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PubMed2002

Retroviral delivery of connexin genes to human breast tumor cells inhibits in vivo tumor growth by a mechanism that is independent of significant gap junctional intercellular communication.

The mechanism by which gap junction proteins, connexins, act as potent tumor suppressors remains poorly understood. In this study human breast tumor cells were found to exhibit diverse gap junction phenotypes including (a) undetectable Cx43 and no intercellular communication (HBL100); (b) low levels of Cx43 and sparse intercellular communication (MDA-MB-231); and (c) significant levels of Cx43 and moderate intercellular communication (Hs578T). Although retroviral delivery of Cx43 and Cx26 cDNAs to MDA-MB-231 cells did not achieve an expected substantial rescue of intercellular communication, overexpression of connexin genes did result in a dramatic suppression of tumor growth when connexin-expressing MDA-MB-231 cells were implanted into the mammary fat pad of nude mice. Subsequent immunolocalization studies on xenograph sections revealed only cytoplasmic stores of Cx43 and no detectable gap junctions. Moreover, DNA array and Western blot analysis demonstrated that overexpression of Cx43 or Cx26 in MDA-MB-231 cells down-regulated fibroblast growth factor receptor-3. Surprisingly, these results suggest that Cx43 and Cx26 induce their tumor-suppressing properties by a mechanism that is independent of significant gap junctional intercellular communication and possibly through the down-regulation of key genes involved in tumor growth. Moreover, our studies show that retroviruses are effective vehicles for delivering connexins to human breast tumor cells, facilitating potential gene therapy applications.

Animals↗
PubMed1988

Regulation of liver metabolism by intercellular communication.

The regulation of liver metabolism by intercellular communication was assessed by studying the effect of conditioned media of Kupffer and liver endothelial cells on protein synthesis, protein phosphorylation and glycogenolysis in parenchymal cells. Kupffer and endothelial cell-conditioned media enhanced the rate of protein synthesis of parenchymal cells by a factor of 1.7-1.9. The phosphorylation state of only three specific parenchymal cell proteins was influenced by the conditioned media. One, the MW 97,000 band appeared to be phosphorylase and it was found that in parallel with an enhancement of the activity of phosphorylase the glucose output by parenchymal cells could be stimulated. The effects of the conditioned media could be mimicked by prostaglandin E1, E2 and D2, whereas the pretreatment of non-parenchymal cells with aspirin abolished the stimulatory effect of these cells on the glucose output by parenchymal cells. The data indicate that prostaglandins from Kupffer and endothelial cells, mainly PGD2, can influence glucose release from parenchymal cells. The physiological importance of cellular communication was further assessed in a liver perfusion system. The tumor promoting phorbol ester PMA stimulated glycogenolysis in the perfused liver two-fold. This stimulation was blocked by the presence of aspirin. PMA is inactive on isolated parenchymal cells. Addition of PMA to the perfused liver appears to enhance the output of PGD2 in parallel with the stimulation of the glucose output. Addition of prostaglandin D2 itself could also stimulate the glucose output in the perfused liver. Our data indicate that the stimulation of glycogenolysis in the liver by PMA is mediated by non-parenchymal cells which produce PGD2 in response to PMA, leading subsequently to activation of the phosphorylase system in the parenchymal cells. It seems possible also that the tumor-promoting activity of PMA on liver will be mediated by a primary interaction with non-parenchymal cells. It is concluded that the occurrence of intercellular communication inside the liver in response to activation of non-parenchymal cells adds a new mechanism to the complex regulation of liver metabolism which may be relevant under normal and pathological conditions.

Animals↗
PubMed1985

Phorbol ester-mediated inhibition of intercellular communication in BALB/c 3T3 cells: relationship to enhancement of cell transformation.

