Altered function, localization and phosphorylation of gap junctions in rat liver epithelial, IAR 20, cells after treatment with PCBs or TCDD

Cell membrane‐related toxic responses and disruption of intercellular communication in PCB mechanisms of toxicity: A review

“…The authors found that gap junction Cx43 and cyclin‐dependent kinase inhibitor P27kip1 mRNA expression were significantly reduced after PCB 153 treatment. A reduced Cx43 mRNA level was also noted by Bager, Lindebro, Martel, Chaumontet and Wärngård (1997) after exposure of rat liver epithelial cells, IAR 20 to PCB 126, PCB 118 and TCDD. Interesting results were obtained by Cillo, de Eguileor, Gandolfi and Brevini (2007) with Aroclor 1,254, a mixture of PCBs (70 different PCB isomers and congeners with a molecular mass ranging from 188 to 430 Da) in rat prostate primary cultures indicating the ability of that contaminant mixture to influence mRNA stability and length of the 30‐end poly(A)tail of Cx32, Cx43 and heat shock protein 70.…”

“…PCBs disturbed regulation of gap junctional communication at several stages of the Cx “life cycle.” Sources: a Pointis, Gilleron, Carette, & Segretain, 2011; b Bager et al, 1997; c Cillo et al, 2007; d Simecková et al, 2009; e Hamers et al, 2011; f Wojciechowska et al, 2017; g Kang, Park, Ryu, & Lee, 2001. Cx, connexin; DL, “dioxin‐like”; ER, endoplasmic reticulum; ERAD, endoplasmic reticulum‐associated protein degradation; GJIC, gap junction intercellular communication; NDL, “nondioxin‐like”; PCB, polychlorinated biphenyl; PM, plasma membrane; TCDD, 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin [Colour figure can be viewed at wileyonlinelibrary.com]…”

Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression

“…Most chemical contaminants that inhibit Cx32-and/or Cx26-mediated GJIC in liver tissue do so through downregulation of the Cx mRNA and/or protein. TCDD and closely related ligands of the aryl hydrocarbon receptor (AhR), such as dioxin-like PCBs, have been reported to decrease hepatic Cx32 protein and/or mRNA levels in association with reduced levels of gap junction plaques (106,(116)(117)(118). Similar effects have been reported for a wider spectrum of chemical contaminants, including heavy metals, lipopolysaccharide, carbon tetrachloride and hexachlorobenzene (119)(120)(121)(122).…”

“…Indeed, numerous carcinogenic or tumor-promoting chemicals downregulate GJIC and/or connexin expression in vitro or in vivo in various experimental models. Polychlorinated biphenyls (PCBs) downregulate GJIC and/or Cx expression in a wide range of tissue and cellular models, including rodent hepatocytes, rodent liver epithelial cells, human keratinocytes and human breast epithelial cells (106)(107)(108)(109)(110). A thorough overview of chemical compounds that affect liver gap junctions has been provided in a recent review by Vinken et al (111).…”

Connexin 43, breast cancer tumor suppressor: Missed connections?

“…The organochlorine compound, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), was shown to alter phosphorylation of Cx43 and GJIC [117,118]. Studies in MCF7 breast cancer cells show that TCDD decreases GJIC and therefore, may not have the desired modulatory effect of Cx43 in breast cancer since it is potentially more preferable to restore GJIC [26].…”