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At least 19 recordsLinked to original sources
PubMed1988

An electron microscope study of the development of the exocrine and endocrine pancreas with special reference to intercellular junctions.

Intercellular junctions in pancreatic acinar, duct and endocrine cells were studied by thin section and freeze-fracture methods in developing rats and mice. Undifferentiated cells were joined by the zonula occludens and isolated fragments of tight junctional strands. Small gap junctions were either occasionally associated with tight junctional strands or appeared independent of them. During the morphological differentiation of acinar cells, strands of the zonula occludens developed to form a complicated meshwork while gap junctions rapidly increased in size. Duct cells were joined by the less-developed zonula occludens but gap junctions were rarely seen. In the neonate, intercellular junctions were similar to those in adult acini and intercalated ducts. Endocrine cells were joined by maculae occludentes and small gap junctions. During late prenatal days, the macula occludens increased in size and gap junctions in number. Sometimes tight junctional strands disappeared to leave membrane elevations, some of which were associated with small gap junctions. Maculae occludentes on endocrine cells were gradually fragmentized and diminished during postnatal development. They were completely lost in the rat. These results suggest that intercellular junctions play important roles in pancreatic development. In particular, the transient development of maculae occludentes is associated with endocrine cell development, and intercellular communication mediated by gap junctions may be important for the differentiation of acinar and endocrine cells.

Animals↗
PubMed2000

Melatonin effects on intercellular junctional communication in MCF-7 human breast cancer cells.

Melatonin exerts a direct antiproliferative effect on estrogen-responsive MCF-7 cells in culture. Recently, the importance of the anti-invasive actions of melatonin as a part of the oncostatic action of this indolamine has been reported. Gap junctional intercellular communication is known to be involved in controlling cell proliferation and differentiation, and a decrease in intercellular junctional communication has been described in highly invasive mammary cancer cells. Because melatonin at physiological doses (1 nM) shifts MCF-7 cells to a lower invasive status, we postulate that melatonin could modulate the levels of gap junctional intercellular communication in these tumor cells. To test our hypothesis, we studied gap junctional intercellular communication in MCF-7 human breast cancer cells previously (7-8 days) treated, or not, with melatonin (10 microM or 1 nM). Using the scrape-loading assay dye-transfer technique to introduce 0.05% Lucifer yellow into cells, we measured the ability of the tumor cells to transfer dye to adjacent cells. Rhodamine dextran (0.05%) was used as a control dye to verify that dye-transfer occurs through intercellular junctions. The presence of melatonin (10 microM or 1 nM) in the culture medium significantly increased (P < 0.01) the transfer of the dye to adjacent cells through gap junctions. This increase was greater at 10 microM melatonin, and averaged scan profiles of cells treated with melatonin 10 microM showed a statistically significant increase (P < 0.01) in the integrated optical density values, and a broadening of the densitometric scan. These findings suggest that melatonin could exert its antitumor action, at least in part, by increasing regulatory signals that are passed between adjacent epithelial cells through intercellular junctions.

Breast Neoplasms↗
PubMed1997

Elimination of intercellular junctional communication requires lower Ras(leu61) levels than stimulation of anchorage-independent proliferation.

One of the effects of transformation by a variety of factors is a decrease in gap junctional, intercellular communication (GJIC). To investigate the role of the Ras oncogene product in gap junction closure, and to incorporate GJIC into the gamut of transformation-related properties which can be regulated by increasing levels of oncogene expression, a panel of murine C3H10T1/2 and 3T3L1 fibroblasts was constructed in which graded increments of Ras(leu61) could reliably be obtained. The inducibly activated Ras(leu61) protein substantially reduced or eliminated GJIC at levels much lower than those needed for neoplastic transformation, as indicated by acquisition of the ability to proliferate in the absence of anchorage. These results indicate that disruption of GJIC, although necessary, is not sufficient for neoplastic transformation in this system.

3T3 Cells↗
PubMed1998

VE-cadherin and desmoplakin are assembled into dermal microvascular endothelial intercellular junctions: a pivotal role for plakoglobin in the recruitment of desmoplakin to intercellular junctions.

