinzytoskelett die Ausschüttung der SGs beeinflusst.Bisher ist der Mechanismus der Verankerung von SGs am Zytoskelett noch nicht vollständig aufgeklärt.Ort et al.(2000,2001) haben gezeigt,daß der zytosoplasmatische Teil des trans-membranen SG-Proteins ICA512 mit der PDZ-Domäne von b2-Syntrophin interagiert.Dieses Protein bindet das F-Actin-Bindeprotein Utrophin.Die Ergebnisse zeigen außerdem,daß durch Stimulation der SG-Exozytose der Phosphorilierungsstatus von b2-Syntrophin beeinflusst wird,woraus ein verändertes Bindungsvermögen zu ICA512 resultiert.Es wurde ein Funktionsmodel vorgestellt,in dem sich SGs durch die Interaktion des ICA512/b2-Syntrophin Komplexes an das Actinzytoskelett binden.Dabei wird die Bindedynamik durch Phosphorilierung reguliert.Um dieses Model zu etablieren,wurden stabile GFP-b2-Syntrophin produzierende INS-1-Zellklone erzeugt.Die zelluläre Lokalisation und das Expressionsmuster von GFP-b2-Syntrophin stimmen mit dem des endogenen Proteins überein.Elektronenmikroskopie zeigte eine größe Anzahl oval-verformter SGs in GFP-b2-Syntrophin INS-1-Zellen im Vergleich zu Kontrollzellen.Verglichen mit nicht-transfizierten INS-1 Zellen waren in drei GFP-b2-Syntrophin INS-1-Zellklonen der Insulingehalt der Zellen und die stimulierte Insulinsekretion erhöht.Die Werte korrelierten mit den unterschiedlichen GFP-b2-Syntrophin Expressionsmengen der Klone.Diese Ergebnisse untermauern die Hypothese,daß b2-Syntrophin den Transport und die Sekretion der SGs durch Modulation ihres Bindevermögens an Actin reguliert.Um das postulierte Model genauer zu prüfen,wurde die Phosphorilierung von b2-Syntrophin detaillierter untersucht.Das GFP-Protein wurde,ähnlich dem endogenen b2-Syntrophin,durch Stimulation der Insulinausschüttung dephosphoriliert.Diese Dephosphorilierung ist Ca2+-abhängig und Okadeinsäuresensitiv.Die stimulationsabhängige Dephosphorilierung wurde durch Immunoprezipitation von 32P-markiertem GFP-b2-Syntrophin bestätigt.Massenspektrometrie des präzipitierten Proteins ermöglichte die Identifikation von vier Serin-Phosphorilierungsstellen(S75,S90,S213,S373),welche die Bindung zu ICA512 beeinflussen könnten.Mutanten,in denen die vier Phosphoserine durch Asp beziehungsweise Ala ersetzt wurden,um entweder eine Phosphorilierung(S/D) oder Dephosphorilierung(S/A) nachzuahmen,wurden in INS-1-Zellen exprimiert.Alle S/D Mutanten blieben kortikal lokalisiert.Das Expressionsmuster des S75D Allels unterschied sich jedoch von denen des Wild-Typs(wt).Im Gegensatz dazu waren alle S/A Allele zytosolisch verteilt.Eine Ausnahme bildete S213A,das an der Zellkortex lokalisiert blieb.Im Vergleich zu wt b2-Syntrophin zeigten PullDown-Assays eine erhöhte Bindung von ICA512 zu den S75A und S90D Allelen.Das Gegenteil konnte für die S75D und S90A Mutanten nachgewiesen werden.S75,S90 und S213 sind in einer Konsensussequenz für Cdk5-Phosphorilierung enthalten.Diese Kinase kann die Insulinsekretion regulieren.Die Phosphorilierung von b2-Syntrophin,insbesondere des S75 Allels durch Cdk5 wurde durch pharmakologische Inhibitoren,in vitro-Phosphorilierung und RNAi demonstriert.Zusammenfassend stimmen diese Erkenntnisse mit dem Model überein,daß die Phosphorilierung von b2-Syntrophin die Vernetzung von SGs mit Actin und dadurch deren Mobilität und Exozytose moduliert.Im Speziellen postulieren die Ergebnisse dieser Arbeit eine Cdk5-abhängige Phosphorilierung der S75 Stelle des b2-Syntrophins.Durch eine verminderte Interaktion von b2-Syntrophin und ICA512 erleichtert diese Mutante vermutlich die Insulinsekretion,da der Einfluss des Actinzytoskeletts auf die Granulamobilität vermindert ist.Dieser Prozess ereignet sich möglicherweise in Kombination mit einer Dephosphorilierung des b2-Syntrophins.in Kombination mit einer Dephosphorilierung des b2-Syntrophins.
