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At least 793 records · Page 44Linked to original sources
PubMed2005

Nicotinic cholinergic intercellular communication: implications for the developing auditory system.

In this paper, research on the temporal and spatial distribution of cholinergic-related molecules in the lower auditory brainstem, with an emphasis on nicotinic acetylcholine receptors (nAChRs), is reviewed. The possible functions of acetylcholine (ACh) in driving selective auditory neurons before the onset of hearing, inducing glutamate receptor gene expression, synaptogenesis, differentiation, and cell survival are discussed. Experiments conducted in other neuronal and non-neuronal systems are drawn on extensively to discuss putative functions of ACh and nAChRs. Data from other systems may provide insight into the functions of ACh and nAChRs in auditory processing. The mismatch of presynaptic and postsynaptic markers and novel endogenous agonists of nAChRs are discussed in the context of non-classical interneuronal communication. The molecular mechanism that may underlie the many functions of ACh and its agonists is the regulation of intracellular calcium through nAChRs. The possible reorganization that may take place in the auditory system by the exposure to nicotine during critical developmental periods is also briefly considered.

Acetylcholine↗
PubMed2005

Ligament cells stretch-adapted on a microgrooved substrate increase intercellular communication in response to a mechanical stimulus.

An in vitro model was used to investigate the effect of mechanical stimuli on adaptation to load and calcium signaling in aligned medial collateral ligament cells (MCL). This model used a patterned silicone membrane to align the cells parallel with the direction of the microgrooves. Alignment created an architecture that simulated a degree of cell orientation in native ligament tissue. It was hypothesized that aligned ligament cells would be more efficient at calcium wave propagation than cells that were randomly oriented. It was further hypothesized that calcium wave propagation would be greater among cells that were both aligned and subjected to mechanical stretch compared to cells that were aligned but not stretched. Rat MCL cells were loaded with Fura-2AM, a calcium-binding dye, and mechanically indented using a micropipette tip. A ratio-imaging fluorescence technique was used to quantitate the calcium (Ca2+) response. It was concluded that stretching ligament cells prior to stimulation increased their sensitivity to load and their ability to propagate a calcium wave. However, the ability of aligned cells to propagate this wave was not significantly different when compared to nonaligned cells. Treatment of cultures with inhibitors such as apyrase and suramin significantly reduced the number of cells recruited in the calcium response. Hence, it was concluded that ATP released from mechanically stimulated cells was a principal mediator responsible for the rise in intracellular calcium in ligament cells. Further, purinoceptor activation may amplify the signal to alert and recruit more cells in a response to mechanical stimulation.

Adaptation, Physiological↗
PubMed2005

Secretion systems for secondary metabolites: how producer cells send out messages of intercellular communication.

Many secondary metabolites (e.g. antibiotics and mycotoxins) are toxic to the microorganisms that produce them. The clusters of genes that are responsible for the biosynthesis of secondary metabolites frequently contain genes for resistance to these toxic metabolites, such as different types of multiple drug resistance systems, to avoid suicide of the producer strains. Recently there has been research into the efflux systems of secondary metabolites in bacteria and in filamentous fungi, such as the large number of ATP-binding cassette transporters found in antibiotic-producing Streptomyces species and that are involved in penicillin secretion in Penicillium chrysogenum. A different group of efflux systems, the major facilitator superfamily exporters, occur very frequently in a variety of bacteria that produce pigments or antibiotics (e.g. the cephamycin and thienamycin producers) and in filamentous fungi that produce mycotoxins. Such efflux systems include the CefT exporters that mediate cephalosporin secretion in Acremonium chrysogenum. The evolutionary origin of these efflux systems and their relationship with current resistance determinants in pathogenic bacteria has been analyzed. Genetic improvement of the secretion systems of secondary metabolites in the producer strain has important industrial applications.

Acremonium↗
PubMed2005

Intercellular communications within the rat anterior pituitary XI: an immunohistochemical study of distributions of S-100 positive cells in the anterior pituitary of the rat.