Vascular endothelial cells assemble adhesive intercellular junctions comprising a unique cadherin, VE-cadherin, which is coupled to the actin cytoskeleton through cytoplasmic interactions with plakoglobin, beta-catenin and alpha -catenin. However, the potential linkage between VE-cadherin and the vimentin intermediate filament cytoskeleton is not well characterized. Recent evidence indicates that lymphatic and vascular endothelial cells express desmoplakin, a cytoplasmic desmosomal protein that attaches intermediate filaments to the plasma membrane in epithelial cells. In the present study, desmoplakin was localized to intercellular junctions in human dermal microvascular endothelial cells. To determine if VE-cadherin could associate with desmoplakin, VE-cadherin, plakoglobin, and a desmoplakin amino-terminal polypeptide (DP-NTP) were co-expressed in L-cell fibroblasts. In the presence of VE-cadherin, both plakoglobin and DP-NTP were recruited to cell-cell borders. Interestingly, beta-catenin could not substitute for plakoglobin in the recruitment of DP-NTP to cell borders, and DP-NTP bound to plakoglobin but not beta-catenin in the yeast two-hybrid system. In addition, DP-NTP colocalized at cell-cell borders with alpha-catenin in the L-cell lines, and endogenous desmoplakin and alpha-catenin colocalized in cultured dermal microvascular endothelial cells. This is in striking contrast to epithelial cells, where desmoplakin and alpha -+catenin are restricted to desmosomes and adherens junctions, respectively. These results suggest that endothelial cells assemble unique junctional complexes that couple VE-cadherin to both the actin and intermediate filament cytoskeleton.

Animals↗
PubMed1994

A novel technique for the study of intercellular, junctional communication: electroporation of adherent cells on a partly conductive slide.

One of the effects of neoplastic transformation by a variety of factors is a decrease in gap junctional, intercellular communication (GJIC). The investigation of junctional permeability is usually conducted through the microinjection of the fluorescent dye, Lucifer yellow, followed by observation of its migration into neighboring cells. This is a time-consuming approach, requiring expensive equipment. To overcome these problems, a novel technique was devised which takes advantage of the ability of short electric pulses to create transient "pores" on the cell membrane through which Lucifer yellow can enter, simultaneously and into large numbers of cells, with minimal disturbance to cellular metabolism. Cells were grown on a glass slide, half of which was coated with electrically conductive, optically transparent, indium-tin oxide. An electric pulse was applied in the presence of Lucifer yellow, causing its penetration into the cells growing on the conductive half of the slide, and the migration of the dye to the nonelectroporated cells growing on the nonconductive area was microscopically observed under fluorescence illumination. Using this technique, we investigated the relationship between expression of the middle tumor antigen of polyoma virus (mT) and GJIC in two representative cell systems with different responses to mT. The results show that low mT expression levels, although unable to transform rat F111 cells fully, are able to interrupt GJIC. Although parts of this mechanism might be mediated through protein kinase C (PKC), mT appears to have additional functions. PKC, however, had the opposite effect upon junctional permeability in a clone of mouse NIH-3T3 fibroblasts; intercellular communication in these cells appears to require PKC activity.

3T3 Cells↗
PubMed1996

Induction of gap junctional intercellular communication by vitamin D in human skin fibroblasts is dependent on the nuclear Induction of gap junctional intercellular communication by vitamin D in human skin fibroblasts is dependent on the nuclear vitamin D receptor.

The physiologically active metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D3 (calcitriol), induces gap junctional intercellular communication in human skin fibroblasts 161BR at a concentration of 10(-7) M. In human skin fibroblasts, FIB5, devoid of a functional nuclear vitamin D receptor (VDR), there is no effect on gap junctional intercellular communication. Parallel to the increase in cell-cell communication, we observed a VDR-dependent increase in connexin43 protein and connexin43 mRNA levels. These results suggest that 1alpha,25-dihydroxyvitamin D3 affects gap junctional intercellular communication at the level of transcription or of mRNA stability via the nuclear VDR.