Tumor-promoting phorbol esters reversibly inhibit intercellular communication between BALB/c 3T3 cells. In order to study the possible role of blocked intercellular communication in the promotion step in cell transformation, we investigated the effect of phorbol ester tumor promoters on cell transformation and intercellular communication in BALB/c 3T3 A31-1-1 cells by a dye-transfer method. When the cells are in the growing phase, inhibition of dye transfer by phorbol esters is complete but transient; more than 90% inhibition was observed 4 h after treatment of the cells with either 12-O-tetradecanoylphorbol-13-acetate or phorbol-12,13-didecanoate, but the extent of dye transfer returned to the control level after 24 h of treatment. However, when these phorbol ester-treated cells were cultured beyond confluence in the presence of tumor promoters, the capacity to transfer dye decreased again and was inhibited continuously for at least 5 weeks of culture. In control cultures, the extent of dye transfer between cells did not decrease at their confluence. The ability of 12-O-tetradecanoylphorbol-13-acetate and phorbol-12,13-didecanoate to induce continuous inhibition of dye transfer between these cells correlated well with their capacity to promote transformation of BALB/c 3T3 cells initiated with 20-methylcholanthrene. These results suggest that the continuously blocked intercellular communication after confluence, rather than its transient inhibition during the growing phase, might play an important role in the promotion of in-vitro two-stage transformation of BALB/c 3T3 cells.

Animals↗
PubMed1988

Further evidence for the involvement of gap-junctional intercellular communication in induction and maintenance of transformed foci in BALB/c 3T3 cells.

In order to investigate further the role of gap-junctional intercellular communication in the process of cell transformation, we examined the effects of chemicals that modulate gap-junctional communication on the induction and maintenance of transformed foci in BALB/c 3T3 cells. When dibutyryl cyclic AMP, retinoic acid, fluocinolone acetonide, or dexamethasone was added during the induction of cell transformation by standard (3-methylcholanthrene alone) or two-stage (low dose of 3-methylcholanthrene plus phorbol ester) protocols, there was a significant decrease in the number of transformed foci. When BALB/c 3T3 cells are transformed, there is selective intercellular communication between transformed and between surrounding nontransformed cells: transformed cells communicate among themselves but not with surrounding normal cells. Addition of dibutyryl cyclic AMP, retinoic acid, fluocinolone acetonide, or dexamethasone to culture dishes in which transformed foci were present induced communication between transformed cells and surrounding normal cells. In the continuous presence of these chemicals, there was a clear decrease in the number of transformed foci. These chemicals therefore appear capable of reestablishing intercellular communication between transformed and nontransformed cells and of diminishing the number of transformed foci. However, when transformed cells were isolated and placed in culture dishes at clonal density in the presence of these chemicals, there was hardly any decrease in the number of transformed colonies, suggesting that the chemicals cannot revert the phenotype of transformed cells in the absence of normal cells. These results suggest that chemicals that modulate intercellular communication not only inhibit the induction of transformed foci but also revert transformed cells to the normal phenotypes by establishing intercellular communication with surrounding normal cells.

Animals↗
PubMed1994

Gap junction-mediated intercellular communication in primary cultures of rainbow trout hepatocytes.

Gap junction-mediated intercellular communication was evaluated in primary cultures of rainbow trout hepatocytes by measurement of dye coupling. Donor hepatocytes were microinjected with fluorescent Lucifer yellow CH dye and visualization of dye spread (dye coupling) to adjacent hepatocytes was recorded. A maximum level was reached between 8 and 12 hr which was maintained up to 24 hr. Dye coupling then decreased over the next 48 hr. Cell viability was monitored by the percentage of total LDH released and trypan blue exclusion at each time point. The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA), a known inhibitor of rodent hepatic intercellular communication, on gap junction-mediated intercellular communication was evaluated in 24-hr cultures. A dose-response inhibition was demonstrated with maximum inhibition observed at 3 hr of exposure.

Animals↗
PubMed1999

Genetic and epigenetic changes of intercellular communication genes during multistage carcinogenesis.

