• BMB Reports
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• v.36 no.1
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• pp.43-48
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• 2003

Understanding the process of carcinogenesis will involve both the accumulation of many scientific facts derived from molecular, biochemical, cellular, physiological, whole animal experiments and epidemiological studies, as well as from conceptual understanding as to how to order and integrate those facts. From decades of cancer research, a number of the "hallmarks of cancer" have been identified, as well as their attendant concepts, including oncogenes, tumor suppressor genes, cell cycle biochemistry, hypotheses of metastasis, angiogenesis, etc. While all these "hallmarks" are well known, two important concepts, with their associated scientific observations, have been generally ignored by many in the cancer research field. The objective of the short review is to highlight the concept of the role of human adult pluri-potent stem cells as "target cells" for the carcinogenic process and the concept of the role of gap junctional intercellular communication in the multi-stage, multi-mechanism process of carcinogenesis. With these two concepts, an attempt has been made to integrate the other well-known concepts, such as the multi-stage, multi-mechanisn or the "initiation/promotion/progression" hypothesis; the stem cell theory of carcinogenesis; the oncogene/tumor suppression theory and the mutation/epigenetic theories of carcinogenesis. This new "integrative" theory tries to explain the well-known "hallmarks" of cancers, including the observation that cancer cells lack either heterologous or homologous gap junctional intercellular communication whereas normal human adult stem cells do not have expressed or functional gap junctional intercellular communication. On the other hand, their normal differentiated, non-stem cell derivatives do express connexins and express gap junctional intercellular communication during their differentiation. Examination of the roles of chemical tumor promoters, oncogenes, connexin knock-out mice and roles of genetically-engineered tumor and normal cells with connexin and anti-sense connexin genes, respectively, seems to provide evidence which is consistent with the roles of both stem cells and gap junctional communication playing a major role in carcinogenesis. The integrative hypothesis provides new strategies for chemoprevention and chemotherapy which focuses on modulating connexin gene expression or gap junctional intercellular communication in the premalignant and malignant cells, respectively.

• Biomolecules & Therapeutics
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• v.11 no.4
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• pp.224-231
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• 2003

The aim of this study was to investigate the effect of resveratrol on the oxidative stress-induced inhibition of gap junctional intercellular communication in HaCaT keratinocytes. Anti-oxidative activity of resveratrol was measured by $\alpha,\alpha$-diphenyl-$\beta$-picrylhydrazyl assay and dichlorodihydrofluorescein diacetate oxidation assay. Gap junctional intercellular communication in HaCaT keratinocytes was assessed using the scrape loading/dye transfer technique. Western blots and reverse transcription-polymerase chain reaction were also analyzed for connexin 43 protein and mRNA expression, respectively. Resveratrol scavenged directly the stable $\alpha,\alpha$-diphenyl-$\beta$-picrylhydrazyl radical over a concentration range of 4 mg/ml ($78.2{\pm}2.7$% of control) to 500 mg/ml ($29.9{\pm}4.2$% of control) and decreased the intracellular reactive oxygen species induced by ultraviolet A (UVA) irradiation ($89.3{\pm}1.1$% of UVA group), ultraviolet B (UVB) irradiation ($70.9{\pm}1.7$% of UVB group) and 12-0-tet-radecanoylphorbol-13-acetate (TPA, $48.3{\pm}1.1$% of TPA group), respectively. UVA irradiation and TPA markedly reduced gap junctional intercellular communication, which was restored by resveratrol. There were no significant differences in the level of connexin 43 protein and mRNA expression among any of the experimental groups. Our data suggests that resveratrol has the protective effect on the oxidative stress-induced inhibition of gap junctional intercellular communication in HaCaT keratinocytes, and this protection is likely due to the scavenging of reactive oxygen species.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.289-298
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• 2023

Complex diseases including cardiovascular disease are caused by a combination of the alternation of many genes and the influence of environments. Recently, non-coding RNAs (ncRNAs) have been shown to be involved in diverse diseases, and the functions of various ncRNAs have been reported. Many researchers have elucidated the mechanisms of action of these ncRNAs at the cellular level prior to in vivo and clinical studies of the diseases. Due to the characteristics of complex diseases involving intercellular crosstalk, it is important to study communication between multiple cells. However, there is a lack of literature summarizing and discussing studies of ncRNAs involved in intercellular crosstalk in cardiovascular diseases. Therefore, this review summarizes recent discoveries in the functional mechanisms of intercellular crosstalk involving ncRNAs, including microRNAs, long non-coding RNAs, and circular RNAs. In addition, the pathophysiological role of ncRNAs in this communication is extensively discussed in various cardiovascular diseases.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.123-123
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• 2003

Primary cultures of rat fetus brain exhibit phenotypes of neuron, oligodendrocyte, and astrocyte from "neurospheres". To understand the role of mitogen-activated protein kinase (MAPK) cascade and gap junctional intercellular communication (GJIC) in the differentiation of neurosphere-derived astrocyte, we investigated the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the cultured astrocyte morphology.(omitted)

• The Plant Pathology Journal
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• v.21 no.1
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• pp.21-26
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• 2005

Homeotic proteins have pivotal roles during the development of both plant and animals. Many homeotic proteins exert control over cell fate in cells where their genes are not expressed, i.e., in a non-cell autonomous manner. Cell-to-cell communication, which delivers critical information for position-dependent specification of cell fate, is an essential biological process in multicellular organisms. In plants, there are two pathways for intercellular communication that have been identified: the ligand/receptor-mediated apoplastic pathway and the plasmodesmata-mediated symplasmic pathway. Regulatory proteins and RNAs traffic symplasmically via plasmodesmata and play a critical role in intercellular communication. Thus, the non-cell autonomous function of homeotic proteins can be explained by the recent discovery of cell-to-cell trafficking of proteins or RNAs. This article specifically focuses on understanding the intercellular movement of homeodomain proteins, a family of homeotic proteins.