Calcitriol↗
PubMedDate not supplied

Birbeck granules or Birbeck junctions? Intercellular "zipperlike" lattice junctions in eosinophilic granuloma of bone.

Three cases of eosinophilic granuloma of bone exhibited intercellular attachments between histiocytes, with a pentalaminar structure identical to that seen in nearby intracellular Birbeck granules (BG). It is proposed that the term "lattice junction" be coined to describe this organelle, which seems to be expressed only by cells of monocytic-histiocytic lineage. While this finding confirms the ability of the surface membrane to form such structures, it does not necessarily preclude other intracytoplasmic sites of origin for some BG. The previously suggested role of BG in membrane storage and regulation is reiterated as a supportable model for their function.

Adolescent↗
PubMed1990

Comparative effects of phenobarbital, DDT, and lindane on mouse hepatocyte gap junctional intercellular communication.

Gap junctional intercellular communication appears to be important in the regulation of cellular homeostasis, differentiated cell functions, and growth control in adult tissues. Interruption of intercellular communication by chemical compounds has been shown to be a sublethal response to a number of tumor promoters. The mechanism by which tumor promoters inhibit intercellular communication remains unresolved. In the present study the kinetics of inhibition of mouse hepatocyte gap junctional intercellular communication (measured by dye coupling) by three well-established hepatic tumor promoters [phenobarbital, 1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane (DDT), and gamma-hexachlorocyclohexane (lindane)] are compared. All three compounds inhibited intercellular communication in a time- and dose-dependent manner in both freshly plated and 24-hr-old hepatocyte cultures. Following removal of the tumor promoters from the culture medium, intercellular communication was reestablished within 0.5 hr (phenobarbital) to 1.5 hr (DDT and lindane). Prolonged treatment of hepatocytes for up to 48 hr with the three promoters resulted in the continued inhibition of intercellular communication by lindane and DDT, but the development of refractoriness to phenobarbital-induced inhibition of intercellular communication. Concomitant treatment with combinations of the three promoters showed an additive effect of the compounds on inhibition of intercellular communication. Inhibition of intercellular communication by phenobarbital was prevented by addition of the cytochrome P450 enzyme inhibitor SKF-525A. SKF-525A had no effect on the inhibition of intercellular communication induced by lindane or DDT. Coincubation of the three promoters with the cAMP analog 8-bromo-cAMP prevented the promoter-induced inhibition of intercellular communication.

Animals↗
PubMed1998

[Effect of d-limonene, Salvia miltiorrhiza and turmeric derivatives on membrane association of Ras gene product and gap junction intercellular communication].

Gap junction intercellular communication (GJIC), H-ras oncogene expression and Ras oncogene product(P21ras protein) expression were studied in four human solid tumor cell lines, W1-38, CACO2, A549 and PaCa (with the different Ras gene mutation rate), and the effects of four compounds, Salvia miltiorrhiza derivative (SMD), d-limonene, turmeric derivative I(TD-I) and turmeric derivative II(TD-II), on them. The abilities of the four solid tumor cell lines to transfer dye to adjacent cells were examined using the scrape-loading/dye transfer technique, and the H-ras oncogene expression by Northern blotting and P21ras protein expression by Western blotting. The results showed the loss of intercellular coupling in PaCa cells, slight GJIC in A549 and CACO2 cells, and good GJIC in W1-38 cells. The four compounds used was shown to improve the GJIC of PaCa to different extents. The amount of total and membrane associated P21ras in PaCa cells were decreased after treatment with SMD, d-limonene and TD-I(2.5 micrograms.ml-1) for 48 h. Concomitantly, the growth of PaCa cells decreased in soft agar and GJIC was enhanced. The relative potency was found to be: d-limonene > SMD > TD-I = TD-II. No significant effect of the four compounds on H-ras oncogene expression was observed. These results suggest that 1. there was an excellent correlation between loss of Lucifer Yellow dye transfer and ras gene mutation rate in the four solid tumor cell lines used (ras gene mutation rate inversely correlated with average cell number couplied, r = 0.98) i.e., showing that high ras gene mutation is closely correlated with loss of GJIC in these malignant human tumor cells; 2. the antitumor effect of the monoterpene d-limonene and the phenol compound, SMD, might be related to the inhibition of P21ras membrane association and enhancement of GJIC, whilst that of the others may be by a different mechanism; 3. the inhibition of P21ras membrane association is directly related to the enhancement of gap junction intercellular communication.