During multistage carcinogenesis, the functions of several key genes involved in cell growth control must be damaged. Such genes include not only those involved in cell cycle control of individual cells, but also those involved in the coordination of cell growth throughout a given tissue through cell-cell communication. The most intimate form of intercellular communication is mediated by gap junctions. Gap junctional intercellular communication (GJIC) is known to transfer small water soluble molecules, including cAMP and IP3, from the cytoplasm of one cell to that of its neighbors; the growth of a given GJIC-associated cell is thus kept in check by other GJIC-connected cells. Most tumor cells have a reduced ability to communicate among themselves and/or with surrounding normal cells, confirming the importance of intact GJIC in growth control. When connexin (gap junction protein) genes are transfected into such cells, normal cell growth control is often recovered. Certain dominant-negative mutant connexin genes can reverse such tumor suppression. While these results suggest that connexin genes form a family of tumor suppressor genes, so far we have found no connexin gene mutations in human tumors; only two connexin gene mutations were found in chemically induced rat tumors. On the other hand, our recent studies suggest that connexin genes may be inactivated by hypermethylation of their promoter regions, suggesting that epigenetic inactivation of connexin genes may be a mechanism of GJIC disturbance in certain tumors. However, in many tumor cells connexins are normally expressed but aberrantly localized. The mechanisms of aberrant localization of connexins include lack of an appropriate cell-cell recognition apparatus and aberrant phosphorylation of connexins. These results suggest that GJIC disorders may occur not only because of aberrant expression of connexin genes themselves, but also as a result of disruption of various control mechanisms of the protein functions.

Animals↗
PubMed1996

Inhibition of gap junction intercellular communications of cultured rat hepatocytes by ethanol: role of ethanol metabolism.

BACKGROUND/AIMS: In a previous study, we reported that in cultured rat hepatocytes, ethanol inhibits intercellular communication which is known to play a central role in the regulation of cell growth and differentiation. This work was designed to find out if ethanol exerts a direct action on cell membranes, comparable to other long-chain (C6-C9) alcohols, or an indirect action. METHODS: Intercellular communication was measured on short-term cultured rat hepatocytes by the fluorescent Lucifer-Yellow CH transfer method. Intracellular pH was measured by spectrofluorimetry and membrane expression of connexin 32 by indirect immunofluorescence. RESULTS: Under our conditions, ethanol (20 mM) inhibited intercellular communication of hepatocytes to the same extent as did octanol and 1 mM. Immunofluorescence semi-quantitative studies of connexin 32 suggested that the observed inhibition was not related to a decrease in the number of gap junction plaques. In contrast with those of octanol, the inhibitory effects of ethanol appeared to be indirect because the inhibition of ethanol metabolism by 4-methyl pyrazole abolished its effects on intercellular communication, while 4-methyl pyrazole did not influence the effects of octanol. Acetaldehyde, the main metabolite of ethanol was without effect on gap junctions. CONCLUSIONS: This suggests that the inhibition of intercellular communication induced by ethanol may be included among the consequences of intermediary cell metabolism disturbances indirectly due to ethanol oxidation. This may be one of the mechanisms by which ethanol metabolism exerts a hepatotoxic possibly carcinogenic action.

1-Octanol↗
PubMed1987

Strain and species effects on the inhibition of hepatocyte intercellular communication by liver tumor promoters.

The effect of the liver tumor promoters phenobarbital (PB), 1,1-bis(4-chlorophenyl)-2,2,2-trichlorethane (DDT), and dieldrin on gap junction-mediated intercellular communication between primary cultured hepatocytes from male mice (B6C3F1), C3H, C57BL, and Balb/c strains) and male F344 rats was determined. Intercellular communication was detected autoradiographically as the passage and incorporation of [5-3H]uridine nucleotides from prelabelled donor hepatocytes to donor-contacting recipient hepatocytes. At non-toxic concentrations, PB (20-500 micrograms/ml) inhibited intercellular communication between B6C3F1, C3H, and Balb/c mouse hepatocytes and F344 rat hepatocytes, but not between C57BL mouse hepatocytes. DDT (1-10 micrograms/ml) inhibited intercellular communication between hepatocytes from all 4 strains of mice and the F344 rat. Dieldrin (1-10 micrograms/ml) inhibited intercellular communication between hepatocytes from the 4 strains of mice but not between rat hepatocytes. These findings showed a good correlation with the in vivo liver tumor promoting/hepatocarcinogenic actions of PB, DDT and dieldrin in the 4 mouse strains and the F344 rat strain.