3
Guest, Paul C. "Insulin secretory granule biogenesis." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304963.
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Bennett, Deborah Louise. "Subtilisin-related proteases of the insulin secretory granule." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319496.
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Urbe, Sylvie. "Molecular mechanisms of secretory granule biogenesis in neuroendocrine cells." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286744.
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Ahras, Malika. "Synaptotagmin IV function in secretory granule maturation in neuroendocrine cells." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445250/.
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In neuroendocrine cells, immature secretory granules (ISGs) bud from the trans Golgi network (TGN), and then undergo a maturation process that includes ISG-ISG homotypic fusion, removal of excess membranes via clathrin-coated vesicles (CCVs) and acidification of the granules. These mature secretory granules (MSGs) can then fuse with the plasma membrane upon receiving an external signal, and finally release their content in the extracellular space. In this thesis, I will present evidence that Synaptotagmin IV (Syt IV) is one of the components involved in the regulation of granule maturation in neuroendocrine cells. Syt IV is a neuron and neuroendocrine cell-specific isoform, which belongs to the synaptotagmin family of membrane trafficking proteins. After confirming that Syt IV is localised on ISGs and absent from MSGs in PCI2 cells, I investigated whether Syt IV is involved in ISG homotypic fusion by adding the purified Syt IV cytoplasmic domain into an in vitro assay, where it functions as a dominant negative. Addition of this domain, but not a similar domain from Syt I, resulted in a dose-dependent inhibition of ISG-ISG fusion. Furthermore, I found that Syt IV binds to the ISG-SNARE Syntaxin 6 (Stx6), suggesting that the two proteins might be part of the same machinery that regulates ISG maturation. In addition, I used an in vivo approach based on the processing of secretogranin II (Sgll) into its degradation product pi8, which occurs during ISG maturation, to assay Syt IV function. I show that the Syt IV cytoplasmic domain, as well as siRNA-mediated knockdown of Syt IV inhibits Sgll processing by prohormone convertase 2 (PC2). Interestingly, PC2 is found mostly in the pro-form, suggesting that activation of PC2 is also inhibited. We conclude that Syt IV is an essential component for the process of secretory granule maturation. Lastly, I found that Syt IV binds preferentially to membrane-bound clathrin adaptor protein-1 (AP-1). This suggests that Syt IV might be sorted from maturing SGs in a complex, possibly via an ISG-SNARE protein that interacts directly with AP-1.
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Wasmeier, Christina. "Molecular cloning of phogrin, a novel insulin secretory granule membrane protein." Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627383.
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Holroyd, Phillip. "Secretory granule exo-endocytosis studied in the neuroendocrine cell line PC12." Thesis, University of Bath, 2002. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398430.
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Arden, Catherine. "Compartmentation and function of glucokinase in insulin secretory granules." Thesis, University of Newcastle Upon Tyne, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407841.
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Pryde, James Grant. "Biogenesis of secretory granules in the bovine adrenal medulla." Thesis, University of Edinburgh, 1987. http://hdl.handle.net/1842/24238.
Full textBooks on the topic "Secretory granula"
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Bacon, Mark. Como Hacer Marketing Directo: Secretos Para LA Pequena Empresa (Management (Granica)). Ediciones Granica, S.A., 1996.
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Oklopcic, Zoran. Nephos, Scopos, Algorithm. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198799092.003.0005.
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Chapter 5 moves beyond the two most politically consequential understandings of the right to self-determination: attributed to Demos and Ethnos respectively. While normative theorists are not sure how to evoke these figures, this chapter treats them as ensembles that are extracted from Nephos; an even fuzzier and more granular political ‘aerosol’. Against it as a backdrop, the discrete locations of territorial rights will also appear more fuzzified—not as identifiable locations, but rather as Scopos; visual effects of concealed, but nevertheless contestable scopic regimes. Once its holders and objects appear in that light, otherwise incommensurable accounts of the right to self-determination will reveal a denominator they secretly share: a Kelsenian ‘tendency’—an aspiration to increase the degree of constituent attachments across the entirety of the spacetime of a constitutional order whose legitimacy is put in question by a demand for ‘self-determination’.
