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PubMed1993

Hepatic tyrosine-phosphorylated proteins identified and localized following in vivo inhibition of protein tyrosine phosphatases: effects of H2O2 and vanadate administration into rat livers.

Injection of a combination of H2O2 and vanadate (H/V) into the portal vein of rat livers resulted in inhibition of protein tyrosine phosphatase activity and led to a dramatic enhanced in vivo protein tyrosine phosphorylation. Some of the phosphorylated proteins were identified as the beta-subunit of the insulin receptor, the insulin receptor substrate 1 (pp185), PLC-gamma (pp145), and a 100 kDa PLC-gamma-associated protein. Immunofluorescense and immune electron microscopy of frozen liver sections with anti-P-Tyr antibodies revealed that most of the tyrosine-phosphorylated proteins are localized in close proximity to the plasma membrane in intercellular adherence junctions and tight junction regions. This close in vivo association between membranal protein tyrosine kinases, their target proteins, and cytoskeletal elements could enable formation of 'signaling complexes' which may play a role in transmembrane signal transduction. By affinity chromatography over immobilized anti-P-Tyr antibodies, a large number of these tyrosine-phosphorylated proteins were partially purified.

Animals↗
PubMed1994

Scar formation in the vestibular sensory epithelium after aminoglycoside toxicity.

Hair cell degeneration and the repair process due to differing types of trauma have been studied extensively in the organ of Corti. It has been determined that, during scar formation, after differing types of trauma to the auditory sensory system, the reticular lamina is maintained with adherens junctions and tight junctions. We investigated the repair process within the vestibular epithelium. Hair cell degeneration was induced by the unilateral application of streptomycin to the inner ears of guinea pigs. Whole mount preparations of all five vestibular organs were processed and examined by fluorescence, light and electron microscopy. Scar formation was seen as early as 4 days post-treatment with streptomycin and was noted to coincide with hair cell degeneration. Neighboring supporting cells swelled and filled the space beneath the degenerating hair cell. Between three and five supporting cells participate in the reparative process. The distribution of cytokeratin is also altered during scar formation. The area once occupied by the hair cell becomes filled with cytokeratin-rich processes of supporting cells. It appears that differing numbers of supporting cells are involved in the reparative process within the vestibular sensory epithelium as compared to the auditory system. The reticular lamina remains intact at all times. This may possibly prevent mixing of fluids between different compartments in the inner ear and dysfunction of the vestibular sensory organs.

Actins↗
PubMed2000

Inflammatory mediators and modulation of blood-brain barrier permeability.

1. Unlike some interfaces between the blood and the nervous system (e.g., nerve perineurium), the brain endothelium forming the blood-brain barrier can be modulated by a range of inflammatory mediators. The mechanisms underlying this modulation are reviewed, and the implications for therapy of the brain discussed. 2. Methods for measuring blood-brain barrier permeability in situ include the use of radiolabeled tracers in parenchymal vessels and measurements of transendothelial resistance and rate of loss of fluorescent dye in single pial microvessels. In vitro studies on culture models provide details of the signal transduction mechanisms involved. 3. Routes for penetration of polar solutes across the brain endothelium include the paracellular tight junctional pathway (usually very tight) and vesicular mechanisms. Inflammatory mediators have been reported to influence both pathways, but the clearest evidence is for modulation of tight junctions. 4. In addition to the brain endothelium, cell types involved in inflammatory reactions include several closely associated cells including pericytes, astrocytes, smooth muscle, microglia, mast cells, and neurons. In situ it is often difficult to identify the site of action of a vasoactive agent. In vitro models of brain endothelium are experimentally simpler but may also lack important features generated in situ by cell:cell interaction (e.g. induction, signaling). 5. Many inflammatory agents increase both endothelial permeability and vessel diameter, together contributing to significant leak across the blood-brain barrier and cerebral edema. This review concentrates on changes in endothelial permeability by focusing on studies in which changes in vessel diameter are minimized. 6. Bradykinin (Bk) increases blood-brain barrier permeability by acting on B2 receptors. The downstream events reported include elevation of [Ca2+]i, activation of phospholipase A2, release of arachidonic acid, and production of free radicals, with evidence that IL-1 beta potentiates the actions of Bk in ischemia. 7. Serotonin (5HT) has been reported to increase blood-brain barrier permeability in some but not all studies. Where barrier opening was seen, there was evidence for activation of 5-HT2 receptors and a calcium-dependent permeability increase. 8. Histamine is one of the few central nervous system neurotransmitters found to cause consistent blood-brain barrier opening. The earlier literature was unclear, but studies of pial vessels and cultured endothelium reveal increased permeability mediated by H2 receptors and elevation of [Ca2+]i and an H1 receptor-mediated reduction in permeability coupled to an elevation of cAMP. 9. Brain endothelial cells express nucleotide receptors for ATP, UTP, and ADP, with activation causing increased blood-brain barrier permeability. The effects are mediated predominantly via a P2U (P2Y2) G-protein-coupled receptor causing an elevation of [Ca2+]i; a P2Y1 receptor acting via inhibition of adenyl cyclase has been reported in some in vitro preparations. 10. Arachidonic acid is elevated in some neural pathologies and causes gross opening of the blood-brain barrier to large molecules including proteins. There is evidence that arachidonic acid acts via generation of free radicals in the course of its metabolism by cyclooxygenase and lipoxygenase pathways. 11. The mechanisms described reveal a range of interrelated pathways by which influences from the brain side or the blood side can modulate blood-brain barrier permeability. Knowledge of the mechanisms is already being exploited for deliberate opening of the blood-brain barrier for drug delivery to the brain, and the pathways capable of reducing permeability hold promise for therapeutic treatment of inflammation and cerebral edema.