Animals↗
PubMed1996

Alteration of intercellular communication in a human urothelial carcinoma cell-line by tumor-promoting agents.

BACKGROUND: Most of the findings that support a good association between inhibition of intercellular communication and tumor promotion have been demonstrated by studies of animal cells, while it has been accepted that most tumor-promoting agents are specific to species and organs. Therefore, the influence of tumor-promoting agents on intercellular communication was investigated using a human urothelial cell-line. METHODS: The effects of six tumor-promoting agents, including dichlorodiphenyltrichloroethane (DDT), butylated hydroxyanisole (BHA), saccharin, cyclamic acid, phenobarbital, and DL-tryptophan, on intercellular communication in a human urothelial cell-line (JTC-30) were investigated by using a dye-transfer assay after 48- and 96-hour exposure to each agent. Cytotoxicity was determined using the colony-forming method after 48-hour and 7-day exposure to each agent. RESULTS: DDT, BHA, saccharin, and cyclamic acid inhibited intercellular communication after either 48- or 96-hour exposure at concentrations that were nontoxic to the cells after 7-day exposure. Phenobarbital and DL-tryptophan inhibited intercellular communication only at toxic concentrations. CONCLUSIONS: Since the former four agents are known to be direct tumor promoters, and the metabolites of the later two agents have been regarded as tumor promoters, the results suggest that current methodology using the JTC-30 cell-line may be applicable to the screening to detect direct tumor promoters of human urothelium.

Adult↗
PubMed1983

Role of intercellular communication in the promotion of C3H/10T1/2 cell transformation.

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) upon intercellular communication and promotion were studied in cultures of C3H/10T1/2 mouse embryo fibroblasts. Cell-to-cell communication was quantitated by autoradiographic analysis of [3H]uridine transfer from prelabelled donor cells to an excess of unlabelled recipient cells during a 4 h co-cultivation. Extensive transfer of label was observed from donor to recipient cells in contact. Treatment of non-transformed C3H/10T1/2 cultures with 250 ng/ml TPA at co-cultivation of donor and recipient cells markedly inhibited intercellular communication during the 4 h incubation, producing an 80% reduction in uridine exchange relative to solvent-treated control cultures. Concentrations of TPA ranging from 0.25 to 25 ng/ml were also effective in inhibiting [3H]uridine exchange in a dose dependent fashion from 13% to 74%. This inhibition of intercellular communication was transient; cells exposed to 250 ng/ml TPA for 1.5 h prior to co-cultivation with TPA exhibited a 60% inhibition and the exchange of uridine had increased to control values in cultures pretreated for 12-72 h. An examination of label transfer between non-transformed and transformed C3H/10T1/2 cells indicated that both the extent of inhibition by TPA and the kinetics of communication inhibition were similar to that observed for non-transformed cells. Initiation and promotion experiments demonstrated that exposure to 250 ng/ml TPA for 5 weeks, but not to reduced concentrations of 0.25, 2.5 or 25 ng/ml, was capable of promoting morphological transformation. The lack of correlation between the dose responses of TPA for promotion and for reduction of cell-to-cell communication, and the transient nature of intercellular communication inhibition by TPA, suggests that an inhibition of cell-to-cell communication is not a sufficient event for promotion of oncogenic transformation in these cells.

Animals↗
PubMed1995

Inhibition of rat liver gap junction intercellular communication by tumor-promoting agents in vivo. Association with aberrant localization of connexin proteins.

