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PubMedDate not supplied

Electrotonic transmission within pericyte-containing retinal microvessels.

OBJECTIVE: Little is known about the electrotonic architecture of the pericyte-containing retinal microvasculature. Here, the authors focus on the cell-to-cell transmission of hyperpolarization, which can induce abluminal pericytes to relax and lumens to dilate. METHODS: With perforated-patch pipettes, the authors monitored the membrane potentials and ionic currents of pairs of pericytes located on freshly isolated rat retinal microvessels. Voltage changes were induced by administering electrical stimuli into pericytes, miniperfusing the KATP channel opener pinacidil, or using oxotremorine to activate chloride channels. RESULTS: Suggestive of extensive cell-to-cell communication, spontaneous voltage changes were strikingly similar in widely separated pericytes. In addition, injection of current into one of a pair of sampled pericytes always elicited a voltage response in the other sampled pericyte; the gap junction uncoupler, heptanol, blocked this transmission. In the dual recordings, hyperpolarization spreading from a current-injected pericyte decayed approximately 40% within 100 microm. In contrast, pinacidil-induced hyperpolarizations diminished by only approximately 2% in 100 microm. Depolarizations also appeared to spread with similar transmission efficacies. CONCLUSIONS: Based on the experiments, the authors propose that key features of the electrotonic architecture of retinal microvessels include highly efficient cell-to-cell communication within the endothelium and relatively inefficient transmission at pericyte/endothelial junctions. Thus, the endothelium is likely to provide an efficient pathway that functionally links contractile pericytes and thereby, serves to coordinate the vasomotor response of a retinal capillary.

Animals↗
PubMed1979

Intercellular communication in pancreatic islet monolayer cultures: a microfluorometric study.

Single islet cells in monolayer cultures of neonatal rat pancreas were microinjected with fluorescein and scanned topographically by microfluorometry. Fluorescein spread from an injected islet cell directly into neighboring islet cells, and, in the presence of 16.7 millimolar glucose, significantly more islet cells communicated with the injected cell than in glucose-free medium. Islet cells were also microinjected with glycolytic substrates and activators that produced transient changes in cellular levels of reduced pyridine nucleotides-nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate [NAD(P)H]. Changes in NAD(P)H fluorescence were observed in islet cells incubated first for 18 hours in very low glucose concentrations and then in a glucose-free medium and injected with glycolytic substrates and activators; however, little change of fluorescence occurred in adjacent islet cells. In contrast, after adding 16.7 millimolar glucose to the medium, injection of glycolytic substrates and activators produced transient changes in NAD(P)H fluorescence in the injected cell and in neighboring cells.

Animals↗
PubMed2001

Role of adhesion molecules in activation signaling in T lymphocytes.

The T cell and antigen-presenting cell communicate to initiate an immune response through formation of an immunological synapse. This specialized cell-cell junction is compartmentalized into adhesion molecule and T cell receptor enriched regions or SMACs. Distinct signals seem to be generated in the T cell receptor and adhesion molecule-dominated regions. This review focuses on how these distinct signaling pathways may be integrated within the T cell to set thresholds for T cell activation, proliferation, and survival.

Antigen-Presenting Cells↗
PubMed1989

Spatial regulation of zerknüllt: a dorsal-ventral patterning gene in Drosophila.

zerknüllt (zen) is one of approximately 10 zygotically active genes that control the differentiation of the dorsal-ventral (D/V) pattern during early embryogenesis in Drosophila. Past genetic analyses suggest that maternal factors repress the expression of zen in ventral regions, thereby restricting zen products to dorsal and dorsal-lateral regions of precellular embryos. Subsequent interactions with other zygotic D/V regulatory genes refine the zen pattern, restricting expression to the dorsal-most ectoderm. Here we describe the use of zen promoter fusions and P-element transformation to identify cis elements that are responsible for the complex spatial pattern of zen expression. The zen promoter shows a two-tier organization: Distal sequences mediate its initial response to maternal factors, whereas proximal sequences are responsible for the refinement of the pattern in older embryos. The distal regulatory element has the property of a silencer (or anti-enhancer) element and can act over a distance to repress ventral expression of a heterologous promoter. Also, we discuss evidence that proximal promoter sequences interact with factors that may be modulated by a cell-cell communication pathway.

Animals↗
PubMed2000

Chronic hypertension alters the expression of Cx43 in cardiovascular muscle cells.