Animals↗
PubMed2000

Electron microscopic contrast of the cytoskeleton and junctional complexes of intestinal epithelial cells by ethanolic phosphotungstic acid.

After glutaraldehyde fixation and treatment with ethanolic phosphotungstic acid (E-PTA) before plastic embedding, sections of rat large intestine showed a characteristic electron contrasting pattern in epithelial cells. The axis of microvilli, terminal web, a thin band below the luminal plasma membrane, centrioles and junctional complexes (tight junctions, adherens junctions, and desmosomes) appeared highly contrasted. In addition to protein components of microfilaments and intermediate filaments, proteins from the junctional complexes could also be implicated in the contrasting reaction with E-PTA. Mitochondrial membranes, chromatin masses, and nucleoli of enterocytes showed considerable electron density, whereas no reaction was found in the glycocalyx and mucin content of goblet cells. The clear visualization of cytoskeleton elements and junctional complexes by E-PTA contrasting represents a simple and valuable method for studies on the normal and pathological organization of these structures in epithelial cells.

Animals↗
PubMed1969

The histogenesis of rat intercostal muscle.

Intercostal muscle from fetal and newborn rats was examined with the electron microscope. At 16 days' gestation, the developing muscle was composed of primary generations of myotubes, many of which were clustered together in groups. Within these groups, the membranes of neighboring myotubes were interconnected by specialized junctions, including tight junctions. Morphologically undifferentiated cells surrounded the muscle groups, frequently extended pseudopodia along the interspace between adjacent myotubes, and appeared to separate neighboring myotubes from one another. At 18 and 20 days' gestation, the muscle was also composed of groups of cells but the structure of the groups differed from that of the groups observed at 16 days. Single, well differentiated myotubes containing much central glycogen and peripheral myofibrils dominated each group. These large cells were interpreted as primary myotubes. Small, less differentiated muscle cells and undifferentiated cells clustered around their walls. Each cluster was ensheated by a basal lamina. The small cells were interpreted as primordia of new generations of muscle cells which differentiated by appositional growth along the walls of the large primary myotubes. All generations of rat intercostal muscle cells matured to myofibers between 20 days' gestation and birth. Coincidentally, large and small myofibers diverged from each other, leading to disintegration of the groups of muscle cells. Undifferentiated cells frequently occurred in the interspaces between neighboring muscle cells at the time of separation. Myofibers arising at different stages of muscle histogenesis intermingled in a checkerboard fashion as a result of this asynchronous mode of development. The possibility of fusion between neighboring muscle cells in this developing system is discussed.

Animals↗
PubMed2004

Adaptors, junction dynamics, and spermatogenesis.

Adaptors are component proteins of junctional complexes in all epithelia, including the seminiferous epithelium of the mammalian testis. They recruit other regulatory and structural proteins to the site of both anchoring junctions (such as cell-cell actin-based adherens junctions [AJs], e.g., ectoplasmic specialization [ES] and tubulobulbar complex, which are both testis-specific cell-cell actin-based AJ types, and cell-cell intermediate filament-based desmosome-like junctions) and tight junctions (TJ). Furthermore, adaptors per se can be substrates and/or activators of kinases or phosphatases. As such, the integrity of cell junctions and the regulation of junction dynamics during spermatogenesis rely on adaptors for their ability to recruit and link different junctional components to the same site and to tether transmembrane proteins at both anchoring and TJ sites to the underlying cytoskeletons, such as the actin filaments, intermediate filaments, and microtubules. These protein-protein interactions are possible because adaptors are composed of conserved protein binding domains, which allow them to link to more than one structural or signaling protein, recruiting multi-protein complexes to the same site. Herein, we provide a timely review of adaptors recently found at the sites of AJ (e.g., ES) and TJ. In addition, several in vivo models that can be used to delineate the function of adaptors in the testis are described, and the role of adaptors in regulating junction dynamics pertinent to spermatogenesis is discussed.

