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At least 613 records · Page 34Linked to original sources
PubMed2000

Bystander effect in herpes simplex virus-thymidine kinase/ganciclovir cancer gene therapy: role of gap-junctional intercellular communication.

Antitumor suicide gene therapy is one of the emerging strategies against cancer. It consists of the introduction into cancer cells of a gene capable of converting a nontoxic prodrug into a cytotoxic drug. Because this therapeutic gene cannot be easily introduced into the whole cell population of a tumor, the successful eradication of tumors depends on a phenomenon called the "bystander effect," by which the introduced gene can affect even cells in which it is not itself present. From a therapeutic point of view, it may be crucial to enhance this phenomenon through various means to achieve tumor eradication. One such suicide gene, the thymidine kinase gene from the herpes simplex virus, in combination with the prodrug ganciclovir, has been extensively and successfully used in some animal models exhibiting a strong bystander effect. Among the mechanisms involved in this phenomenon, gap junctional intercellular communication (GJIC) is directly involved in the transfer of the toxic metabolites of ganciclovir, which pass directly from herpes simplex virus thymidine kinase-expressing cells to surrounding cells that do not express it. Because GJIC appears to be a mediator of the bystander effect both in vitro and in vivo, here we review possible molecular strategies for enhancing the extent of tumor cell death by increasing the intratumoral GJIC capacity.

Animals↗
PubMed2007

Versican modulates gap junction intercellular communication.

Versican is a large chondroitin sulfate proteoglycan and belongs to the family of lecticans. Versican possesses two globular domains, G1 and G3 domain, separated by a CS-attachment region. The CS-attachment region present in the middle region is divided into two spliced domains named CSalpha and beta. Alternative splicing of versican generates at least four versican isoforms named V0, V1, V2, and V3. We have successfully cloned the full-length cDNA of chick versican isoforms V1 and V2 and found that versican isoform V1 induced mesenchymal-epithelial transition in NIH3T3 cells. Mesenchymal-epithelial transition induced by V1 in NIH3T3 cells is characterized by expression of E-cadherin and occludin, two epithelial markers, and reduced expression of fibroblastic marker vimentin (Sheng et al., 2006, Mol Biol Cell. 17, 2009-2020). In the present studies, we found that versican V1 isoform not only induced cell transition, but also increased intercellular communication via gap junction channels composed of connexin proteins. Our results showed that V1 induces plasma membrane localization of connexin 43, resulting in increased cell communication. This was further confirmed by blocking assays. Gap junctions mediated the transfer of small cytoplasmic molecules and the diffusion of second messenger molecules between adjacent cells. The ability of versican in regulating gap junction implied a potential role of versican in coordinating functions.

Animals↗
PubMed2005

Intercellular communication via gap junctions in activated rat hepatic stellate cells.

BACKGROUND AND AIMS: Gap junctional communication was studied in quiescent and activated hepatic stellate cells. METHODS: Connexin expression and intercellular dye transfer were studied in rat hepatic stellate cells in culture and in vivo. RESULTS: Protein expression of connexin 43 was up-regulated in activated hepatic stellate cells in vivo and in vitro and was mainly localized on the cell surface, whereas connexin 26 was found intracellularly. In contrast to hepatocytes, hepatic stellate cells do not express connexin 32. Confluent hepatic stellate cells in culture communicate via gap junctions, resulting in lucifer yellow transfer and propagation of intracellular calcium signals. Phorbol ester induces a protein kinase C-dependent hyperphosphorylation and degradation of connexin 43 and inhibits intercellular communication on a short-term time scale. At the long-term level, vitamin D(3) , lipopolysaccharide, thyroid hormone T(3), dexamethasone, platelet-derived growth factor, endothelin 1, and interleukin 1beta up-regulate connexin 43 protein and messenger RNA expression and enhance intercellular communication. Slight down-regulation of connexin 43 is observed in response to vitamin A. Connexin 43 induction by endothelin 1 is inhibited by both endothelin A and endothelin B receptor antagonists. In coculture systems, hepatic stellate cells communicate with each other, which is suggestive of a syncytial organization, but no communication was found between hepatic stellate cells and other liver cell types. As shown by immunohistochemistry and electron microscopy, gap junctions are formed between activated hepatic stellate cells in vivo. CONCLUSIONS: Gap junctional communication occurs between hepatic stellate cells, is enhanced after activation, and underlies complex regulation by cytokines, hormones, and vitamins.