Connexin43 (Cx43), the predominant gap junction protein of muscle cells in vessels and heart, is involved in the control of cell-to-cell communication and is thought to modulate the contractility of the vascular wall and the electrical coupling of cardiac myocytes. We have investigated the effects of arterial hypertension on the expression of Cx43 in aorta and heart in three different models of experimental hypertension. Rats were made hypertensive either by clipping one renal artery (two kidney, one-clip renal (2K,1C) model) by administration of deoxycorticosterone and salt (DOCA-salt model) or by inhibiting nitric oxide synthase with N G-nitro-L-arginine methyl ester (L-NAME model). After 4 weeks, rats of the three models showed a similar increase in intra-arterial mean blood pressure and in the thickness of the walls of both aorta and heart. Analysis of heart mRNA demonstrated no change in Cx43 expression in the three models compared to their respective controls. The same 2K,1C and DOCA-salt hypertensive animals expressed twice more Cx43 in aorta, and the 2K, 1C rats showed an increase in arterial distensibility. In contrast, the aortae of L-NAME hypertensive rats were characterized by a 50% decrease in Cx43 and the carotid arteries did not show increased distensibility. Western blot analysis indicated that Cx43 was more phosphorylated in the aortae of 2K,1C rats than in those of L-NAME or control rats, indicating a differential regulation of aortic Cx43 in different models of hypertension. The data suggest that localized mechanical forces induced by hypertension affect Cx43 expression and that the cell-to-cell communication mediated by Cx43 channels may contribute to regulating the elasticity of the vascular wall.

Animals↗
PubMed2000

Connexin gene expression in seminiferous tubules of the Sprague-Dawley rat.

Sertoli and spermatogenic cells establish germ cell- and epithelial stage-dependent networks of cell-cell communication thought to be important for the initiation and maintenance of spermatogenesis. Since gap junctions assemble between Sertoli cells and between Sertoli and spermatogenic cells, it was hypothesized that multiple, unique routes of cell-cell communication may be established, in part, by the assembly of structurally diverse gap junctions from the connexin (Cx) multigene family. Differences in channel structure may support differences in ion or second messenger permeability between cell types. Reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that 11 Cx mRNAs were present in total RNA from seminiferous tubules and that 10 of the Cx mRNAs were present in polysomes and presumably translated. RT-PCR analyses also showed that the Cx mRNA population varied between different seminiferous tubule cell types. There were 9 Cx mRNAs in germ cells, 8 in Sertoli cells, and 5 in peritubular cells. One of the Cx mRNAs, Cx-50, was detected only in pachytene spermatocytes and round spermatids. Comparisons of the Cx mRNAs present in tubules at different postnatal ages showed that at least 2 Cxs (Cx-33 and Cx-50) accumulated when leptotene-zygotene stages developed. The multiple Cx genes and proteins produced in spermatogenesis may support the assembly of structurally diverse gap junctions.

Animals↗
PubMed2006

A cellular automaton model for the migration of glioma cells.

We present a study of in vitro cell migration in two dimensions as a first step towards understanding the mechanisms governing the motility of glioma cells. Our study is based on a cellular automaton model which aims at reproducing the kinetics of a lump of glioma cells deposited on a substrate of collagen. The dynamical effects of cell attraction and motion inertia are introduced through adequate automaton rules. We compare the density profiles given by the model to those obtained experimentally. The result of the best fit indicates a substantial cell-cell attraction due to cell-cell communication through gap junctions (or chemotaxis) and negligible inertia effects during migration. Tracking of individual migrating cells indicates highly convoluted cell trajectories.

Algorithms↗
PubMed2006

Dodeca-CLE peptides as suppressors of plant stem cell differentiation.

In plants and animals, small peptide ligands that signal in cell-cell communication have been suggested to be a crucial component of development. A bioassay of single-cell transdifferentation demonstrates that a dodecapeptide with two hydroxyproline residues is the functional product of genes from the CLE family, which includes CLAVATA3 in Arabidopsis. The dodecapeptide suppresses xylem cell development at a concentration of 10(-11) M and promotes cell division. An application, corresponding to all 26 Arabidopsis CLE protein family members, of synthetic dodecapeptides reveals two counteracting signaling pathways involved in stem cell fate.

Amino Acid Sequence↗
PubMed1991

Dictyostelium discoideum lipids modulate cell-cell cohesion and cyclic AMP signaling.