Adaptor Proteins, Signal Transducing↗
PubMed1985

The effects of thermal stimulation on the ultrastructure of the human atrichial sweat gland. II. The duct.

The duct of the human atrichial sweat gland, after thermal stimulation, exhibited increased cytoplasmic vesiculation, particularly of the luminal cells, a widening of the intercellular spaces, and the presence of particulate matter in the lumen. The luminal cells of the coiled zone also displayed varying degrees of apical disruption, most probably due to filtration of cell fluid through the terminal web of microfilaments. This zone seems to have a secretory as well as an absorptive role. Specialized junctions (intercellular bridges, gap junctions and tight junctions) were found amongst the basal and luminal cells of the wall of the ascending duct.

Cytoplasm↗
PubMed1977

Intercellular spaces and cell junctions in endometrial glands: their possible role in menstruation.

Intercellular spaces and cell junctions in human endometrial glands were studied by elctron microscopy following different methods of fixation. The size of the spaces, known to alter during the cycle, was found to depend also on the method of fixation. Various intrusive cells and different types of cell debris were seen in these spaces. The three most widely recognized cell junctions (desmosomes, tight junctions and gap junctions), were all most abundant near the cell apices. The possible significance of these findings in elucidating the cellular mechanism of menstruation is discussed.

Endometrium↗
PubMed2001

Cytoskeletal regulation of pulmonary vascular permeability.

The endothelial cell (EC) lining of the pulmonary vasculature forms a semipermeable barrier between the blood and the interstitium of the lung. Disruption of this barrier occurs during inflammatory disease states such as acute lung injury and acute respiratory distress syndrome and results in the movement of fluid and macromolecules into the interstitium and pulmonary air spaces. These processes significantly contribute to the high morbidity and mortality of patients afflicted with acute lung injury. The critical importance of pulmonary vascular barrier function is shown by the balance between competing EC contractile forces, which generate centripetal tension, and adhesive cell-cell and cell-matrix tethering forces, which regulate cell shape. Both competing forces in this model are intimately linked through the endothelial cytoskeleton, a complex network of actin microfilaments, microtubules, and intermediate filaments, which combine to regulate shape change and transduce signals within and between EC. A key EC contractile event in several models of agonist-induced barrier dysfunction is the phosphorylation of regulatory myosin light chains catalyzed by Ca(2+)/calmodulin-dependent myosin light chain kinase and/or through the activity of the Rho/Rho kinase pathway. Intercellular contacts along the endothelial monolayer consist primarily of two types of complexes (adherens junctions and tight junctions), which link to the actin cytoskeleton to provide both mechanical stability and transduction of extracellular signals into the cell. Focal adhesions provide additional adhesive forces in barrier regulation by forming a critical bridge for bidirectional signal transduction between the actin cytoskeleton and the cell-matrix interface. Increasingly, the effects of mechanical forces such as shear stress and ventilator-induced stretch on EC barrier function are being recognized. The critical role of the endothelial cytoskeleton in integrating these multiple aspects of pulmonary vascular permeability provides a fertile area for the development of clinically important barrier-modulating therapies.

Animals↗
PubMed2002

Junctional adhesion molecules and interendothelial junctions.

Similar to epithelia, endothelial cells are linked to each other via intercellular junctional complexes including gap junctions, adherens junctions and tight junctions. While polarized epithelial cells show a high degree of spatial sorting of junctional complexes, endothelia organize their junctions randomly. For this reason the nature of endothelial contacts may be highly adaptable to the need of permeability and leukocyte transmigration. For instance, high endothelial venules (HEVs) in lymphoid organs, where lymphocytes continuously exit the bloodstream, generally show more leaky contacts than brain with its impermeable blood-brain barrier. We recently identified an Ig superfamily molecule named JAM-2 which is specifically expressed in junctions of lymphatic endothelial cells and HEVs. We showed that JAM-2 belongs to the novel CTX molecular family and we now cloned the human equivalent of JAM-2. The presence of JAM-2 at sites of constitutive lymphocyte circulation argues for a role of this molecule in facilitating transmigration. This is supported by the increased transmigration in vitro across endothelial cells overexpressing JAM-2 at intercellular contacts.

