scholarly journals Possible Mechanisms of Mercury Toxicity and Cancer Promotion: Involvement of Gap Junction Intercellular Communications and Inflammatory Cytokines

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Roberto Zefferino ◽  
Claudia Piccoli ◽  
Nunzia Ricciardi ◽  
Rosella Scrima ◽  
Nazzareno Capitanio
Keyword(s):  
Gap Junction ◽  
Genetic Alterations ◽  
Environmental Pollutant ◽  
Tumor Promoter ◽  
Screening Methods ◽  
Chemical Agent ◽  
Present Contribution ◽  
Dna Mutation ◽  
Mediated Effects ◽  
Intercellular Communications

A number of observations indicate that heavy metals are able to alter cellular metabolic pathways through induction of a prooxidative state. Nevertheless, the outcome of heavy metal-mediated effects in the development of human diseases is debated and needs further insights. Cancer is a well-established DNA mutation-linked disease; however, epigenetic events are perhaps more important and harmful than genetic alterations. Unfortunately, we do not have reliable screening methods to assess/validate the epigenetic (promoter) effects of a physical or a chemical agent. We propose a mechanism of action whereby mercury acts as a possible promoter carcinogen. In the present contribution, we resume our previous studies on mercury tested at concentrations comparable with its occurrence as environmental pollutant. It is shown that Hg(II) elicits a prooxidative state in keratinocytes linked to inhibition of gap junction-mediated intercellular communication and proinflammatory cytokine production. These combined effects may on one hand isolate cells from tissue-specific homeostasis promoting their proliferation and on the other hand tamper the immune system defense/surveillance checkmating the whole organism. Since Hg(II) is not a mutagenic/genotoxic compound directly affecting gene expression, in a broader sense, mercury might be an example of an epigenetic tumor promoter or, further expanding this concept, a “metagenetic” effector.

Resveratrol and X rays affect gap junction intercellular communications in human glioblastoma cells

2008 ◽  
Vol 47 (8) ◽  
pp. 587-598 ◽  
Author(s):  
Stefano Leone ◽  
Mario Fiore ◽  
M. Giuliana Lauro ◽  
Samanta Pino ◽  
Tommaso Cornetta ◽  
...  
Keyword(s):  
Gap Junction ◽  
X Rays ◽  
Glioblastoma Cells ◽  
Human Glioblastoma ◽  
Human Glioblastoma Cells ◽  
Intercellular Communications ◽  
Gap Junction Intercellular Communications

scholarly journals Gap Junction Intercellular Communications Regulate NK Cell Activation and Modulate NK Cytotoxic Capacity

2013 ◽  
Vol 192 (3) ◽  
pp. 1313-1319 ◽  
Author(s):  
Andrés Tittarelli ◽  
Ariadna Mendoza-Naranjo ◽  
Marcela Farías ◽  
Israel Guerrero ◽  
Fumitaka Ihara ◽  
...  
Keyword(s):  
Gap Junction ◽  
Cell Activation ◽  
Nk Cell ◽  
Intercellular Communications ◽  
Gap Junction Intercellular Communications

scholarly journals The tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the ras oncogene modulate expression and phosphorylation of gap junction proteins.

1991 ◽  
Vol 11 (10) ◽  
pp. 5364-5371 ◽  
Author(s):  
J L Brissette ◽  
N M Kumar ◽  
N B Gilula ◽  
G P Dotto
Keyword(s):  
Gap Junction ◽  
Intercellular Communication ◽  
Molecular Mechanisms ◽  
Serine Phosphorylation ◽  
Tumor Promoter ◽  
Gap Junctional Intercellular Communication ◽  
Beta 2 ◽  
Gap Junction Proteins ◽  
Gap Junctional ◽  
Junction Proteins

Gap junctional intercellular communication is inhibited in response to tumor promoters and oncogene transformation, suggesting that loss of this function is an important step in tumor formation. To elucidate the molecular mechanisms responsible for this inhibition, we examined the expression of gap junction proteins and mRNA in mouse primary keratinocytes after treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and/or ras transformation. During normal cell growth, keratinocytes expression the alpha 1 (connexin 43) and beta 2 (connexin 26) proteins. Within 5 min of TPA treatment, the alpha 1 protein became rapidly phosphorylated on serine residues and its expression was dramatically reduced by 24 h. The beta 2 protein, after an initial increase in expression, was also significantly reduced 24 h after treatment with TPA. ras transformation caused changes similar to those induced by TPA. The alpha 1 protein underwent an increase in serine phosphorylation, although its expression declined only slightly, while beta 2 expression was greatly reduced. The effects of TPA and ras on alpha 1 expression were additive; treatment of ras-transformed cells with TPA resulted in increased alpha 1 phosphorylation, with greatly decreased protein levels, much lower than those generated by either agent alone. These data provide a likely explanation for the similar and synergistic inhibition of gap junctional intercellular communication by phorbol esters and ras.

scholarly journals Ceramide/protein phosphatase 2A axis is engaged in gap junction impairment elicited by PCB153 in liver stem-like progenitor cells