During Dictyostelium discoideum development, cell-cell communication is mediated through cyclic AMP (cAMP)-induced cAMP synthesis and secretion (cAMP signaling) and cell-cell contact. Cell-cell contact elicits cAMP secretion and modulates the magnitude of a subsequent cAMP signaling response (D. R. Fontana and P. L. Price, Differentiation 41:184-192, 1989), demonstrating that cell-cell contact and cAMP signaling are not independent events. To identify components involved in the contact-mediated modulation of cAMP signaling, amoebal membranes were added to aggregation-competent amoebae in suspension. The membranes from aggregation-competent amoebae inhibited cAMP signaling at all concentrations tested, while the membranes from vegetative amoebae exhibited a concentration-dependent enhancement or inhibition of cAMP signaling. Membrane lipids inhibited cAMP signaling at all concentrations tested. The lipids abolished cAMP signaling by blocking cAMP-induced adenylyl cyclase activation. The membrane lipids also inhibited amoeba-amoeba cohesion at concentrations comparable to those which inhibited cAMP signaling. The phospholipids and neutral lipids decreased cohesion and inhibited the cAMP signaling response. The glycolipid/sulfolipid fraction enhanced cohesion and cAMP signaling. Caffeine, a known inhibitor of cAMP-induced adenylyl cyclase activation, inhibited amoeba-amoeba cohesion. These studies demonstrate that endogenous lipids are capable of modulating amoeba-amoeba cohesion and cAMP-induced activation of the adenylyl cyclase. These results suggest that cohesion may modulate cAMP-induced adenylyl cyclase activation. Because the complete elimination of cohesion is accompanied by the complete elimination of cAMP signaling, these results further suggest that cohesion may be necessary for cAMP-induced adenylyl cyclase activation in D. discoideum.

Adenylyl Cyclases↗
PubMed1976

[On the simultaneous effects of ionising radiation and chemical agents on animal cells. 1st communication. Cytogenetic studies on X-rays and isonicotinic acid hydrazide in the Chinese hamster, Cricetulus griseus (author's transl)].

In bone marrow cells of Chinese hamsters enhanced chromosome damage is observed after 48 h treatment of the animals with isoniazid (INH) combined with X-rays only at much higher doses than normally applied in human therapy. Compared to X-ray-induced aberration levels, 125 mg/kg INH and 50 R given simultaneously increase the number of gaps and breaks, the latter being increased over-additively. This points to an interaction between both agents. The combined treatment changes the mitotic rate of the bone marrow as well.

Animals↗
PubMed2002

Alterations in gap junction protein expression in human benign prostatic hyperplasia and prostate cancer.

PURPOSE: Gap junctions composed of connexin proteins have an essential role in intercellular communication and differentiation. Dysregulation of connexin expression is believed to have a role in carcinogenesis. The human prostate has been reported to express connexin 32 and 43. However, the expression pattern in prostate cancer is controversial, while to our knowledge connexin expression has not been reported in benign prostatic hyperplasia (BPH). To understand the potential involvement in prostate disease connexin 32 and 43 expression was evaluated in a series of normal prostate, BPH and prostate cancer specimens that were surgically removed due to bladder outlet obstruction. MATERIALS AND METHODS: Frozen sections of 23 normal, 43 BPH and 40 cancer involved prostates were evaluated for the presence, staining intensity and pattern of connexin 32 and 43 by immunocytochemical testing. RESULTS: In all specimens examined connexin 43 stain was punctate along the borders of the basal epithelial cells, whereas connexin 32 immunolocalized to luminal epithelial cells. In normal prostate connexin 43 and 32 were present in 87% and 65% of specimens, respectively, at low to moderate stain intensity. Importantly none of the normal samples were negative foreach connexin. In BPH specimens there was a marked increase in the incidence and intensity of connexin 43 and 32 immunostaining within epithelial cells. In addition, 23% of BPH samples showed strong connexin 43 expression in stromal cells. In contrast, connexin was decreased in prostate cancer specimens, of which 65% and 38% were negative for connexin 43 and 32, respectively, and 28% were negative for each type. In poorly differentiated tumors connexin 43 and 32 were present in only 10% and 40% of tumors, respectively, at low immunostaining intensity. CONCLUSIONS: In normal human prostate basal cells communicate via connexin 43 gap junctions, whereas luminal cells communicate via connexin 32 gap junctions. In BPH gap junctional intercellular communication is increased in epithelial and stromal cells, which may have a role in BPH pathogenesis. In prostate cancer gap junctional intercellular communication is decreased, is as indicated by decreased expression of connexin 43 and 32 with severe loss in poorly differentiated prostate cancer. These alterations in connexin expression may have a role in dedifferentiation and tumor progression.

Adenocarcinoma↗
PubMed2001

Alterations in gap junction protein expression in human benign prostatic hyperplasia and prostate cancer.