The distribution of the S-100 protein cell (folliculo-stellate cell) is very important to our understanding of the regulation of the anterior pituitary. In this study, 10 intact 60-day-old male Wistar-Imamichi rats, were separated equally into two groups. One was used for immunohistochemical study, and the other for electron microscopic analysis. Immunostained pituitary sections with S-100 protein antibody were photographed using a CCD camera equipped with a computer. The S-100 protein cells were then measured using NIH image software, and the three-dimensional distribution of the cells was analyzed. The distribution of the cells observed in each serial section showed that S-100 protein cells were dense at the basal zone of the gland and at the "transitional zone" where the pars tuberalis adjoined the anterior and intermediate lobes, where they represented over 50% of the total cell population. They then decreased in number with distance from this region to mid-way towards the sagittal axis before increasing again in the tail of the gland. The population of cells also decreased with increasing distance from the "transitional zone" to the wing and with distance from the basal zone. Portal vessels entered the anterior lobe through the "transitional zone" as thick capillaries, ran through the basal surface and penetrated into the central area of the anterior lobe. In all planes, S-100 protein cells encircled the capillaries. Ultrastructural observations confirmed the light microscopic findings indicating that clusters of agranular cells were densely located at the "transitional zone" and in the pars tuberalis. The distribution pattern of the folliculo-stellate cells and the capillaries showed good agreement and the spatial relationship between these two is detailed so as to better understand hypophyseal histophysiology.

Animals↗
PubMed2005

Intercellular communications within the rat anterior pituitary XII: immunohistochemical and physiological evidences for the gap junctional coupling of the folliculo-stellate cells in the rat anterior pituitary.

Since Farquhar [1957. "Corticotrophs" of the rat adenohypophysis as revealed by electron microscopy. Anat. Rec. 127, 291] was the first to report the presence of agranular folliculo-stellate cells as corticotrophs in the anterior pituitary gland, there were no reports about electro-physiological characteristics of the folliculo-stellate cells because of its no hormonal activity and the chaotic distribution of the parenchyma cells. Male Wistar rats, aged 7 weeks with weighing 250--300 g, were separated into two groups. One group was used for immunohistochemical and light microscopical studies to detect S-100 protein and connexin 43. The other group was used for the electro-physiological study and then for the electron microscopical study to know the fine structural character of folliculo-stellate cells after the electro-physiological experiment. Clusters of S-100 protein cells (agranulated folliculo-stellate cells) and numerous connexin 43 positive sites on S-100 protein cells were clear in the "transitional zone" at which the pituitary tissue made the transition from the pars tuberalis to the proximal part of the anterior lobe. Penetration of electrodes to the cells distributed in the transitional zone showed stable membrane potential ranged between--27 and--67mV with no spontaneous activity. Random penetration of electrode showed that larger populations of cell ( approximately 80%) had membrane potentials with -55.6+/-5.1 mV, and less than 20% of cells had the resting membrane potential with -36.0+/-4.4 mV. There were two types of cell couplings; one major group for the recordings from cells with similar deep resting membrane potentials and the other for the recordings from cells with different resting membrane potentials. The former indicated that two cells were electrically coupled while the latter no electrical couples were observed. Carbenoxolone depolarized the membrane by 12.3+/-5.5 mV and reduced the amplitude of electrotonic potentials, and the response recovered by removal of carbenoxolone by the superfusate. The transitional zones of the pituitary glands examined the electrical coupling were observed by an electron microscopy. Almost cytological profiles were observed as intact. The results clearly indicated that the folliculo-stellate cell system deeply participated in the regulation of the anterior pituitary parallel with the portal vessel system, which was the main regulatory system for pituitary hormone secretion.

Animals↗
PubMed2006

Ochratoxin A alters cell adhesion and gap junction intercellular communication in MDCK cells.