Amino Acid Sequence↗
PubMed2004

Blood-testis barrier dynamics are regulated by {alpha}2-macroglobulin via the c-Jun N-terminal protein kinase pathway.

The blood-testis barrier (BTB), in contrast to the blood-brain and blood-retina barriers, is composed of coexisting tight junctions, gap junctions, and basal ectoplasmic specializations, a testis-specific type of adherens junction. Recent studies showed that BTB restructuring that facilitates germ cell migration during spermatogenesis involves proteolysis, an event that is usually restricted to the cell-matrix interface in other epithelia. For instance, a surge in alpha(2)-macroglobulin (alpha(2)-MG), a protease inhibitor produced by Sertoli cells, was detected at the Sertoli-Sertoli and Sertoli-germ cell interface in the epithelium during cadmium chloride-induced BTB disruption in adult rats. It is thus proposed that the increase in alpha(2)-MG is crucial for protecting the epithelium from unwanted proteolysis as well as regulating the availability of cytokines that affect junction turnover. Although both tight junction and adherens junction dynamics at the BTB are regulated via the p38 MAPK signaling pathway, the mechanism(s) that regulates alpha(2)-MG is entirely unknown. In this study, we have shown that by administering dimethylaminopurine, a c-Jun N-terminal protein kinase (JNK) inhibitor, to the testis, JNK activity was blocked specifically and alpha(2)-MG production was inhibited, worsening the cadmium chloride-induced damage to the epithelium. Studies coupled with inhibitors, immunoblottings, and immunofluorescent and electron microscopy have unequivocally demonstrated that the JNK signaling pathway is a putative regulatory pathway for alpha(2)-MG production in the testis. This finding illustrates for the first time that a cell-matrix restructuring event occurs in normal cell physiology at the cell-cell interface in the testis, highlighting the significance of alpha(2)-MG in the regulation of BTB function.

Adenine↗
PubMedDate not supplied

Isolation and characterization of a bovine visceral endoderm cell line derived from a parthenogenetic blastocyst.

A cell line, BPE-1, was derived from a parthenogenetic 8-d in vitro-produced bovine blastocyst that produced a cell outgrowth on STO feeder cells. The BPE-1 cells resembled visceral endoderm previously cultured from blastocysts produced by in vitro fertilization (IVF). Analysis of the BPE-1 cells demonstrated that they produced serum proteins and were negative for interferon-tau production (a marker of trophectoderm). Transmission electron microscopy revealed that the cells were a polarized epithelium connected by complex junctions resembling tight junctions in conjunction with desmosomes. Rough endoplasmic reticulum was prominent within the cells as were lipid vacuoles. Immunocytochemistry indicated the BPE-1 cells had robust microtubule networks. These cells have been grown for over 2 yr for multiple passages at 1:10 or 1:20 split ratios on STO feeder cells. The BPE-1 cell line presumably arose from embryonic cells that became diploid soon after parthenogenetic activation and development of the early embryo. However, metaphase spreads prepared at passage 41 indicated that the cell population had a hypodiploid (2n = 60) unimodal chromosome content with a mode of 53 and a median and mean of 52. The cell line will be of interest for functional comparisons with bovine endoderm cell lines derived from IVF and nuclear transfer embryos.

Animals↗
PubMed1997

Histological study of the seminiferous epithelium in the Japanese rat snake, Elaphe climacophora: identification of spermatogonium.

To clarify the features of the seminiferous epithelium of the Japanese rat snake, Elaphe climacophora, the identification of spermatogonium and the examination of features of cell to cell junctions were performed in the present study. As for the identification, 5-bromo-2-deoxyuridine (BrdU) incorporation was examined immunohistochemically to mark spermatogonia. The seminiferous epithelium was observed throughout a year at the electron microscopic level. BrdU immunoreactivity was detected not only in the cells of the first layer of the seminiferous epithelium but also in the second and/or third layers. The cells immunoreactive in the first layer did not seem to attach to the basement membrane and were recognized throughout a year. To investigate cell to cell junctions, we performed actin filament detection by phalloidin staining. Distribution of actin filaments was different from that in mammalian species. At the ultrastructural level, Sertoli-Sertoli cell junctions were observed. Sertoli cells formed junctional complexes. Tight junctions were clearly found, but lacked the backing by actin filaments. These results indicate that the blood-testis barrier of the Japanese rat snake was structurally different from that of mammalian species. In conclusion, the seminiferous epithelium of the Japanese rat snake is intermediate in morphology between amphibians and mammals.

