Cadmium disorganises the scaffolding of gap and tight junction proteins in the hepatic cell line WIF B9

Boucherie, Sylviane; Decaëns, C.; Verbavatz, Jean‐Marc; Grosse, Brigitte; Erard, Marie; Mérola, Fabienne; Cassio, Doris; Combettes, Laurent

doi:10.1111/boc.201200092

Cited by 17 publications

(8 citation statements)

References 65 publications

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“…The effects of Cd on GJIC and Cx have been reported mainly in the liver and liver cells of animals (Boucherie et al ., ; Jeon et al ., ; Zou et al ., , b). Nevertheless, Cx expression and the effects of Cd may vary depending on the types of cells (Li et al ., ).…”

Section: Discussionmentioning

confidence: 99%

Role of connexin 43 in cadmium-induced proliferation of human prostate epithelial cells

Liu

et al. 2017

J. Appl. Toxicol.

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Connexins (Cxs), the subunits of gap junction channels, are involved in many physiological processes. Aberrant control of Cxs and gap junction intercellular communication may contribute to many diseases, including the promotion of cancer. Cd exposure is associated with increased risk of human prostate cancer and benign prostatic hyperplasia. The roles of Cxs in the effects of Cd on the prostate have, however, not been reported previously. In this study, the human prostate epithelial cell line RWPE-1 was exposed to Cd. A low dose of Cd stimulated cell proliferation along with a lower degree of gap junction intercellular communication and an elevated level of the protein Cx43. Cd exposure increased the levels of intracellular Ca and phosphorylated Cx43 at the Ser368 site. Knockdown of Cx43 using siRNA blocked Cd-induced proliferation and interfered with the Cd-induced changes in the protein levels of cyclin D1, cyclin B1, p27 (p27) and p21 (p21). The increase in Cx43 expression induced by Cd was presumably mediated by the androgen receptor, because it was abolished upon treatment with the androgen receptor antagonist, flutamide. Thus, a low dose of Cd promotes cell proliferation in RWPE-1, possibly mediated by Cx43 expression through an effect on cell cycle-associated proteins. Cx43 might be a target for prostatic diseases associated with Cd exposure. Copyright © 2017 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

Role of connexin 43 in cadmium-induced proliferation of human prostate epithelial cells

Liu

et al. 2017

J. Appl. Toxicol.

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“…Connexin gene expression and gap junction channel gating are two major mechanisms of GJIC control [5]. It is well known that the functional loss of gap junctions can result in apoptosis, necrosis and carcinogenesis [6–9] and it is also known that Cd disrupts gap junction activity in hepatocytes in vitro and in vivo [10, 11]. …”

Section: Introductionmentioning

confidence: 99%

Salidroside Protects against Cadmium-Induced Hepatotoxicity in Rats via GJIC and MAPK Pathways

Zou

Han

et al. 2015

PLoS ONE

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It is known that cadmium (Cd) induces cytotoxicity in hepatocytes; however, the underlying mechanism is unclear. Here, we studied the molecular mechanisms of Cd-induced hepatotoxicity in rat liver cells (BRL 3A) and in vivo. We observed that Cd treatment was associated with a time- and concentration-dependent decrease in the cell index (CI) of BRL 3A cells and cellular organelle ultrastructure injury in the rat liver. Meanwhile, Cd treatment resulted in the inhibition of gap junction intercellular communication (GJIC) and activation of mitogen-activated protein kinase (MAPK) pathways. Gap junction blocker 18-β-glycyrrhetinic acid (GA), administered in combination with Cd, exacerbated cytotoxic injury in BRL 3A cells; however, GA had a protective effect on healthy cells co-cultured with Cd-exposed cells in a co-culture system. Cd-induced cytotoxic injury could be attenuated by co-treatment with an extracellular signal-regulated kinase (ERK) inhibitor (U0126) and a p38 inhibitor (SB202190) but was not affected by co-treatment with a c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results indicate that ERK and p38 play critical roles in Cd-induced hepatotoxicity and mediate the function of gap junctions. Moreover, MAPKs induce changes in GJIC by controlling connexin gene expression, while GJIC has little effect on the Cd-induced activation of MAPK pathways. Collectively, our study has identified a possible mechanistic pathway of Cd-induced hepatotoxicity in vitro and in vivo, and identified the participation of GJIC and MAPK-mediated pathways in Cd-induced hepatotoxicity. Furthermore, we have shown that salidroside may be a functional chemopreventative agent that ameliorates the negative effects of Cd via GJIC and MAPK pathways.

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“…GJIC is regulated at several levels, including channel gating and connexin expression (Vinken et al, 2011). Cd is known to disrupt the function of gap junctions of hepatocytes in vitro and in vivo (Boucherie et al, 2013;Hu et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Alpha-lipoic acid protects against cadmium-induced hepatotoxicity via calcium signalling and gap junctional intercellular communication in rat hepatocytes

Zou

Han

et al. 2015

J. Toxicol. Sci.

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-This study investigated the protective effect of alpha-lipoic acid (LA) on cadmium (Cd)-induced hepatotoxicity in BRL 3A rat liver cells. We demonstrated that LA ameliorated Cd-induced cellular injury in cell viability and nuclear fragmentation in BRL 3A cells. Furthermore, LA markedly ameliorated Cd-induced gap junctional intercellular communication (GJIC) inhibition and Cx43 mRNA expression decrease, as well as disassembly of gap junctions. The gap junction blocker carbenoxolone disodium (CBX) as well as LA protected healthy cells from Cd-exposed cells in Transwell co-culture system. LA also protected BRL 3A cells against Cd-induced elevation of the intracellular concentration of free calcium ([Ca 2+ ] i ). Pretreatment with a chelater of intracellular Ca 2+ BAPTA-AM or chelater of extracellular Ca 2+ EGTA attenuated Cd-induced cytotoxicity and GJIC inhibition. CBX exacerbated the decrease in cell viability and further elevated the increase in [Ca 2+ ] i induced by Cd, whereas BAPTA-AM partly attenuated these phenomena, while EGTA had little effects. These results suggested that Cd-induced hepatotoxicity via GJIC inhibition and [Ca 2+ ] i elevation, which originates mainly from intracellular stores. GJIC inhibition has dual effects: (i) it restricts release of Ca 2+ from the cell, which exacerbates the [Ca 2+ ] i elevation and cytotoxicity induced by Cd; and (ii) it protects healthy cells from their dangerous neighbors by blocking intercellular communication. Above all, our results indicated that LA partly prevented Cd-induced cytotoxicity via GJIC and calcium signaling in BRL 3A rat liver cells.

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Cadmium disorganises the scaffolding of gap and tight junction proteins in the hepatic cell line WIF B9

Abstract: This study demonstrates in situ the changes induced by cadmium on the organisation of cell-cell junctions and points out the importance of the association Cx32/claudin 2 for the maintenance of normal hepatocyte functions.

Cited by 17 publications

References 65 publications

Role of connexin 43 in cadmium-induced proliferation of human prostate epithelial cells

Role of connexin 43 in cadmium-induced proliferation of human prostate epithelial cells

Salidroside Protects against Cadmium-Induced Hepatotoxicity in Rats via GJIC and MAPK Pathways

Alpha-lipoic acid protects against cadmium-induced hepatotoxicity via calcium signalling and gap junctional intercellular communication in rat hepatocytes

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