Animals↗
PubMed2001

Bystander effect in uracil phosphoribosyltransferase/5-fluorouracil-mediated suicide gene therapy is correlated with the level of intercellular communication.

We examined whether a suicide gene/prodrug system using the uracil phosphoribosyltransferase (UPRT) of E. coli origin and 5-fluorouracil (5-FU) could achieve a bystander effect in two rodent tumor cell lines, murine colon carcinoma (Colon 26) and rat gliosarcoma (9L) cells. Cytotoxicity tests of mixed populations consisting of parent and transduced cells showed that the bystander effect was not produced in Colon 26 cells in either the UPRT/5-FU system or the herpes simplex virus-thymidine kinase/ganciclovir system but a strong bystander effect was evidenced by both suicide gene systems in 9L cells. The expression level of connexin 43, a protein that constitutes gap junctions, was high in 9L but low in Colon 26 cells. A gap junction-permeable fluorescein dye could be transferred among 9L cells but hardly at all among Colon 26 cells. Taken together, the efficacy of the bystander effect in the UPRT/5-FU system can be affected by gap junction-mediated intercellular communication.

Animals↗
PubMed1994

Influence of the herbicide Linuron on growth rate and gap-junctional intercellular communication of cultured endothelial cells.

On the basis of in vivo toxicological long-term tests performed on rodents, the herbicide Linuron [3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea] has been classified by the U.S. Environmental Protection Agency (EPA) (1988) as a class C carcinogen (possibly carcinogenic to humans). However, when Linuron was analyzed for genotoxicity, negative results were obtained. An epigenetic, tumor-promoting potential was hence suspected to be responsible for the oncogenic activity of the molecule. In the absence of in vivo data concerning the tumor-promoting activity of the herbicide and being well established that tumor promoters interfere with the cell growth rate and gap-junctional permeability, the effects of technical grade Linuron and of its trade formulation (Linuron 50) on these parameters were investigated. This is especially important in the case of the formulated preparation for a correct estimate of the health hazard to humans. Cytotoxicity and gap-junctional intercellular communication (GJIC) assays were performed on the endothelial cell line F-BAE GM 7373, an in vitro cell system known to be responsive to the biological effects of tumor promoters. A time- and dose-related cytotoxic effect was found for both Linuron and Linuron 50, the latter being the far more cytotoxic of the two. However, when tested at noncytotoxic concentrations over a period of 48 h, neither Linuron nor Linuron 50 altered the capacity of F-BAE GM 7373 cells to intercommunicate. On the basis of the results obtained, the possibility that Linuron and Linuron 50 are endowed with tumor-promoting activity is discussed. In vivo studies on tumor-promoting and genotoxic activity are in progress to complement the information available on the toxicological properties of Linuron and its trade preparation.

Cell Communication↗
PubMed1998

Intrinsic controls of intracellular calcium and intercellular communication in the regulation of neuroendocrine cell activity.

1. The magnocellular hypothalamoneurohypophysial system, consisting chiefly of the supraoptic and paraventricular nuclei and their axonal projections to the pituitary neural lobe, has become a model for the study of neuroendocrine cell morphology, function, and plasticity. 2. Decades of research have produced a wealth of knowledge about the physiological conditions that activate this system, the peripheral target tissues affected by its outputs, and its capacity to undergo use-dependent, reversible reorganization. 3. Earlier research on the neural control of this system concentrated largely on the synaptic inputs that influence the activity of these magnocellular neurons and, while that task is still far from completed, methods have now been developed that permit insights to be gained into the control exercised by intrinsic cellular and molecular mechanisms. 4. This article reviews the current state of knowledge of roles played by these intrinsic mechanisms, including influences of intracellular calcium buffering, calcium release from internal stores and intercellular communication through gap junctions, in the control of neuroendocrine cell activity.