Antineoplastic Agents, Phytogenic↗
PubMed1985

Studies on the mechanism of phorbol ester-induced inhibition of intercellular junctional communication.

Intercellular gap-junctional communication was measured using [14C]citrulline incorporation in co-cultures of argininosuccinate lyase-deficient human fibroblasts and argininosuccinate synthetase-deficient Chinese Hamster V79 cells. As previously shown, in this system junctional communication is completely inhibited by the tumor promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). In the absence of extracellular calcium, TPA inhibition was less pronounced. However, synergism with calcium ionophore A23187 could not be demonstrated. Chlorpromazine, trifluoperazine and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester partially antagonised the effect of TPA. No antagonism was demonstrable between calmidazolium and TPA. Treatment of co-cultures with exogenous phospholipase C or 1-oleoyl-2-acetylglycerol (OAG) resulted in communication inhibition, suggesting that protein kinase C activation is involved in the mechanism of phorbol ester-mediated communication inhibition. However co-cultures which had been made refractory to TPA by prolonged exposure to high concentrations remained sensitive to inhibition by phospholipase C and OAG. These results suggest either that diacylglycerol can produce other effects independent of protein kinase C activation, or that refractoriness to phorbol esters is not simply due to a decrease in the amount of protein kinase C.

Animals↗
PubMed1983

Freeze-fracture study of the hamster ovary surface epithelium intercellular junctions.

The apical intercellular junctions between the hamster ovary surface epithelial cells were studied by freeze-fracture. The results showed tight junctions consisting of intertwining ridges on P faces and complementary furrows on E faces. Typical gap junctions, in the form of clusters of particles on P faces and complementary pits on E faces, were also observed associated with the tight junctional elements. Sometimes the gap junction are the outermost element of the junctional complexes. These observations explain data previously obtained in tracer experiments with lanthanum.

Animals↗
PubMedDate not supplied

Limitations of the scrape-loading/dye transfer technique to quantify inhibition of gap junctional intercellular communication.

Gap junctional intercellular communication (GJIC) is recognized as playing an important role in normal cell proliferation and development. Chemically induced alteration of GJIC has been proposed to be associated with abnormal cellular growth and/or tumor promotion. Several in vitro assays are currently used to determine the effects of chemicals on GJIC between cultured mammalian cells. One of these assays, the scrape-loading dye transfer (SL/DT) technique, is based on monitoring the transfer of the fluorescent dye Lucifer yellow from one cell into adjacent cells via functional gap junctions. The objective of our study was to evaluate and compare various approaches for quantifying results obtained with the SL/DT technique. Confluent cultures of either WB rat liver epithelial cells or LC-540 rat leydig cells were exposed to the animal tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), solvent (0.1% ethanol), or culture medium for one hour at 37 degrees C prior to analysis of GJIC. Inhibition of dye transfer was clearly evident following TPA exposure. Quantification of this dye transfer was assessed via four approaches: manually counting the number of labeled cells; measuring the distance of dye travel from the scrape line; quantifying the amount of cellular dye uptake; and determining the distribution of dye away from the scrape line. Our results suggest that while the SL/DT technique can be effectively used as a tool to determine the qualitative presence or absence of GJIC, its use in quantifying changes in GJIC following chemical exposure is limited. Since concentration-dependent responses are critical in chemical testing, application of the SL/DT method should be restricted to a screening assay for qualitatively assessing the presence or absence of GJIC.

Animals↗
PubMed1996

A characterization of pervanadate, an inducer of cellular tyrosine phosphorylation and inhibitor of gap junctional intercellular communication.