Book chapters on the topic "Secretory granula"
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Pavelka, Margit, and Jürgen Roth. "Secretory Granules." In Functional Ultrastructure, 86–87. Vienna: Springer Vienna, 2010. http://dx.doi.org/10.1007/978-3-211-99390-3_45.
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Pavelka, Margit, and Jürgen Roth. "Secretory Granule Types." In Functional Ultrastructure, 88–89. Vienna: Springer Vienna, 2010. http://dx.doi.org/10.1007/978-3-211-99390-3_46.
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Tooze, Sharon A. "Maturation of Secretory Granules." In Molecular Mechanisms of Membrane Traffic, 159–62. Berlin, Heidelberg: Springer Berlin Heidelberg, 1993. http://dx.doi.org/10.1007/978-3-662-02928-2_30.
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Fujita, Tsuneo, Tomio Kanno, and Shigeru Kobayashi. "Secretions and Secretory Granules." In The Paraneuron, 13–39. Tokyo: Springer Japan, 1988. http://dx.doi.org/10.1007/978-4-431-68066-6_3.
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Kögel, Tanja, and Hans-Hermann Gerdes. "Maturation of Secretory Granules." In Results and Problems in Cell Differentiation, 137–84. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/400_2009_31.
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Gerasimenko, Oleg. "Ca2+ Measurements in Secretory Granules." In Measuring Calcium and Calmodulin Inside and Outside Cells, 213–29. Berlin, Heidelberg: Springer Berlin Heidelberg, 2001. http://dx.doi.org/10.1007/978-3-642-56851-0_10.
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Hutton, J. C., M. Peshavaria, H. W. Davidson, K. Grimaldi, R. Pogge Von Strandmann, and K. Siddle. "The Insulin Secretory Granule: Features and Functions in Common with Other Endocrine Granules." In Advances in Experimental Medicine and Biology, 385–96. Boston, MA: Springer US, 1986. http://dx.doi.org/10.1007/978-1-4684-5314-0_36.
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Bowman, Grant R., Andrew T. Cowan, and Aaron P. Turkewitz. "Biogenesis of Dense-Core Secretory Granules." In Trafficking Inside Cells, 183–209. New York, NY: Springer New York, 2009. http://dx.doi.org/10.1007/978-0-387-93877-6_10.
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Miwa, I., Y. Toyoda, and S. Yoshie. "Glucokinase in β-Cell Insulin-Secretory Granules." In Frontiers in Diabetes, 350–59. Basel: KARGER, 2004. http://dx.doi.org/10.1159/000079029.
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Guest, Paul C. "Biogenesis of the Insulin Secretory Granule in Health and Disease." In Reviews on Biomarker Studies of Metabolic and Metabolism-Related Disorders, 17–32. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-12668-1_2.
Full textConference papers on the topic "Secretory granula"
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morqenstern, E., and H. Patscheke. "THE SECRETORY PATHWAY IN PLATELETS STUDIED BY CRYO-FIXATION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643491.