Animals↗
PubMed1992

Hormonal regulation of intercellular communication: parathyroid hormone increases connexin 43 gene expression and gap-junctional communication in osteoblastic cells.

The presence of gap junctions between osteoblastic cells has been previously reported. For this study we used the rat osteosarcoma cell line UMR 106, which expresses the osteoblastic phenotype, as a model to characterize further the nature, physiology, and regulation of gap junctions. Northern blot analysis identified a 3.0-kilobase RNA species corresponding to the gap junction protein connexin 43. The presence of two other connexin RNA species (26 and 32) could not be detected by this method in these cells. The identified connexin RNA was amplified by reverse transcription coupled to polymerase chain reaction; the sequence of the amplified product appears identical to the sequence of a cloned rat heart connexin 43 gene. After treatment with PTH, forskolin, and 8-Br-cAMP (a cAMP analog), the levels of connexin 43 RNA in UMR 106 cells increased. Further evidence for the role of PTH and cAMP in the physiology of gap junctions in these cells was obtained with Lucifer yellow dye transfer experiments. Gap-junctional intercellular communication increased in response to PTH and forskolin (an inducer of adenylate cyclase activity). Expression of connexin 43 RNA increased severalfold in response to PTH in a concentration- and time-dependent fashion. Connexin 43 RNA and its PTH-mediated stimulation were also observed in several other osteoblastic cell lines. The roles of PTH and forskolin in regulating the physiological state of gap junctions were confirmed in primary cultures of rat calvaria osteoblasts.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Modulation of alpha 1-adrenergic contractility in isolated vascular tissues by heptanol: a functional demonstration of the potential importance of intercellular communication to vascular response generation.

After years of intensive investigation, the mechanism(s) underlying syncytial vascular smooth muscle responses both in vitro and in vivo is still poorly understood. Neither perivascular innervation nor regenerative electrical events appear sufficient to coordinate responses among vascular smooth muscle cells in many blood vessels. The implication of these observations is that another mechanism is required for organizing syncytial vascular responses. Although gap junctions are ubiquitously distributed among vascular wall cells throughout the vascular tree, their contribution to the modulation of vasomotor tone is still considered controversial. Resolution of the long standing debate awaits a clear demonstration that gap junctions modulate contraction or relaxation responses to vascular smooth muscle. Despite the absence of specific gap junctional uncoupling agents, it has still been possible to identify reasonable experimental conditions under which the contribution of gap junctions to contractile responses in isolated vascular tissues could be evaluated. Studies in isolated preparations known to contain gap junctions have indicated that alpha 1-adrenergic receptor-mediated contractile responses of diverse isolated vascular tissues, are significantly modulated by selective disruption of intercellular communication with the well studied lipophilic uncoupling agent heptanol. Interpretation of these pharmacological studies is explicitly dependent on the selectivity of the uncoupling actions of heptanol. Considerable experimental evidence suggests that, at the concentrations used, in the preparations thus far examined, heptanol does indeed have selective uncoupling actions. In fact, recent experiments provide empirical support for an operational definition of the selectivity of heptanol, and a functional role for gap junctions in modulating contractile responses in isolated vascular tissues. The operational definition states only that there exists a narrow, albeit identifiable, concentration range over which it is reasonable to assume that the effects of heptanol are primarily related to its uncoupling actions on gap junctions. The functional role for gap junctions is defined by their requisite contribution to tension development during contraction of isolated tissues. Experimentally, this can be visualized as a significant diminution in the contractile responses of isolated vascular tissues in the presence of selective uncoupling heptanol concentrations. Thus, a cogent interpretation of available data is that they provide compelling indirect evidence for a principle role of gap junctions in modulating the alpha 1-adrenergic contractility of isolated vascular tissues.