• Journal of Korean Society for Atmospheric Environment
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• v.13 no.3
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• pp.207-214
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• 1997

We collected airborne complex mixtures in a industrial area of Yeochun, and examined whether these complex mixtures could affect gap junctional intercellular communication (GJIC) in a cultured WBF-344 rat liver epithelial cells (LEC). Since the reduction of GJIC plays an important role in chemical carcinogenesis, measurement of changes of GJIC is a meaningful method to screen carcinogenicity of these mixtures. High and low volume samples were dissolved in dimethyl sulfoxide (DMSO) and tested. Blank filter extractions were also examined for exclud-ing possible toxicity of filter itself, and TPA (12-O-tetradecanoylphorbol-13-acetate) and DMSO were used as positive and negative control, respectively. When the cells were exposed to samples at concentration below that required to maintain rather than 85% cell viability based on the result of neutral red uptake assay, maximal inhibition of GJIC was observed at 1hr after treatment with both high and low volume samples by scrape-loading dye transfer assay. In fluorescence recovery after photobleaching assay, recovery rates via gap junctions were 33%/min in high volume sample and 62%/min in low volume sample. In together, airborne samples collected in Yeochun inhibited GJIC in a cultured WBF-344 rat LEC. These results suggest airborne samples tested in this experiment may attribute to cause a certain type and degree of cancers in in vivo when exposured for some periods.

• Korean Journal of Food Science and Technology
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• v.39 no.5
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• pp.558-563
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• 2007

This study was conducted to analyze the cytotoxic effects of butylated hydroxytoluene (BHT) and propyl gallate (PG) in WB-F344 rat liver epithelial cells. Here we measured the inhibition level of gap junctional intercellular communication (GJIC) and elucidated the relationships between GJIC and mitogen-activated protein kinases (MAPKs) such as ERK, JNK, and p38. The cytotoxicities of BHT and PG appeared at concentrations of 1.0mM and 0.25mM, respectively, in the WB-F344 cells; and GJIC inhibition, which was analyzed by a scrape-loading/dye transfer assay and Western blotting analysis, appeared at 0.6mM for BHT and 0.1mM for PG, respectively. Also, the phosphorylations of Cx43, ERK, JNK, and p38 increased in dose-dependent manners. This suggests that BHT and PG treatments inhibited GJIC by the phosphorylation of MAPKs prior to cell damage.

• Journal of Food Hygiene and Safety
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• v.16 no.3
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• pp.212-220
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• 2001

To investigate the modifying effect of Kwao Kreu, Pueraria mirifica (PM), we performed two kind of studies which are the non-surgical medium-term carcinogenicity study and the modulation of gap junctional intercellular communication study. The first study, a non-surgical medium-term carcinogenicity bioassay was done to investigate the modifying effect of Kwao Keru, Pueyaria mirifca (PH), a rejuvenating folk medicine from Thailand, on the male F344 rat liver. Specific pathogen free, male 6-week-old F3444 rats were divided into ten groups. To induce hepatocarcinogenesis, those in all groups were given a single i.p. injection of DEN (200 mg/kg) and were received two i.p. injection of DGA (300 mg/kg) at the ends of weeks 2 and 5. Rats of group 3-6 were given sodium phenobarbital (PB 0.05% in drink). A diet containing 10 mg/kg PM was given to group 2 during the post-initiation phase and to groups 4 and 5 during promotion and initiation phase, respectively. Group 6 was given the experimental diet alone throughout the experiment (8 weeks). Rats of group 7, 8, 9 and 10 were fed 1000 mg/kg PH in the same manner as group 2, 4, 5 and 6. All animals were sacrificed at 8 weeks after DEN administration. Result of the immunohistochemical staining of the glutathione S-transferase placental form (GST-p) indicated that the numbers and areas of the preneoplastic leisions were not significantly changed in all PM treatment group comparing to control group. Also the numbers and areas of GST-p positive foci among group 7, 8, 9 and 10 were not significantly changed in comparing to control group. To study the effect of PM on the modulation of gap junctional intercellular communication, the present study was performed scrape-loading dye transfer (SL/DT) assay in human keratinocytes. The results showed that PM could not modulate GJIC. These results indicate that Pueraria mirifica may have no carcinogenic effects on experimental hepatocarcinogenesis in rats and gap junctional intercellular communication in human keratinocyte.

• Journal of Plant Biotechnology
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• v.34 no.2
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• pp.129-137
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• 2007

Intercellular signaling is a crucial biological process for the coordination of cell differentiation, organ development and whole plant physiology. The intercellular movement of macromolecule signals such as proteins and RNAs has emerged as a novel mechanism of cell-to-cell communication in plant. Plasmodesmata, which are intercellular symplasmic channels, provide a key pathway for cell-to-cell trafficking of regulatory proteins / RNAs. This review specifically focuses on integrating the recent understanding on non-cell autonomous macromolecules, their function and regulatory mechanisms of intercellular trafficking through plasmodesmata.

• 한국전자현미경학회:학술대회논문집
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• 2003.05a
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• pp.15-16
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• 2003