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It is widely held, that the constituents packed in the a -granules are released by stimulated platelets via the surface connected system (SCS). By means of the fast-freezing and freeze substitution technique (which allow the investigation of membrane fusion) we found a secretory pathway in platelets (compound exocytosis) without an involvement of the SCS during the release of a-granules. To study the process of a-granule secretion human platelets concentrated in citrated blood plasm were stimulated with thrombin or collagen. 20 - 120 seconds after stimulation the platelets were rapidly frozen with a metal-mirror attachment to the KF 80 cryofixation unit (REICHERT-JUNG). Using plastic spacers droplets of the PRP were slammed against a copper block at 80 K at a rate of 0.2 m/sec. After cryofixation the specimens were transferred (in liquid nitrogen) into a Cs-auto cryosubstitution unit (REICHERT-JUNG). Cryosubstitution was programmed for 48h at 193 K in acetone with 4% osmium tetroxide. The temperature went automatically up to room temperature at a rate of 10 K/h. The specimens were embedded in araldite. The analysis of serial ultrathin sections of platelets in different phases of exocytosis revealed the following. a -granules in apposition showed different stages of swelling and dispersal of their electron dense matrix. Membrane appositions were also found between a -granules. The contraction of a sphere of microfilaments and microtubules during stimulation seemed to support this process. On the other hand this internal contraction prevented most of the a-granules from contacting with the plasmalemma. We observed fusion between swollen -granules in apposition and the plasmalemma and swollen and unswollen a -granules. Thus, large compound granules were formed frequently before fusion of the secretory organelles with the plasmalemma took place. These observations suggested that a -granules in stimulated platelets performed a compound exocytosis after swelling. The process seemed to start with the apposition of a -granule membranes to the plasmalemma. It cannot yet be answered whether the swelling of the granules is due to an osmotically driven influx of water or due to an influx after microfusion.Supported by DFG, Grant Mo 124/2-4
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Koike, Kazuo, and Holm Holmsen. "REQUIREMENT FOR THROMBIN RECEPTOR OCCUPANY DURING PLATELET SECRETION UNDER AGGREGATING CONDITIONS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644469.
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We have previously showed that hirudin abruptly arrests thrombin-induced secretion of acid hydrolase at any stage of its progress, whereas it only affects dense granule secretion only at its initial stages; these results have been interpreted to show that acid hydrolase secretion requires sustained while dense granule secreion ony requires a brief receptor occupancy (Holmsen et al. JBC 256(1981)9393). The requirement for receptor occupancy in thrombin-induced α-granule secretion and secretion during aggregation have been studied. Increasing concentrations of thrombin were added to gel-fitered platelets containing a constant, high concentration of hirudin. Dense granule secretion was initiated at lower thrombin concentration than those required for α-granule secretion and aggregation; acid hydrolase secretion required higher concentrations. A 14-fold exess of hirudin produced abrupt stop of dense granule secretion and α-granule secretion when added to platelets shortly after thrombin; it had no affect after these secretory process had reached 30% of their maximal values. Acid hydrolase secretion was, however, abruptly stopped by hirudin at any stage. When the platelets were allowed to aggregate, all three secretory processes increased their rates and could now be abruptly stopped by hirudin at any stage. Aggregation (optical) occurred slower than dense granule andoαgranule secretion, and was reversed by hirudin when added before it had reached 30% of its maximum. It is concluded thatαgranule secretion, like dense granule secretion, only requires a short receptor occupancy to be completed, in contrast to the requirement for sustained occupancy for hydrolase secretion.α-granule secretion might, however, require longer occupancy than dense granule secretion. It is possible that aggregation potentiates all secretory responses through close cell contact and that the abrupt inhibition by hirudin of all secretions may have been caused by its effect on the slower aggregation.
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Patscheke, H., and G. Mathieu. "MONITORING OF THE PLATELET ALPHA-GRANULE SECRETION IN THE AGGREGOMETER." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643492.
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If platelets are stimulated to secrete and the aggregation is prevented by EDTA and no stirring, the optical density (OD) decreases as a consequence of secretion (Patscheke et al. Thromb. Res. 33: 314, 1984). The purpose of this study was to determine which secretory compartment causes the change in OD and to analyze the quantitative relationship between decrease in OD and granule discharge. Human washed platelets were stimulated with thrombin and A 23187 in a Lumi-Aggregometer (Chrono-Log) which permitted simultaneous recording of the change in OD and of the ATP release from dense granules. At various time intervals, platelet factor 4 (PF-4), [3H)serotonin (5-HT), 8-N-ace-tylglucosaminidase (NAG) and lactate dehydrogenase (LDH) were determined in the supernatant as parameters of the release from the alpha granules, dense granules, lysosomes and the cytoplasm, respectively. In order to prevent the platelet shape change (increase in OD) from interfering with secretion (decrease in OD), the platelets were pretreated with 0.1 nM PAF 2 min prior to the secretagogue. PAF induced the shape change but no release of platelet constituents. The results show that the decrease in OD closely correlates with the release of PF-4. The fractional effects were identical in concentration-effect and time-effect studies. However, neither the decrease in OD nor the release of PF-4 were correlated with the release of ATP and 5-HT from the dense granules or the lysosomal release of NAG. The release of ATP and 5-HT required significantly higher agonist concentrations than the decrease in OD and the release of PF-4 and even higher concentrations were required for the release of NAG. LDH liberation did not exceed 1 % with 1 U/ml thrombin, indicating the absence of lysis. Thrombin 1 U/ml caused a maximum decrease in OD of 11 % and 40 % release of PF-4. In a patient with gray platelet syndrome, the decrease in OD was absent while the release of 5-HT was normal. These results show that the decrease in OD is due to alpha-granule secretion. The turbidimetric method offers a valuable tool for kinetic measurements of alpha-granule secretion. By using a Lumi-Aggregometer, secretion from alpha and dense granules can be monitored simultaneously. (Supported by the Deutsche Forschungsgemeinschaft, Grant Pa-263).