Alcohols↗
PubMed1995

Non-genotoxic mechanisms of carcinogenesis: studies of cell transformation and gap junctional intercellular communication.

It is widely accepted that a series of genetic changes accumulate during carcinogenesis. In addition, it is likely that various non-genotoxic mechanisms also operate at different stages of carcinogenesis. It is even possible that non-genotoxic mechanisms indirectly generate genetic changes, e.g., through induction of cell proliferation, active oxygen species or cytosine methylation. This may partially explain why many carcinogens are devoid of activity when tested in the usual genetic toxicology assays. In vitro cell transformation mimics certain stages of in vivo carcinogenesis. It has therefore been proposed that both genotoxic and non-genotoxic aspects of carcinogenesis can be studied in cell transformation systems, with tumor formation by transformed cells in syngenic animals or nude mice as the endpoint. Many genotoxic as well as non-genotoxic carcinogens induce transformation of Syrian hamster embryo, murine Balb/c 3T3 and murine C3H10T1/2 cells; interaction of genotoxic and non-genotoxic mechanisms can be clearly seen in 2-stage cell transformation studies in which a genotoxic initiating agent and a non-genotoxic promoting agent act synergistically to induce transformation of rodent cells. Aberrant control of gap junctional intercellular communication (GJIC) in cell transformation and carcinogenesis is well documented. Possible genotoxic as well as non-genotoxic mechanisms involved in abnormal gap junction communication control in multistage carcinogenesis are discussed.

Animals↗
PubMed2006

MX, a by-product of water chlorination, lacks in vivo genotoxicity in gpt delta mice but inhibits gap junctional intercellular communication in rat WB cells.

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a by-product of water chlorination, is a potent bacterial mutagen and rat carcinogen. In the present study, the in vivo mutagenicity, cell proliferative activity, and carcinogenicity of MX were investigated in gpt delta mice. Groups of 5 male and female 7-week-old gpt delta C57BL/6J transgenic mice were given MX at doses of 0, 10, 30, or 100 ppm in their drinking water for 12 weeks, and then killed to assess in vivo mutagenicity using 6-thioguanine and Spi- selection, and cell proliferative activity using immunohistochemistry for proliferating cell nuclear antigen (PCNA). Further groups of 10 male and female gpt delta mice were given 0 or 100 ppm MX for 78 weeks, and a full necropsy with histopathological examination of all organs was conducted to detect neoplastic lesions. The 12-week MX treatment did not result in mutagenicity in the livers or lungs or cell proliferative activity in several organs of the mice, and the 78-week treatment did not cause carcinogenicity. Additional investigations were conducted to evaluate the potential of MX to inhibit gap junctional intercellular communication (GJIC) in rat liver epithelial cells (WB cells) by the scrape loading/dye transfer method. Inhibition of GJIC was detected within 2 hr with a noncytotoxic dose of MX (4 microg/ml), followed by partial restoration after 5 hr. A second phase of inhibition occurred after 10 hr and then the lowered level persisted for the 24 hr-incubation period. Dose-dependent inhibition was evident at both 2 hr and 24 hr, with much stronger effects at the former time. These findings indicate that MX is not mutagenic, mitogenic or carcinogenic in mice, and suggest that the compound exerts epigenetic actions leading to GJIC inhibition.

Animals↗
PubMed2001

Role of stem cells and gap junctional intercellular communication in human carcinogenesis.

Epidemiological data, experimental animal bioassays, studies of in vitro neoplastic transformation, and molecular oncology studies have implicated a multistage, multimechanism process in human carcinogenesis. From animal carcinogenesis studies, the operational concept of a single normal cell being irreversibly altered during the first step in carcinogenesis is called initiation. The subsequent interruptible or reversible clonal expansion of these initiated cells by non-cytotoxic mitogenic stimuli, compensatory hyperplasia due to cell death by necrosis, or inhibition of apoptosis is referred to as the promotion phase. Last, when one of these clonally expanded, initiated cells acquires sufficient genetic/epigenetic alterations to become neoplastically transformed and acquire the phenotypes of promoter independence, invasiveness and metastasis, it is referred to as the progression step of carcinogenesis. This report hypothesizes that the single normal cell that is initiated is a pluripotent stem cell. By assuming that the normal pluripotent stem cell is immortal and becomes mortal when induced to terminally differentiate, initiation would be viewed as the irreversible process by which a stable alteration in a finite number of proto-oncogenes and/or tumor suppressor genes could block terminal differentiation or "mortalization". Promotion would involve the reversible inhibition of gap junctional intercellular communication (GJIC) and while progression occurs with the stable down-regulation of GJIC.