BACKGROUND: Gap junctional intercellular communication is believed to play an important role in the maintenance of tissue homeostasis, and disruption of it has been proposed to be involved in carcinogenesis. A number of tumor-promoting agents have been shown to inhibit capacity for intercellular communication in cell culture studies. Recently, we developed a simple dye-transfer technique to evaluate cell-coupling function in fresh liver slices, and we used it to show that inhibition of intercellular communication is associated with rat liver tumor progression. Using this method with analysis of gap junction protein connexin expression, we have examined whether and how different liver-specific tumor-promoting agents inhibit dye-coupling in rat liver in vivo. EXPERIMENTAL DESIGN: Groups of Fischer 344 rats received repeated chronic treatment of phenobarbital (PB), polychlorinated biphenyls (PCB), dichlorodiphenyltrichloroethane (DDT), and clofibrate (CF) for 5 weeks. After 1, 2, and 5 weeks of treatment, intercellular communication via gap junctions was evaluated by the dye-transfer assay in liver slices taken immediately after killing the rats. In parallel, the expression of connexins (cx) 32, 26, and 43 (gap junction proteins expressed in the liver) was studied at the mRNA and protein levels. RESULTS: All four tumor-promoting agents decreased dye-coupling in rat liver. This decrease was associated with a reduced number of gap junctions and aberrant localization of some amount of cx 32 proteins in hepatocytes; cx 32 often was observed in the cytoplasm of hepatocytes instead of at gap junctions in the plasma membrane. Western blot analysis showed only slight changes in the level of cx 32 proteins. Although cx 26 proteins at gap junctions were usually decreased by tumor promoters in rat liver, local induction of cx 26 protein expression in centrolobular groups of hepatocytes after PCB and DDT treatment was observed. The expression of cx 43 was induced in hepatocytes after PCB, DDT, and CF exposure, but this protein was also localized intracytoplasmically, suggesting no functional role. All four tested tumor-promoting agents also increased cell proliferation, as revealed by staining with an anti-Ki 67 antibody. CONCLUSION: The results demonstrate that different types of liver tumor-promoting agents inhibit dye-coupling in rat liver in vivo. This inhibition may be due to aberrant localization of the major liver gap junction protein cx 32, rather than its transcriptional or translational disregulation.

Animals↗
PubMed1994

Effect of lipids and aldehydes on gap-junctional intercellular communication between human smooth muscle cells.

Inhibition of intercellular communication is an important feature in the tumour promotion phase of a multistage carcinogenesis model. In atherosclerosis inhibition of cell-cell communication by atherogenic compounds, e.g., low density lipoproteins (LDL), also seems to be important. For testing atherogenic compounds we used an atherosclerosis relevant cell type, namely human smooth muscle cells. In order to investigate which part of the LDL particle would be involved in inhibition of metabolic co-operation between human smooth muscle cells in culture we tested several fatty acids and their breakdown products, namely aldehydes. Unsaturated C-18 fatty acids markedly influenced gap-junctional intercellular communication (GJIC), whereas saturated (C18:0, C16:0) and unsaturated fatty acids with > 20 carbon atoms did not inhibit GJIC. In the case of oleic and elaidic acid, orientation seemed important; however, after exposure to palmitoleic and palmitelaidic acid no differences were found. The most potent inhibitor of GJIC was linoleic acid, which inhibited GJIC by 75%. No correlation was found between degrees of unsaturation and ability to inhibit GJIC. Of the tested aldehydes, hexanal, propanal, butanal and 4-hydroxynonenal did significantly inhibit GJIC, while pentanal had no effect. Since modification of LDL was shown to be important in order for LDL to inhibit GJIC, these results show that fatty acids and their oxidative breakdown products may be of importance for the inhibition of GJIC by LDL.

Aldehydes↗
PubMed2000

[Studies on intercellular communication of rabbit lens epithelial cells in vitro].