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Malmgren, R. "LUMI-AGGREGOMETER STUDIES OF THE INITIAL ATP-SECRETION FROM COLLAGEN-ADHERENT PLATELETS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643550.
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We have earlier, with the use of a lumi-aggregometer and sub-aggregating doses of collagen (0.2-0.8 ug/ml PRP), been able to detect the initial, aspirin-insensitive secretion of ATP from the collagen-adherent platelets, and to correlate this secretion to the doses of collagen, and onset and degree of subsequent shape change of non-adherent platelets (Malmgren, Thromb Res 4:445, 1986). The present study shows, that 200 ATU of hirudin,which reduced near-maximal aggregation and ATP-secretion induced by high collagen doses (2.5 ug/ml PRP) from 3.35 ± 0.2 uM to 2.85 ± 0.1 uM, did neither reduce the secreted amount of ATP that were 82.5 ± 15 nM in control samples and 90 ± 27.5 nM in hirudin-treated samples, nor reduce platelet shape change when platelets were challenged with 0.31 ug collagen /ml PRP. (200 ATU hirudin completely abolished an equal degree of platelet shape change induced by 0.01 U thrombin). Assuming that 3 % of the platelets in PRP were actually adhering to the collagen fibrils, the secreted amount corresponds to 14.6 ±0.04 pmoles ATP/106adheringplatelets, amounts which closely represented 100 % of their dense granule content. The finding confirms that hirudin does not inhibit platelet adhesion and also indicates, that thrombin-mediated activation of secretory pathways appears not to be involved during the initial phase of platelet-collagen interactions.Dipyridamole (DPA) and dibutyryl cAMP (DBcAMP) inhibited ATP-secretion and platelet aggregation in a dose-dependent manner at high collagen concentrations, but only DBcAMP caused a dose-dependent reduction of ATP secretion (IC50 =10-4 M) induced by sub-aggregating doses of collagen. DPA was devoid of effect in this respect and thus did not inhibit platelet adhesion.Yohimbine, dihydroergotamine and phentolamine reduced ATP-secretion induced by sub-aggregating collagen doses in the mentioned rank order of potency, and with IC50 values in the micromolar range. Ketanserin, ritanserin and propranolol were devoid of effect. The findings suggest that the initial collagen-plate-let interaction involve alfareceptor-mediated mechanisms that may encompass adhesion, while DBcAMP probably interacts with secretory mechanisms connected to phosphatidylinositol turnover.
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Kingston, P. R., K. R. Bruckdorfer, and R. A. Hutton. "AGONIST INDUCED CALCIUM MOBILISATION IN PLATELETS OF PATIENTS WITH "ASPIRIN-LIKE" DEFECTS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644570.
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A group of patients have been described with a condition often referred to as an'Aspirin-like" defect, which is characterised by easy bruising and prolonged bleeding following dental extraction or surgery. Initial studies eliminated a deficiency in coagulation factors, plasma factors, platelet glycoproteins or platelet storage granules as being the cause of this condition and demonstrated a diminished aggregatory and/or secretory response in platelet-rich-plasma to ADP and collagen. Aggregation responses in isolated platelets to thrombin, arachidonic acid and ionomycin are within the normal range, however the response to AD? is dimished. Recent studies have concentrated on the various mechanisms involved in platelet aggregation amongst which is the change in intracellular calcium concentration with accompanied secretion.Using the fluorescent indicator quin2 we have monitored the intracellular calcium changes induced by various agonists in the presence and absence of extracellular calcium in five patients with an "Aspirin-like" defect. In the presence of ImM extracellular calcium, thrombin and ionomycin caused a rapid elevation in intracellular calcium to greater than 1μM within 30 seconds of stimulation. In the absence of extracellular calcium, thrombin and ionomycin caused rises in intracellular calcium of 200nM and 300nM respectively. All the responses observed were within the normal range and indicate that both influx of extracellular calcium and mobilisation of calcium from internal stores has occurred. Therefore the defect that causes this "Aspirin-like" condition is not commonly associated with a defect in calcium mobilisation.