Actins↗
PubMedDate not supplied

Synovial sarcoma: a review and update, with emphasis on the ultrastructural characterization of the nonglandular component.

Classic biphasic synovial sarcoma is usually not a problem in identification, whereas the monophasic spindle cell form continues to be a challenge in the differential diagnosis of spindle cell neoplasms. Most synovial sarcomas do not arise from a joint or tendon sheath, and by electron microscopy and immunohistochemistry they differ in several ways from nonneoplastic synovium. The cell of origin of synovial sarcoma is unknown, but certain features are rather consistently observed in the biphasic tumors and are useful in identifying monophasic samples. These features are apparent by immunohistochemistry and electron microscopy, both of which indicate early epithelial differentiation in the nonglandular component of the neoplasm. With immunohistochemistry, some of these cells stain for keratin. By electron microscopy, a gradient of differentiation from unclassifiable spindle cells to fully differentiated epithelial lining cells is demonstrable. A review and illustration of the ultrastructural characteristics in this spectrum of intermediate cells constitute the main emphasis of the article. The cells tend to be oval and polygonal; to be arranged in clusters surrounded by basal lamina or flocculent matrix; to have junctions, including tight junctions, and to form villuslike filopodia, true microvilli, canaliculi, and microlumina. This range of ultrastructural features is usually diagnostic of the nonglandular phase of synovial sarcoma.

Adolescent↗
PubMed1982

The use of lanthanum chloride as a marker for intercellular junctions in rat exocrine pancreas.

A simple technique of perfusion and immersion of tissue in fixative containing lanthanum chloride as an extracellular tracer is described. In addition to functioning as a tracer, the lanthanum chloride appears to enhance electron staining. In rat exocrine pancreas, intercellular spaces between exocrine and centroductular cells were outlined clearly be electron dense material and, at cellular interfaces, spot desmosomes, gap junctions, and tight junctions were demonstrated. The technique proved simple and effective and should prove useful in studies of epithelial and other tissues.

Animals↗
PubMed1991

Intercellular junctions and tumor behavior in lung cancer.

We examined the ultrastructure of 76 lung cancers and counted the number of intercellular junctions per area of tissue section. The total number of desmosomes, intermediate junctions, and tight junctions ranged from zero to 300 per 0.157 cm2 of tissue section area, and each type of carcinoma showed a considerable range in concentration of intercellular junctions. Multivariate analysis showed that the number of junctions was significantly tied to the probability of the patient's having extensive stage and to survival time, even after accounting for the routine light microscopic diagnosis of small cell versus non-small cell carcinoma. These results suggest that a tumor's ability to spread and metastasize is inversely related to its number of intercellular junctions, and this conclusion appears to apply to both small cell and non-small cell carcinomas.

Adenocarcinoma↗
PubMed1989

Membrane specializations in the satellite cells of the chicken ciliary ganglion.

Ciliary ganglia of 8 to 19 days in ovo and 1 to 10 days posthatched chickens have been investigated with the freeze-fracture technique. The satellite cell membrane contained at all ages specific small intramembrane particles about 6-7 nm in size and arranged in an orthogonal order (OAPs). Along with these specialized particles, gap junctions and tight junctional strands were found between adjacent satellite cells.

Animals↗
PubMed1987

The ultrastructure of membranes in sympathetic ganglia.

This review presents some recent observations made on membranes in the mammalian sympathetic ganglia after application of freeze-fracturing and histochemistry. After freeze-fracture clear differences have been found between the neuronal and the satellite cell plasmalemma. The satellite cell plasma membrane exhibits specialized intramembrane particles not found in the neuronal membrane. Freeze-fracture cytochemistry reveals a further difference between the neurons and satellite cells i.e., a higher density of beta-hydroxysterols is present in the satellite cell membrane than in the neuronal membrane. Histochemical methods to localize 5'-nucleotidase, Ca2+-ATPase and Na+/K+-ATPase in the membranes have been utilized. The cytochemical reaction products of 5'-nucleotidase and Ca2+-ATPase were found on the external aspect of the plasma membranes. The Na+/K+-ATPase reaction product was located on the cytoplasmic aspect of the membranes, with most activity seen in the satellite cell membrane. With respect to the intercellular junctions, the presynaptic membranes have been analyzed with the freeze-fracture technique under stimulated and unstimulated conditions and ultrastructural differences have been observed which might be correlated to neurotransmission. Furthermore, gap junctions and tight junctional elements occur between the satellite cells surrounding the neuronal perikarya and their processes.

5'-Nucleotidase↗