OBJECTIVE: To investigate the intercellular communication in rabbit lens epithelial cells and effect of dexamethasone and heparin on it. METHODS: Rabbit lens epithelial cells were cultured and exposed to different concentrations of dexamethasone (10, 100, 300 mg/L), heparin (1 x 10(5), 2 x 10(5), 4 x 10(5) U/L) for 48 hours at 37 degrees C. The fluorescence redistribution after photobleaching (FRAP) was used for the analysis. The mean fluorescence recovery rate (MFRR, %/min) of the cells labelled with 6-carboxy fluorescein diacetate (CFDA) after photobleaching was measured with laser scanning cytometry ACAS Ultima. RESULTS: MFRR (%/min) of the cells after exposure to dexamethasone was 0.375 +/- 0.236 in the control group, 0.491 +/- 0.239 in the group of dexamethasone 10 mg/L, 0.996 +/- 0.447 in the group of dexamethasone 100 mg/L, 0.984 +/- 0.379 in the group of dexamethasone 300 mg/L, respectively (F = 26.07, P < 0.05). The MFRR after exposure of heparin was 0.375 +/- 0.236 in the control group, 0.694 +/- 0.491 in the group of heparin 1 x 10(5) U/L, 1.097 +/- 0.504 in the group of heparin 2 x 10(5) U/L, 1.082 +/- 0.501 in the group of heparin 4 x 10(5) U/L, respectively (F = 19.01, P < 0.05). CONCLUSION: It is discovered that there is intercellular communication in rabbit lens epithelial cells with FRAP analysis. Dexamethasone and heparin can enhance the intercellular communication of rabbit lens epithelial cells in dose dependent manner.

Animals↗
PubMed2005

Defective gap junctional intercellular communication in the carcinogenic process.

Gap junctions are membrane structures made of intercellular channels which permit the diffusion from cytoplasm to cytoplasm of small hydrophilic molecules. Nearly 40 years ago, the loss of functional gap junctions has been described in cancer cells and led to the hypothesis that such type of intercellular communication is involved in the carcinogenesis process. From this time, a lot of data has been accumulated confirming that gap junctions are frequently decreased or absent in cancer cells whatever their tissue and species origins. Here, we review such data by insisting on the possible links existing between altered gap-junctional intercellular communication capacity (or the altered expression of their constitutive proteins, the connexins) and the stages of cancer progression in various cancer models. Then, we analyse particular aspects of the disturbance of connexin-mediated communication in cancer such as the cytoplasmic localization of connexins, the lack of heterologous communication between cancer cells and normal cells, the role of connexin gene mutations in cancer. In a separate part of the review, we also analyse the disturbance of gap-junctional intercellular communication during the late stages of cancer (invasion and metastasis processes).

Animals↗
PubMed1994

Modulation of gap junction-mediated intercellular communication in embryonic chick mesenchyme during tissue remodeling in vitro.

Gap junction-mediated intercellular communication was analyzed in a model system in which tissue necrosis and remodeling could be modulated. This in vitro system, previously used for analysis of epithelial-mesenchymal tissue interaction, was modified to permit analysis of the presence and extent of intercellular communication by monitoring intercellular transfer of the microinjected fluorescent dye, Lucifer Yellow. Light and transmission electronmicroscopy were employed to correlate the presence and degree of gap junctional communication (coupling) with tissue morphology. Digital image analysis was used to determine cell density and mitotic indices within the outgrowths of explants. Our results indicated that cell communication in outgrowths adjacent to necrotic foci within an explant was minimal or absent. Cell-coupling in outgrowths adjacent to a compartment of viable mesenchyme was significantly higher - equivalent to unseparated control cultures. A time-course study demonstrated correlation of increased levels of cell-coupling in outgrowths with the level of tissue remodeling within an explant. Our conclusions from these studies are that embryonic mesenchymal cell populations may be selectively uncoupled as a result of alterations in the microenvironment produced by a proximate impaired cell population. It is proposed that endogenous factors in the microenvironment ("wound signals"), emanating from impaired cell populations, regulate gap junction-mediated intercellular communication in adjacent viable tissue. Normal, unimpaired populations of cells surrounding an area of injury are thereby isolated from the effects of a potentially toxic environment. This could serve as a protective function in development and may represent, in a more general sense, part of the repertoire of events associated with tissue repair and remodeling.