Animals↗
PubMed1998

Involvement of oxidative stress in motorcycle exhaust particle-induced DNA damage and inhibition of intercellular communication.

In this study, we investigated the involvement of reactive oxygen species (ROS) in the motorcycle exhaust particle (MEP)-induced genotoxic and non-genotoxic activity in mammalian cell systems. Initially, the capability of MEP to induce ROS was evaluated by using 2',7'-dichlorofluorescin diacetate (DCFH-DA) to detect hydrogen peroxide (H2O2). A five-fold increase in H2O2 was observed in Chinese hamster lung V79 and human lung carcinoma Calu-1 cells treated with 100 microg/ml MEP for 2 h. Under the same experimental conditions, only a two-fold elevation in H2O2 was detected in hepatic cell systems such as BNL.Cl.2, HepG2, and Hep3B. Treatment of the V79 cells with varying concentrations of MEP caused a dose-dependent increase in sister chromatid exchanges (SCEs), which are effectively inhibited by addition of antioxidants, N-acetyl-l-cysteine (NAC) and ascorbic acid. Furthermore, we determined the oxidized bases in the V79 cells after exposure to MEP. The result showed that 500 microg/ml MEP induced a 3.7-fold increase in thymine glycol (TG) and a seven-fold increase in 8-hydroxy-guanosine (8-OHGua) as compared to untreated cells. We subsequently examined whether MEP would affect gap junctional intercellular communication (GJIC), a tumor promotion process, in V79 cells. We found that MEP inhibited GJIC in a dose-response fashion. Maximal inhibition occurred at 500 microg/ml. The concentration that inhibited at 0.5 of the fraction of the control was 200 microg/ml. Interestingly, when cells were pretreated with NAC or ascorbic acid, they could abolish the MEP-mediated inhibition of GJIC. In addition, a moderate decrease of glutathione was observed in the V79 cells during exposure to MEP. Taken together, our findings suggest that MEP can induce oxidative stress in a broad range of cell lines, especially in lung cell systems. The MEP-induced oxidative stress was critically involved in both genotoxic and non-genotoxic activity.

Animals↗
PubMed1996

Steroid hormone effects on intercellular communication between term pregnant human myometrial cells before labor.

The appearance of gap junctions (GJs) between myometrial smooth muscle cells is one of the major events associated with the onset of labor. We have employed dye-coupling and electrical-current injection techniques to study the mechanisms by which steroid hormones regulate GJs in term pregnant myometrium of women before labor. Progesterone (P4) did not alter the input resistance (Ro) of the tissues when added to Tyrode's solution, which was used as control treatment. Octanol, the putative gap junctional uncoupling agent, increased the Ro of the cells compared to the control and P4-treated groups. The membrane potential (Em) did not differ between these groups. However, when P4 was applied after the tissue was perfused with estradiol (E2), the results changed dramatically: the Em hyperpolarized, and the Ro increased. Octanol increased the Ro in E2-treated tissues, but did not affect the Em. Consecutive application of E2, octanol, E2, and P4 resulted in rapid changes in the Ro of the cells. Dye-coupling was mostly detected between cells from controls and E2-treated tissues. These results indicate that P4 exerts its effects in the presence of E2 and that P4 has rapid effects on the intercellular communication between human myometrial cells.

Cell Communication↗
PubMed2006

The expression of multiple connexins throughout spermatogenesis in the rainbow trout testis suggests a role for complex intercellular communication.