Ochratoxin A (OTA) is one of the most potent renal carcinogens studied to date, but the mechanism of tumor formation by ochratoxin A remains largely unknown. Cell adhesion and cell-cell communication participate in the regulation of signaling pathways involved in cell proliferation and growth control and it is therefore not surprising that modulation of cell-cell signaling has been implicated in cancer development. Several nephrotoxicants and renal carcinogens have been shown to alter cell-cell signaling by interference with gap junction intercell communication (GJIC) and/or cell adhesion, and the aim of this study was to determine if disruption of cell-cell interactions occurs in kidney epithelial cells in response to OTA treatment. MDCK cells were treated with OTA (0-50 microM) for up to 24h and gap junction function was analyzed using the scrape-load/dye transfer assay. In addition, expression and intracellular localization of C x 43, E-cadherin and beta-catenin were determined by immunoblot and immunofluorescence analysis. A clear decrease in the distance of dye transfer was evident following treatment with OTA at concentrations/incubation times which did not affect cell viability. Consistent with the functional inhibition of GJIC, treatment with OTA resulted in a dose-dependent decrease in C x 43 expression. In contrast to C x 43, OTA did not alter total amount of the adherens junction proteins E-cadherin and beta-catenin. Moreover, Western blot analysis of Triton X-100 soluble and insoluble protein fractions did not indicate translocation of cell adhesion molecules from the membrane to the cytoplasm. However, a approximately 78 kDa fragment of beta-catenin was detected in the detergent soluble fraction, indicating proteolytic cleavage of beta-catenin. Immunofluorescence analysis also revealed changes in the pattern of both beta-catenin and E-cadherin labeling, suggesting that OTA may alter cell-adhesion. Taken together, these data support the hypothesis that disruption of cell-cell signaling may contribute to OTA toxicity and carcinogenicity.

Animals↗
PubMed2000

Gap junctional intercellular communication and connexin 43 expression in ovarian carcinoma.

OBJECTIVES: Gap junctions, which are composed of subunits termed connexins, are plasma membrane channels that link the interior of adjacent cells and permit cells to directly exchange small molecules and ions. Loss or dysfunction of gap junctions appears to be important in allowing cancer cells to escape growth regulation. In a previous study we showed that human ovarian surface epithelial cells exhibited extensive gap junctions and expression of connexin 43. These were nearly absent in human ovarian adenocarcinoma cell lines. To ensure that this variation was not artificially produced by culturing techniques, this study evaluated gap junctions and connexin 43 expressions in normal ovaries and in ovarian adenocarcinomas. STUDY DESIGN: Specimens of normal ovaries and ovarian adenocarcinomas were obtained at the time of surgery and flash-frozen in liquid nitrogen. Connexin 43 immunostaining was performed on all specimens. RESULTS: Among the 11 normal ovaries an average of 59% of the surface epithelium stained positively for connexin 43. In contrast, among the 10 ovarian adenocarcinomas only 19% of each specimen stained positively for connexin 43 (P =.01). CONCLUSION: Similar to our studies on human ovarian surface epithelial cells and ovarian adenocarcinoma cell lines, surgical specimens of normal ovary exhibited extensive connexin 43 expression, whereas connexin 43 expression was nearly absent in ovarian adenocarcinomas. It thus appears that the previously reported loss of gap junctions and connexin 43 was actually associated with a neoplastic process, rather than being artificially induced in the laboratory.

Connexin 43↗
PubMed1989

Frequency specificity in intercellular communication. Influence of patterns of periodic signaling on target cell responsiveness.

Cells often communicate by means of periodic signals, as exemplified by a large number of hormones and by the aggregation of Dictyostelium discoideum amebas in response to periodic pulses of cyclic AMP. Periodic signaling allows bypassing the phenomenon of desensitization brought about by constant stimuli. To gain further insight into the efficiency of pulsatile signaling, we analyze the effect of periodic stimulation on the dynamic behavior of a receptor system capable of desensitization toward its ligand. We first show that the receptor system adapts to square-wave stimuli, i.e., the response eventually reaches a steady, periodic pattern after a transient phase. By analyzing the dependence of the response on the characteristics of the square-wave stimulation, we show that there exist a waveform and a period of that signal that result in maximum responsiveness of the target system. Similar results are obtained when the signal takes the more realistic form of a periodically repeated stimulation followed by exponential decay of the ligand. The results are discussed with respect to the role of pulsatile secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus and of periodic signaling by cyclic AMP pulses in Dictyostelium. The analysis accounts for the existence, in both cases, of an optimal frequency and waveform of the periodic stimulus that correspond to maximum target cell responsiveness.