PURPOSE: Gap junctions composed of connexin proteins have an essential role in intercellular communication and differentiation. Dysregulation of connexin expression is believed to have a role in carcinogenesis. The human prostate has been reported to express connexin 32 and 43. However, the expression pattern in prostate cancer is controversial, while to our knowledge connexin expression has not been reported in benign prostatic hyperplasia (BPH). To understand the potential involvement in prostate disease connexin 32 and 43 expression was evaluated in a series of normal prostate, BPH and prostate cancer specimens that were surgically removed due to bladder outlet obstruction. MATERIALS AND METHODS: Frozen sections of 23 normal, 43 BPH and 40 cancer involved prostates were evaluated for the presence, staining intensity and pattern of connexin 32 and 43 by immunocytochemical testing. RESULTS: In all specimens examined connexin 43 stain was punctate along the borders of the basal epithelial cells, whereas connexin 32 immunolocalized to luminal epithelial cells. In normal prostate connexin 43 and 32 were present in 87% and 65% of specimens, respectively, at low to moderate stain intensity. Importantly none of the normal samples were negative foreach connexin. In BPH specimens there was a marked increase in the incidence and intensity of connexin 43 and 32 immunostaining within epithelial cells. In addition, 23% of BPH samples showed strong connexin 43 expression in stromal cells. In contrast, connexin was decreased in prostate cancer specimens, of which 65% and 38% were negative for connexin 43 and 32, respectively, and 28% were negative for each type. In poorly differentiated tumors connexin 43 and 32 were present in only 10% and 40% of tumors, respectively, at low immunostaining intensity. CONCLUSIONS: In normal human prostate basal cells communicate via connexin 43 gap junctions, whereas luminal cells communicate via connexin 32 gap junctions. In BPH gap junctional intercellular communication is increased in epithelial and stromal cells, which may have a role in BPH pathogenesis. In prostate cancer gap junctional intercellular communication is decreased, is as indicated by decreased expression of connexin 43 and 32 with severe loss in poorly differentiated prostate cancer. These alterations in connexin expression may have a role in dedifferentiation and tumor progression.

Adenocarcinoma↗
PubMed2003

Analysis of gene expression profile induced by EMP-1 in esophageal cancer cells using cDNA Microarray.

AIM: To obtain human esophageal cancer cell EC9706 stably expressed epithelial membrane protein-1 (EMP-1) with integrated eukaryotic plasmid harboring the open reading frame (ORF) of human EMP-1, and then to study the mechanism by which EMP-1 exerts its diverse cellular action on cell proliferation and altered gene profile by exploring the effect of EMP-1. METHODS: The authors first constructed pcDNA3.1/myc-his expression vector harboring the ORF of EMP-1 and then transfected it into human esophageal carcinoma cell line EC9706. The positive clones were analyzed by Western blot and RT-PCR. Moreover, the cell growth curve was observed and the cell cycle was checked by FACS technique. Using cDNA microarray technology, the authors compared the gene expression pattern in positive clones with control. To confirm the gene expression profile, semi-quantitative RT-PCR was carried out for 4 of the randomly picked differentially expressed genes. For those differentially expressed genes, classification was performed according to their function and cellular component. RESULTS: Human EMP-1 gene can be stably expressed in EC9706 cell line transfected with human EMP-1. The authors found the cell growth decreased, among which S phase was arrested and G1 phase was prolonged in the transfected positive clones. By cDNA microarray analysis, 35 genes showed an over 2.0 fold change in expression level after transfection, with 28 genes being consistently up-regulated and 7 genes being down-regulated. Among the classified genes, almost half of the induced genes (13 out of 28 genes) were related to cell signaling, cell communication and particularly to adhesion. CONCLUSION: Overexpression of human EMP-1 gene can inhibit the proliferation of EC9706 cell with S phase arrested and G1 phase prolonged. The cDNA microarray analysis suggested that EMP-1 may be one of regulators involved in cell signaling, cell communication and adhesion regulators.

Cell Division↗
PubMed1979

Transmembrane communication in cells chronically infected with measles virus.

The transmembrane association of the measles virus hemagglutinin and hemolysin surface proteins with intracellular viral antigens was studied. Rabbit antisera monospecific for measles virus matrix and nucleocapsid proteins and a human antiserum containing specificities for both the hemagglutinin and hemolysin proteins were used to study the co-capping of these proteins in human Lu 106 cell-line, chronically infected with measles virus. Capping of the surface-associated envelope components was accompanied by co-capping of the matrix and nucleocapsid proteins, the latter being localized mainly within the inclusions. This demonstrated transmembrane communication between surface-associated envelope components and the intracellular measles virus matrix and nucleocapsid proteins. The results demonstrated the existence of a linkage between viral inclusions and viral proteins associated with cell membranes. In the presence of cytochalasin B (1--2 micrograms/ml), co-capping of the matrix protein was unchanged or slightly enhanced, whereas co-capping of the nucleocapsid protein decreased, indicating that actin filaments may mediate the communication between viral nucleocapsids and the cell membrane.