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Blockmans, D., E. Van Houtte, J. Arnout, P. Mombaerts, D. Collen, and J. Vermylen. "TISSUE PLASMINOGEN ACTIVATOR INHIBITS THROMBIN-INDUCED AGGREGATION AND SHAPE CHANGE,BUT FACILITATES SECRETION,IN GEL-FILTERED PLATELETS ONLY." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643763.
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Prolonged administration of tissue plasminogen activator (t-PA) has caused bleeding problems in some patients, that did not necessarily correlate with a significant drop of fibrinogen levels. We have therefore evaluated the effect of t-PA on platelet function in vitro.Incubation of gel-filtered platelets for one hour at 37°C with 180 μg/ml plasminogen and increasing concentrations of t-P(50-1600 ng/ml) significantly inhibited shapechange and aggregation induced by thrombinand the thromboxane mimetic U 46619 in a dose-dependent manner. In an EDTA milieu, whichbolishes aggregation, a dual effect of t-PA and plasminogen was observed in the aggregometer: the thrombin- or U 46619-elicited initial decrease in light transmission, reflectingthe disc-to-sphere transformation of platelets, was almost completely inhibited from 50 ng/ml t-PA upwards; the subsequent increase in light transmission, reflecting granule secretion, was however enhanced by small amounts of t-PA (up to 200 ng/ml). The latter finding was confirmed by direct measurement of secreted ATP:t-PA atconcentrations up to 200ng/ml enhanced thrombin- or U 46619-in-duced secretion. The amount of plasmin generated in the gel-filtered platelets-plasminogen-t-PA mixtures was quantified. The same amountsof plasmin, while also inhibiting the disc-to-sphere transformation of the platelets, did not enhance thrombin-or U 46619-induced ATP secretion. When whole blood or platelet-rich plasma or gel-filtered platelets resuspended in α-antiplas-min-depleted plasma waspreincubated with t-PA, aggregation and/or shape change induced by ristocetin, arachidonic acid, the calcium ionophore A 23187, adenosine diphosphate, U 46619, thrombin, serotonin or platelet activating factor were not modified.Our results suggest that in a purified system the effects of t-PA plus plasminogen onplatelets are distinct from those of plasmin;it appears that low pharmacological concentrations of t-PA enhance the secretory responses to stimuli.
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Kajiwara, Y., M. Sakon, T. Tsujinaka, J. Kambayashi, T. Mori, and T. Murachi. "STUDIES ON ROLE OF CALPAIN IN PLATELET REACTION, UTILIZING NEWLY SYNTHETIZED PEPTIDE ANTAGONISTS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642823.
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The system of calpain (Ca2+-activated protease) and its inhibitor calpastatin in platelets have been well characterized in our laboratory but the role of the system has not been fully elucidated yet, though various endogenous substrates have been identified. Employing SH inhibitors as calpain antagonists, We have proposed a possible role of platelet calpain in myosin light chain (20K) phosphorylation (Biochem.Int. 6,767,1986) but more specific calpain antagonists were required to draw conclusion. Recentry, series of peptide calpain antagonists(PCAs) were syn-thetized such as Ac-Leu-Leu-Nle.al(PCA-I), Ac-Leu-Leu-Met.al(PCA-II) and Leu-Leu-Phe.CH2Cl(PCA-III)(J.Biochem.99,173,1986) and attempts were made to apply them to platelet reaction. ID50 of PCAs against platelet calpain I was as follows; PCA-I:0.04uM,PCA-II:0.luM and PCA-III:0.4uM. Thus, these antagonists were 1000 times more potent than N-ethylmaleimide(NEM), and they did not inhibit Mg2+-ATPase activity of platelet myosin B in contrast to NEM. When PCAs were applied to intact platelets, no effect was obtained against stimulus-linked proteolysis of ABP(aotin binding protein) and P235, indicating poor permeability of the antagonists across the plasma membrane. Thereby PCA was applied to lysed platelets or to permeabilized platelets. Lysed platelets suspension with 2mM EGTA, 2mM EDTA was incubated at 37 C with 32P -ATP,2mM MgCl2, 3mM CaCl2 in the presence or absence of PCA-II and proteolysis of. ABP,P235 and phosphorylation of 20K,47K were studied. The proteolysis and phosphorylation were inhibited by PCA-II in a dose-related manner. Then, PCA-II was applied to permeabilized platelet prepared by a high voltage electric charge to which acriflavine was loaded. PCA-II inhibited Ca2+ stimulated proteolysis and phosphsrylation of the permeabilized platelets likewise but no effect was obtained on Ca2+ stimulated acriflavine secretion from dense granules. These observations indicated that the proteolysis and protein phosphorylation are mediated by calpain but that these phenomena may not be related to secretory process.