Gap junctional intercellular communication (GJIC), phosphorylation status of the gap junction protein, connexin43 (Cx43), and cellular tyrosine phosphorylation in Syrian hamster embryo cells have been employed for a biological characterization of pervanadate (a mixture of H2O2 and vanadate). In addition, electron paramagnetic resonance (EPR) spectroscopy was used to follow the appearance and disappearance of vanadyl (V(IV)). It has previously been suggested that pervanadate is vanadyl hydroperoxide (V(4+)OOH). This assumption was tested by using mixtures with different molar ratios of H2O2 and orthovanadate, metavanadate or vanadyl sulfate. The maximal biological activity of the mixtures were found at a molar ratio of 2:1 (H2O2:orthovanadate or metavanadate) or 2.5:1 (H2O2:alkaline vanadyl sulfate). No V(IV) EPR spectrum appeared upon mixing orthovanadate or metavanadate and H2O2. The V(IV) EPR spectrum disappeared when vanadyl sulfate was incubated with H2O2 in a 0.5:1 molar ratio (H2O2:alkaline vanadyl sulfate). Spectrophotometrically, a V(V)-like peak at 265 nm had its optimum at this ratio. These results are consistent with pervanadate being diperoxovanadate. The individual compounds were prominently less active than the per-compound mixtures in affecting the biological parameters. The decreases in GJIC showed a concentration-dependent correlation with the onset of the alterations of the Cx43 band pattern and the amount of phosphotyrosine in cellular proteins, but the correlation was not absolute. All the studied biological parameters were reversible, also under continuous exposure to pervanadate.

Animals↗
PubMed1998

Co-culture of two MDCK strains with distinct junctional protein expression: a model for intercellular junction rearrangement and cell sorting.

Distinct epithelial MDCK cell strains displaying extremes in transepithelial electrical resistance (paracellular permeability) have been established in co-culture and the subsequent cellular behaviour and formation of junctional complexes investigated. After high-density seeding, MDCK strain I and II cells in co-culture are initially randomly distributed but subsequently sort themselves out in a time-dependent manner to form separate homotypic aggregates. The final pattern of cell arrangement of homotypic aggregates depends on the relative seeding proportion of each cell type. Immunostaining of established marker proteins for junctional complexes has revealed that MDCK I and II cells differ in the degree of expression of the zonula-adherens-associated protein, E-cadherin, their cytoskeletal architecture and the junctional distribution of a desmosomal protein, and by showing subtle differences in tight junction staining for the zona-occludens-associated proteins, ZO-1 and occludin. The distinct pattern of junctional protein expression is maintained when the two MDCK strains are co-cultured; however, morphologically atypical intercellular junctions between heterotypic cells at the boundary of homotypic cell aggregates have been observed. It has been suggested that cell sorting, a phenomenon yet to be completely understood, is involved in important morphogenetic processes. We propose that co-culture of strains of the well-characterised MDCK cell line may be a novel but well-defined cell system for studying epithelial cell rearrangement and sorting in intact epithelial sheets.

Animals↗
PubMed1990

[Morphologic characteristics of intercellular junctions in early embryogenesis of mice].

Dynamics concerning certain intercellular junctions have been followed during the preimplantation period of development in mouse embryos. The morphological analysis of the preimplantational embryos has demonstrated, that at the initial stages of cleavage (2-4 blastomeres) the cells make contacts by means of nonspecific junctions. Specialized intercellular junctions appear at the stage of 8 blastomeres and are presented as dotted tight and gap junctions. When the embryo is developing from the stage of 8 up to the stage of 16 blastomeres, certain connective complexes appear, consisting of dotted or cord-like tight and gap junctions. At the late morula stage, the external blastomeres in the apical part have contacts with each other by means of cingular tight junctions. In this place a connective complex might emerge; it is displayed as a tight junction and one or two gap junctions. At the blastocyst stage desmosomes and adhision zones appear. Between trophectodermal cells a connective complex arises; it is presented in the slice as a tight cingular junction, desmosomes (as a rule two) and an adhision zone. Between cells of the internal cellular mass the intercellular junctions are presented as dotted tight and gap junctions. Cells of the polar trophoectoderm and cells of the internal cellular mass could have contacts by means of gap and dotted tight junctions.