2021 ◽  
Author(s):  
Roberta Squecco ◽  
Federica Pierucci ◽  
Eglantina Idrizaj ◽  
Alessia Frati ◽  
Elena Lenci ◽  
...  
Keyword(s):  
Gap Junction ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Environmental Pollutant ◽  
Environmental Toxicants ◽  
New Findings ◽  
Voltage Dependent ◽  
Sphingosine 1 Phosphate ◽  
Phosphatase 2A ◽  
Molecular Mode

AbstractThe widespread environmental pollutant 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) is a non-dioxin-like toxicant. It is a potential carcinogen compound able to induce gap junction (GJ) intercellular communication impairment, probably the first non-genomic event leading to tumor promotion. Although PCBs have been known for many years, the molecular mode of PCB153 action is still unclear. Recent studies from our research group have shown that the toxicant elicits a transient modulation of connexin (Cx) 43-formed GJs in hepatic stem-like WB-F344 cells involving sphingosine 1-phosphate (S1P) path. Taking into account that other strictly related bioactive sphingolipids, such as ceramide (Cer), may have different effects from S1P, here we aim to clarify the signaling paths engaged by PCB153 in the control of GJs, focusing primarily on the role of Cer. Accordingly, we have achieved a combined biomolecular and electrophysiological analysis of GJs in cultured WB-F344 cells treated with PCB153 at different time points. We have found that the toxicant elicited a time-dependent regulation of GJs formed by different Cx isoforms, through a transient modulation of Cer/Cer kinase (CerK) axis and, in turn, of protein phosphatase 2A (PP2A). Our new findings demonstrate the existence of a specific molecular mechanism downstream to Cer, which distinctly affects the voltage-dependent and -independent GJs in liver stem-like cells, and open new opportunities for the identification of additional potential targets of these environmental toxicants.

scholarly journals Investigation of Genetic Alterations in Congenital Heart Diseases in Prenatal Period

2021 ◽  
Author(s):  
Emine Ikbal Atli ◽  
Engin Atli ◽  
Sinem Yalcintepe ◽  
Selma Demir ◽  
Rasime Kalkan ◽  
...  
Keyword(s):  
Congenital Heart ◽  
Chromosomal Abnormalities ◽  
Single Nucleotide Polymorphism Array ◽  
Heart Diseases ◽  
Genetic Alterations ◽  
Chromosomal Microarray ◽  
Single Nucleotide ◽  
Dna Mutation ◽  
Genetic Examination ◽  
Direct Sequence Analysis

AbstractThe prenatal diagnosis of congenital heart disease (CHD) is important because of mortality risk. The onset of CHD varies, and depending on the malformation type, the risk of aneuploidy is changed. To identify possible genetic alterations in CHD, G-banding, chromosomal microarray or if needed DNA mutation analysis and direct sequence analysis should be planned.In present study, to identify genetic alterations, cell culture, karyotype analysis, and single nucleotide polymorphism, array analyses were conducted on a total 950 samples. Interventional prenatal genetic examination was performed on 23 (2, 4%, 23/950) fetal CHD cases. Chromosomal abnormalities were detected in 5 out of 23 cases (21, 7%). Detected chromosomal abnormalities were 10q23.2 deletion, trisomy 18, 8p22.3-p23.2 deletion, 8q21.3-q24.3 duplication, 11q24.2q24.5 (9 Mb) deletion, and 8p22p12 (16.8 Mb) deletion. Our study highlights the importance of genetic testing in CHD.

scholarly journals Gap Junction Intercellular Communication Negatively Regulates Cadmium-Induced Autophagy and Inhibition of Autophagic Flux in Buffalo Rat Liver 3A Cells

2020 ◽  
Vol 11 ◽  
Author(s):  
Hui Zou ◽  
Junzhao Yuan ◽  
Yi Zhang ◽  
Tao Wang ◽  
Yan Chen ◽  
...  
Keyword(s):  
Gap Junction ◽  
Rat Liver ◽  
Intercellular Communication ◽  
Connexin 43 ◽  
Environmental Pollutant ◽  
Autophagic Flux ◽  
Dynamic Changes ◽  
Target Organs ◽  
Gap Junction Intercellular Communication ◽  
Rapid Changes

Cadmium is an important environmental pollutant that poses a serious threat to the health of humans and animals. A large number of studies have shown that the liver is one of the important target organs of cadmium. Stimulation of cells can lead to rapid changes in gap junction intercellular communication (GJIC) and autophagy. Previous studies have shown that cadmium can inhibit GJIC and induce autophagy. In order to understand the dynamic changes of GJIC and autophagy in the process of cadmium-induced hepatotoxic injury and the effects of GJIC on autophagy, a time-gradient model of cadmium cytotoxicity was established. The results showed that within 24 h of cadmium exposure, 5 μmol/L cadmium inhibited GJIC by down regulating the expression levels of connexin 43 (Cx43) and disturbing the localization of Cx43 in Buffalo rat liver 3A (BRL 3A) cells. In addition, cadmium induced autophagy and then inhibited autophagic flux in the later stage. During this process, inhibiting of GJIC could exacerbate the cytotoxic damage of cadmium and induce autophagy, but further blocked autophagic flux, promoting GJIC in order to obtain the opposite results.

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