Animals↗
PubMed1992

Pulsatile signaling in intercellular communication. Periodic stimuli are more efficient than random or chaotic signals in a model based on receptor desensitization.

The efficiency of various patterns of pulsatile stimulation is determined in a model in which a receptor becomes desensitized in the presence of its stimulatory ligand. The effect of stochastic or chaotic changes in the duration and/or interval between successive pulses in a series of square-wave stimuli is investigated. Before addressing the effect of random variations in the pulsatile signal, we first extend the results of a previous analysis (Li, Y.X., and A. Goldbeter. 1989. Biophys. J. 55:125-145) by demonstrating the existence of an optimal periodic signal that maximizes target cell responsiveness whatever the magnitude of stimulation. As to the effect of stochastic or chaotic variations in the pulsatile stimulus, three kinds of random distributions are used, namely, a Gaussian and a white-noise distribution, and a chaotic time series generated by the logistic map. All these random distributions are symmetrically centered around the reference value of the duration or interval that characterizes the optimal periodic stimulus yielding maximal responsiveness in target cells. Stochastically or chaotically varying pulses are less effective than the periodic signal that corresponds to the optimal pattern of pulsatile stimulation. The response of the receptor system is most sensitive to changes in the time interval that separates successive stimuli. Similar conclusions hold when stochastic or chaotic signals are compared to a reference periodic stimulus differing from the optimal one, although the effect of random variations is then reduced. The decreased efficiency of stochastic pulses accounts for the observed superiority of periodic versus stochastic pulses of cyclic AMP (cAMP) in Dictyostelium amoebae. The results are also discussed with respect to the efficiency of periodic versus stochastic or chaotic patterns of hormone secretion.

Analysis of Variance↗
PubMed2001

Inhibition of gap junctional intercellular communication in rat liver epithelial cells with transforming RNA.

Previous studies indicated that transforming RNA, derived from the 3' half of the U5 small nuclear RNA first stem structure, suppressed the secretory protein translation in vitro. Gap junctions facilitate homeostatic control of cell growth and differentiation and their dysfunction has been correlated with carcinogenesis. Here, we reported that transforming RNA directly suppressed the gap junction protein, connexin 43, translation and thereby inhibited functional gap junction function in rat epithelial cells. Together with previous data, this implies that altered expression of transforming RNA itself is a potential mechanism in inhibiting gap junction function during carcinogenesis.

Animals↗
PubMed1997

Intercellular communication, tumor promotion and non-genotoxic carcinogenesis: relationships based upon structural considerations.

An SAR model for inhibition of metabolic cooperation (iMC) was developed. The structural and physicochemical features associated with the ability to cause iMC are primarily lipophilic moieties consistent with the possibility that they represent receptor-binding ligands. There are also significant parallels between the structural descriptors associated with iMC and those associated with tumor promotion and with carcinogenesis in rodents. Overall, the present study provides structural evidence that iMC is a feature associated with the carcinogenic process.

Animals↗
PubMed2001

HSV-2 disrupts gap junctional intercellular communication between mammalian cells in vitro.

Infection by herpes simplex virus-2 (HSV-2) disrupts both dye and electrical coupling in Vero (African green monkey kidney) cell cultures. Vero cells in vitro were iontophoretically injected with the fluorescent dye Lucifer yellow CH, the spread of which revealed that cells throughout the confluent sheet shared open gap junctions. However, 24 h after infection with the virus (but before cells became rounded), dye always remained only within the target cell. Intracellular electrophysiological measurements of ionic coupling revealed a 0.4 coupling coefficient for adjacent cells in uninfected control cultures. By 3 h following infection significant down-regulation of gap junctions had begun, preceding by many hours any signs of infection visible with the light microscope. Measurements between adjacent cells 3 h post-infection, a period when HSV-2 gene expression is known to be at a maximum, yielded an average coupling coefficient of 0.35. By 6 h post-infection (a period of known viral DNA replication) average coupling coefficient for adjacent cells was 0.25, while by 24 h post-infection the average fill still further to <0.08. A coupling coefficient of <0.08 suggests that infection by HSV-2 completely disabled the gap junctions.

Animals↗