Certain fish, such as rainbow trout (Oncorhynchus mykiss), are seasonal breeders. Spermatogenesis in rainbow trout is synchronous; therefore, at any time point during this process, germ cells are predominantly at the same stage of development. As such, rainbow trout represent an excellent model in which to study spermatogenesis. Gap junctions are composed of connexons, which are themselves formed by six transmembrane proteins termed connexins (Cxs). The objectives of this study were to assess which Cxs are expressed in the rainbow trout testis, and if their expression was stage specific during gonadal maturation. Rainbow trout were killed at various stages of maturation, and total cellular RNA was isolated from the testes. RT-PCR using degenerate primers recognizing all vertebrate Cxs indicates that there are several different Cxs in trout testes. Amplicons were cloned and sequenced. Homology comparisons indicate that these were cx43, cx43.4, cx31, and cx30. Immunolocalization of these Cxs indicate that Cx43 was localized primarily to Sertoli cells, while Cx43.4 was localized along the lateral plasma membranes between adjacent spermatocytes. Cx30 was localized to the interstitial Leydig cells, and Cx31 was localized primarily to the endothelium of interstitial blood vessels. The expression of each Cx varied as a function of the stage of spermatogenesis, suggesting that the expression of these proteins is highly regulated. Together, these results indicate that intercellular communication in the testis is complex, involves several different Cxs, and is a highly regulated process.

Amino Acid Sequence↗
PubMed1986

Characterization of luteinizing hormone-releasing hormone receptor binding in rat pituitary cell monolayer cultures; influence of intercellular communication.

Receptors for the luteinizing hormone-releasing hormone (LHRH) were characterized in rat pituitary cells cultured for 3 days as monolayers on coverslips using 125I-[D-Ala6-Pro9-LHRH-NEt] as the labeled ligand. The monolayers were left intact during the binding assay. Specific binding displayed the various characteristics of binding to the physiological LHRH receptor. Various kinetic data corresponded to those reported previously. However, in these cultured cells, in which binding was tested in a physiological medium, the dose response of competition for binding by LHRH agonists ranged over a smaller concentration range (less than 2 orders of magnitude) than that by LHRH antagonists. In a cation-free buffer competition curves of agonists and antagonists were parallel but the apparent dissociation constant was lower than in the physiological medium. In cultures of pituitary cell populations separated by unit gravity sedimentation, the specific binding increased with the proportional number of gonadotrophs in the various populations. However, when the gonadotroph-richest population (approximately equal to 70% gonadotrophs) was cultured after recombination with gonadotroph-poor populations, binding capacity significantly increased. Microscopic examinations suggested that this phenomenon was the consequence of disrupting cellular contacts among gonadotrophs. It is concluded that certain characteristics of LHRH receptors tested on cells in a tissue-like organization and in a physiological environment are different from those reported previously in disrupted cells or monodispersed cell suspensions and that intercellular communication is an important factor controlling LHRH receptors.

Animals↗
PubMed2004

Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes.

BACKGROUND: Bone marrow stromal cells (BMSCs) have the potential to differentiate into various cells and can transdifferentiate into myocytes if an appropriate cellular environment is provided. However, the molecular signals that underlie this process are not fully understood. In this study, we show that BMSC differentiation is dependent on communication with cells in their microenvironment. METHODS AND RESULTS: BMSCs were isolated from green fluorescent protein (GFP)-transgenic mice and cocultured with myocytes in a ratio of 1:40. Myocytes were obtained from neonatal rat ventricles. The differentiation of BMSCs in coculture was confirmed by immunohistochemistry, electron microscopy, and reverse transcription-polymerase chain reaction. Before coculturing, the BMSCs were negative for alpha-actinin and exhibited a nucleus with many nucleoli. After 7-day coculture with myocytes, some BMSCs became alpha-actinin-positive and formed gap junctions with native myocytes. However, BMSCs separated from myocytes by a semipermeable membrane were still negative for alpha-actinin. Transdifferentiated myocytes from BMSCs were microdissected from cocultures by laser captured microdissection to determine the changes in gene expression. BMSCs cocultured with myocytes expressed mouse cardiac transcription factor GATA-4. CONCLUSIONS: When cocultured with myocytes, BMSCs can transdifferentiate into cells with a cardiac phenotype. Differentiated myocytes express cardiac transcription factors GATA-4 and myocyte enhancer factor-2. The transdifferentiation processes rely on intercellular communication of BMSCs with myocytes.