Animals↗
PubMed1999

Quiescent mammary epithelial cells have reduced connexin43 but maintain a high level of gap junction intercellular communication.

Gap junctions have been implicated in growth control, but it remains unclear whether cells that enter a quiescent state continue to express connexins and maintain a high level of gap junction intercellular communication (GJIC). To this end, MAC-T cells, a bovine mammary epithelial cell line, were serum starved for 48 h to induce a quiescent (G0) state. In quiescent cells, [3H]thymidine incorporation was reduced by 97.3% from serum-fed controls. Western blotting in conjunction with Phosphorlmager analysis revealed up to a 20-fold decrease in the expression of the gap junction protein connexin43 (Cx43 or alpha 1) and a shift toward the unphosphorylated form in quiescent cells. However, cell-to-cell transfer of the gap junction-permeable fluorescent tracer, Lucifer yellow, was only moderately reduced in quiescent cells. In control cells, Cx43 was predominantly perinuclear, although it was also present at sites of cell-cell apposition. In quiescent cells, intracellular labeling for Cx43 decreased without a corresponding reduction at areas of cell-cell contact. Recovery from serum deprivation resulted in increased thymidine incorporation that corresponded with an elevation in Cx43 protein expression and phosphorylation. In parallel studies, MAC-T cells were also induced to enter a quiescent state through contact inhibition. Despite a 20-fold reduction in 5-bromo-2'-deoxyuridine and a substantial reduction in intracellular Cx43, contact inhibited MAC-T cells also maintained gap junctions and GJIC. These experiments demonstrate that the maintenance of dye coupling in quiescent mammary cells is correlated with a redistribution of intracellular stores of Cx43.

Animals↗
PubMed2000

Differentiation of human fetal osteoblastic cells and gap junctional intercellular communication.

Gap junctional channels facilitate intercellular communication and in doing so may contribute to cellular differentiation. To test this hypothesis, we examined gap junction expression and function in a temperature-sensitive human fetal osteoblastic cell line (hFOB 1.19) that when cultured at 37 degrees C proliferates rapidly but when cultured at 39.5 degrees C proliferates slowly and displays increased alkaline phosphatase activity and osteocalcin synthesis. We found that hFOB 1.19 cells express abundant connexin 43 (Cx43) protein and mRNA. In contrast, Cx45 mRNA was expressed to a lesser degree, and Cx26 and Cx32 mRNA were not detected. Culturing hFOB 1. 19 cells at 39.5 degrees C, relative to 37 degrees C, inhibited proliferation, increased Cx43 mRNA and protein expression, and increased gap junctional intercellular communication (GJIC). Blocking GJIC with 18alpha-glycyrrhetinic acid prevented the increase in alkaline phosphatase activity resulting from culture at 39.5 degrees C but did not affect osteocalcin levels. These results suggest that gap junction function and expression parallel osteoblastic differentiation and contribute to the expression of alkaline phosphatase activity, a marker for fully differentiated osteoblastic cells.

Alkaline Phosphatase↗
PubMed1993

[Development of intercellular junction in the human vestibular receptors. A freeze-fracture study].

The intercellular junctions, especially the tight junctions of the inner ear end-organs are considered to act as a barrier to maintain gradients of ions between the endolymph and the perilymph. Thus, the intercellular junctions are of great importance for the function of the inner ear. We have studied the development of intercellular junctions in vestibular end-organs in order to establish a morphological basis for better understandings of the key stage of the development of vestibular end-organs. In the present article, the development and maturation of intercellular junctions in human vestibular receptors were observed with freeze-fracture technique. Junctional complex was already present during 8 weeks of gestation. During 8-11 weeks, a rapid development was seen in the intercellular junctions, so that this period seemed to be the key stage in the development and maturation of intercellular junctions. By the end of 11 weeks, the intercellular junctions had possessed the mature appearance as those seen in adults.

Epithelium↗