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Nachman, R. L., R. L. Silverstein, and A. S. Asch. "THROMBOSPONDIN: CELL BIOLOGY OF AN ADHESIVE GLYCOPROTEIN." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644653.
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Thrombospondin (TSP), a multifunctional 450 KD glycoprotein is a secretory product of thrombin stimulated platelets. It is a major component of the platelets alpha granule constituting approximately 3% of total platelet protein. Thrombospondin does not circulate in appreciable concentrations ∽0 100 ng/ml); however, the tissue distribution is broad. In addition to its expression on the membrane of activated platelets, the protein is synthesized by fibroblasts endothelial cells, glial cell smooth muscle cells alveolar pneumocytes mononuclear phagocytes and various tumor cells. TSP is a major constituent of the extracellular matrix and has been demonstrated in the vessel wall, basement membrane and glandular connective tissue. Fibroblasts, smooth muscle cells and endothelial cells in tissue culture incorporate TSP into the extracellular matrix. Matrix TSP is under cell-cycle regulatory control. Mesenchymal cells in the proliferative phase synthesize greater amounts of TSP than non growing cells. Platelet derived growth factor induces smooth muscle cell and glial cell synthesis of TSP. Atheromatous lesions contain increased amounts of TSP compared to normal vessels emphasizing the potential role of TSP in the interaction of proliferating cells with the matrix. TSP binds specifically, saturably, and reversibly to mouse peritoneal macrophages and to cells of the monocyte-like human cell line U937. Binding was time dependent and was optimal in the presence of both Ca++ and Mg++. PMA stimulated U937 cells and activated macrophages bound TSP to an equivalent extent as resting cells. The TSP binding site on the surface of U937 cells and peripheral blood monocytes mediates the adhesive interaction between these cells and thrombin-stimulated platelets. Using a sensitive rosetting assay we found that monocytes were not rosetted by resting platelets while >90% were rosetted by thrombin-stimulated platelets. Monoclonal and polyclonal anti-TSP antibodies markedly inhibited rosetting as did TSP itself. Antifibronectin or non-immune control antibodies did not inhibit rosetting, nor did fibronectin, fibrinogen, the fibronectinadhesion tetrapeptide arg-gly-asp-ser (RGDS), or heparin. The TSP membrane receptor, an 88 KD glycoprotein, formely known as GPIV has been identified in platelets, endothelial cells, monocytes and a variety of tumor cells. TSP may thus serve as a molecular bridge linking activated platelets with monocytes at sites of early vascular injury. Such interactions involving the TSP receptor complex may be of critical importance in the regulation of thrombosis and the initiation of atherosclerosis.
Reports on the topic "Secretory granula"
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Bonilla-Mejía, Leonardo, and Erika Londoño-Ortega. Geographic Isolation and Learning in Rural Schools. Banco de la República, August 2021. http://dx.doi.org/10.32468/be.1169.
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Rural schools are usually behind in terms of learning, and part of this could be related to geographical isolation. We explore this hypothesis, assessing the effect of distance between rural schools and local governments on learning in Colombia. We use spatial discontinuous regression models based on detailed administrative records from the education system and granular geographic information. Results indicate that distance to towns and Secretary of Education has significant negative effects on students’ standardized test scores. We evaluated alternative mechanisms, finding that the effect of distance is partly explained by differences in critical educational inputs, such as teachers’ education attainment and contract stability. Finally, we assess the mediating role of a program providing monetary incentives to teachers and principals in remote areas.