Animals↗
PubMed1997

Elevation of protein kinase C in thyrocytes isolated from a Lewis rat model of autoimmune thyroiditis prevents assembly of immunodetectable connexin43 gap junctions and reduces intercellular communication.

In the Lewis rat model of experimental autoimmune thyroiditis (EAT), decreased immunodetectable connexin assembly into gap junctions and diminished intercellular communication are associated with the loss of thyroid function (hypothyroidism) that occurs prior to significant tissue destruction. The current study explores the hypothesis that the loss of connexin 43 (Cx43)-mediated intercellular communication in these cells is caused by upregulation of protein kinase C (pKC) activity. Thyrocytes isolated from EAT rats exhibited a 78% increase in basal pKC activity; whereas, basal protein kinase A (pKA) activity was unchanged. Increased pKC activity was a result of increased isozyme protein levels. Thyroid cells expressed pKC isozymes gamma and lambda and had elevated levels of alpha (40%), beta (30%), delta (31%), and epsilon (25%) as quantified by western blot analyses. Furthermore, modulation of pKC activity inversely altered Cx43 assembly and function in monolayer thyrocytes. For example, octoacetyl glycerol (OAG) treatment of normal thyrocyte monolayers to increase pKC activity resulted in deficient Cx43 gap junction assembly and reduced intercellular communication indistinguishable from the deficits in EAT thyrocytes. Conversely, calphostin C inhibition of pKC activity in EAT thyrocyte monolayers restored these parameters to normal. Thus, pharmacological modulations of pKC activity in cultured thyrocytes support a causal relation between the changes in pKC activity and Cx43-mediated intercellular communication. Abnormalities in autoimmune diseased thyroid tissue (eg, increased pKC) appear to contribute to reduced intercellular coordination of thyroid follicles and thereby can affect subsequent thyroid function. The persistence of target cell abnormalities in the absence of infiltrating lymphocytes and their products supports an alternative mechanism by which thyroid function can be affected that does not depend on the loss of thyroid glandular epithelium.

Animals↗
PubMed1981

Direct intercellular communication in health and disease: an overview.

Direct intercellular communication (cell to cell coupling) is a mechanism for the local transit of information between cells and supplements the endocrine and nervous systems. Electrophysiological, biochemical, histological and cell culture techniques have established the widespread existence of coupling in mammalian tissues, and the importance of the gap junction has been recognised. Information is carried in the form of ions and small molecules between cells, and sensitive apparatus exists within each cell for controlling the permeability of the junctional membrane. The system may be important in the control and co-ordination of cellular metabolism and growth in the embryo and in adult tissues. Disorders of direct intercellular communication may be important in the pathogenesis of some diseases, in particular cancer.

Cell Communication↗
PubMed1986

Antioxidant prevention of tumor promoter induced inhibition of mouse hepatocyte intercellular communication.

The liver tumor promoters, phenobarbital (20-500 micrograms/ml), lindane (1,2,3,4,5,6-hexachlorocyclohexane, gamma-isomer; 0.1-5.0 micrograms/ml), and DDT (1,1-bis[4-chlorophenyl]-2,2,2-trichloroethane; 0.5-10.0 micrograms/ml), and the hydrogen peroxide-generating enzyme, glucose oxidase (0.01-0.10 units/ml) inhibited gap junctional intercellular communication between B6C3F1 mouse hepatocytes in primary culture. Addition of the antioxidants, superoxide dismutase (100 units/ml), DPPD (N,N'-diphenyl-1,4-phenylenediamine; 25 microM), and vitamin E (DL-alpha-tocopherol acetate; 100 microM), to tumor promoter-treated cultures prevented the inhibition of hepatocyte intercellular communication. DPPD and vitamin E, prevented the inhibition of hepatocyte intercellular communication by glucose oxidase. Superoxide dismutase had no effect on the inhibition of intercellular communication caused by glucose oxidase. These results suggest that activated oxygen species are produced during liver tumor promoter treatment of cultured mouse hepatocytes and are responsible for the inhibition of mouse hepatocyte intercellular communication by the promoters.

Animals↗