Animals↗
PubMed2001

Suppressed gap junctional intercellular communication in carcinogenesis of endometrium.

To examine whether and at which stage of endometrial carcinogenesis decreased connexin expression occurs, we investigated changes in the expression of the gap junction proteins, connexin 26 (Cx26), Cx32 and Cx43, in human endometrial hyperplasia and cancer samples. Forty-eight endometrial tissue samples (15 endometrial hyperplasias and 33 endometrial cancers) were subjected to immunofluorescence and RT-PCR analysis. In endometrial hyperplasia, Cx26 was aberrantly expressed in all samples as revealed immunohistochemically. There was weak or negative expression in 12 samples (80.0%) and diffuse expression in cytoplasm in 3 samples (20.0%). Cx32 expression in those samples was similar to that of Cx26; there was weak or negative expression in 11 samples (73.3%) and diffuse expression in 4 samples (26.7%). In endometrial cancer, Cx26 was expressed weakly or negatively in 25 samples (75.8%), diffusely in 6 samples (18.2%) and normally in 2 samples (6.1%), while Cx32 was expressed weakly or negatively in 26 samples (78.8%), diffusely in 5 samples (15.2%) and normally in 2 samples (6.1%). It was confirmed that weak staining of Cx26 and Cx32 was due to poor expression of their mRNA. All samples showed weak Cx43 protein expression as revealed by immunohistochemical analysis. In the majority of samples, concomitant expression levels of Cx26 and Cx32 protein were observed, confirming our long-term hypothesis that Cx26 and Cx32 are both abnormally regulated in a coordinated fashion in the endometrium. Our results indicate that during endometrial carcinogenesis, loss of gap junctional intercellular communication (GJIC) may occur due to the suppressed expression and the aberrant localization of connexin at relatively early stages.

Adenocarcinoma↗
PubMed2004

Glucagon increases gap junctional intercellular communication via cAMP in the isolated perfused rat liver.

The effects of glucagon on the subacinar distribution of hepatic transmembrane potentials were studied in the perfused fasted rat liver. The livers were perfused with a Krebs-Henseleit buffer, and membrane potentials of matched periportal and pericentral hepatocytes were determined using glass microelectrodes. Lactate- and pyruvate-induced glucose production and O2 uptake were potentiated by 10(-8) M glucagon. Twenty-five micromoles 8-bromoadenosine 3',5'cyclic monophosphate (8-BrcAMP) exhibited stimulatory effects similar, in terms of glucose production and O2 uptake to those of glucagon. Octanol (0.1 and 0.5 mM) had no effect on glucose production but reversibly increased O2 uptake by 16% to 30% over all experiments. Under basal conditions (no exogenous substrate) hepatocyte membrane potentials averaged approximately -27 mV, and no gradients were found between periportal and pericentral hepatocytes. Addition of lactate and pyruvate produced hyperpolarization in all hepatocytes. However, there was a small but statistically significant gradient produced across the hepatic acinus in membrane potential, i.e., the hyperpolarization was higher in the periportal region compared with the pericentral region. Glucagon and 8-BrcAMP induced marked hyperpolarization in periportal and pericentral hepatocytes with no gradients across the acinus. Although no changes were found under basal and lactate plus pyruvate, 0.5 mM octanol induced heterogeneity of membrane potential during glucagon and 8-BrcAMP stimulation. Our findings suggest that glucagon-induced homogeneity of membrane potential may be mediated by increased gap junctional coupling. In addition, cAMP may be responsible for the increase in the intercellular communication during glucagon stimulation.

8-Bromo Cyclic Adenosine Monophosphate↗