Antigens, Surface↗
PubMed2005

A synthetic multicellular system for programmed pattern formation.

Pattern formation is a hallmark of coordinated cell behaviour in both single and multicellular organisms. It typically involves cell-cell communication and intracellular signal processing. Here we show a synthetic multicellular system in which genetically engineered 'receiver' cells are programmed to form ring-like patterns of differentiation based on chemical gradients of an acyl-homoserine lactone (AHL) signal that is synthesized by 'sender' cells. In receiver cells, 'band-detect' gene networks respond to user-defined ranges of AHL concentrations. By fusing different fluorescent proteins as outputs of network variants, an initially undifferentiated 'lawn' of receivers is engineered to form a bullseye pattern around a sender colony. Other patterns, such as ellipses and clovers, are achieved by placing senders in different configurations. Experimental and theoretical analyses reveal which kinetic parameters most significantly affect ring development over time. Construction and study of such synthetic multicellular systems can improve our quantitative understanding of naturally occurring developmental processes and may foster applications in tissue engineering, biomaterial fabrication and biosensing.

4-Butyrolactone↗
PubMed1996

Intercellular communication within the rat anterior pituitary gland: VI. Development of gap junctions between folliculo-stellate cells under the influence of ovariectomy and sex steroids in the female rat.

BACKGROUND: Farquhar (1957) initially described the folliculo-stellate cells in the rat anterior pituitary gland and found them to be located in groups around follicles throughout the anterior lobe. Soji and his co-workers have published a series of reports concerning cell-to-cell communication in the male rat hypophysis involving folliculo-stellate cells as mediated through a gap junctional network and recorded a reduction in junctional number following castration that was reversed by the administration of testosterone (Soji and Herbert, 1990, Anat. Rec., 226:342-346; Soji et al., 1990, Anat. Rec., 226:337-341). METHODS: Animals were ovariectomized at 10 days of age and separated into three groups: (1) intact control, (2) ovariectomized controls, (3) ovariectomized and given either estradiol, testosterone, or progesterone. On days 10, 20, 30, 40, and 45, the pituitary gland from animals in each group was removed and processed for ultrastructural examination. RESULTS: Gap junctions in the intact control female rats initially appeared between adjacent folliculo-stellate cells on day 20. Their numbers linearly increased until the animals reached the age of 45 days. In contrast, there was a suppression in the number of gap junctions present in the ovariectomized groups and a marked enhancement of the junctions in each of the three steroid-treated groups. CONCLUSIONS: These findings support the observations made in the male rat in which it was found that the development of gap junctions in the anterior pituitary gland of the rat is dependent in part on the presence of sex steroid hormones.

Animals↗
PubMed2005

Differentiation of circulating endothelial progenitor cells to a cardiomyogenic phenotype depends on E-cadherin.

Progenitor cells may contribute to cardiac regeneration. Here, we investigated the role of cadherins and integrins for differentiation of human adult circulating endothelial progenitor cells (EPCs) into cardiomyocytes (CM) in a co-culture system. N- and E-cadherin were expressed in EPCs and were localized at the interface between EPCs and CM. Incubation of a blocking antibody against E-cadherin reduced the expression of CM marker protein in EPCs. Blocking antibodies against N- or P-cadherin or the beta1- and beta2-integrins were not effective. These data suggested that cell-to-cell communication mediated by E-cadherin contributes to the acquirement of a cardiomyogenic phenotype of human endothelial progenitor cells.

Antibodies, Blocking↗
PubMed2003

ACTH occurrence in teleosts supramedullary neuron clusters: a neuron-glial common language?

The cross-talk between neurons and glia is receiving increased attention because of its potential role in information processing in the nervous system. We choose the cluster of supramedullary neurons (SN) and glial cells of pufferfish as a suitable model for studying neuron-glial interactions, identifying the implicated cell types and the signalling involved. In particular, among proopiomelanocortin (POMC)-derived peptides, adrenocorticotrope hormone (ACTH)-immunopositivity was found both in SN and in microglial cells. The present results for the first time show the presence of ACTH in microglia of a vertebrate. The role of ACTH is discussed, including its possible neuroprotective function. Moreover, SN immunoreactivity supports the idea that ACTH participates in neurotransmission and/or neuromodulation. In addition to these possible functions, the hypothesis is put forward that ACTH represents a common language by which neurons and glial cells communicate with each other.

Adrenocorticotropic Hormone↗