Silver nanoparticles up-regulate Connexin43 expression and increase gap junctional intercellular communication in human lung adenocarcinoma cell line A549

Abstract

Silver nanoparticles (Ag NPs) are increasingly being used in wound dressings, medical settings, and various household products due to their unique properties and antimicrobial activity. Despite the widespread use of Ag NP products, the molecular mechanisms underlying the biological effects of Ag NPs remain unclear. Gap junctional intercellular communication (GJIC), formed by the connexin protein family, plays a critical role in the maintenance of tissue and organ homeostasis. This study was undertaken to investigate the effects of well characterized, PVP-coated Ag NPs (69 +/- 3 nm) and silver nitrate on GJIC and connexin43 (Cx43) expression in human lung adenocarcinoma cell line A549. Our results showed that Ag NPs increased GJIC in A549 cells as assayed by dye transfer method. Western blot analysis showed that incubation of cells with Ag NPs significantly increased the expression of Cx43 protein. In addition, Ag NPs up-regulated expression of Cx43 mRNA in a dose-dependent manner. Silver nitrate failed to increase GJIC and the expression of Cx43 protein. It, however, increased Cx43 mRNA expression in A549 cells. Taken together, our results provide the first evidence that Ag NPs induced the increase of GJIC activity in A549 cells through up-regulation of Cx43 protein, suggesting that Cx43 and GJIC may be one of the targets for Ag NPs biological effects.

Silver nanoparticles increase connexin43‐mediated gap junctional intercellular communication in HaCaT cells through activation of reactive oxygen species and mitogen‐activated protein kinase signal pathway

“…We observed a great increase in GJIC after AgNP treatment and this response increased with the concentration of AgNPs. This is consistent with a previous study in the human lung adenocarcinoma cell line (Deng et al, ). GJIC increases have been suggested as a chemopreventive strategy and protection against cancer development (Trosko & Chang, ).…”

“…Scientists have grappled with the ion–NP question over the past few years; however, it remains uncertain whether nano‐silver or ionic‐silver is more toxic. In our previous study, we tried to investigate GJIC and Cx43 expression in human lung adenocarcinoma cells exposed to AgNPs and its released silver ion and found that different concentrations of silver ion failed to change GJIC and the expression of Cx43, indicating the effects of AgNPs were independent of silver ion in this case (Deng et al, ).…”

“…In addition, nanoscale titanium dioxide (TiO 2 ) with different sizes could inhibit the GJIC in human lung fibroblasts, and the inhibitory effect of 25 nm nanoscale TiO 2 on GJIC was slightly higher than that of 80 nm nanoscale TiO 2 (Qi, Deng, & Guo, ). However, our previous study found that AgNPs but not silver ion could induce upregulation of Cx43 protein and mRNA expression and increased the GJIC in human lung carcinoma cells (Deng et al, ). These results showed that GJIC might be the potential target for nanomaterials to exert their biological effects, and different nanomaterials showed different effects on GJIC.…”

Molecular mechanism of silver nanoparticles in human intestinal cells

“…Similarly, an influence of silver nanoparticles on the gap junctions of A549 cells was observed by Deng et al (2010) and morphological changes due to silver nanoparticle and silver ion incubation were also observed by others (Kawata et al, 2009;Liu et al, 2010;Nowrouzi et al, 2010). Beside the cell-cell contacts, the cellmatrix contacts and the cytoskeleton were also affected, as evidenced by a regulation of the expression of b-actin and tubulin.…”

Inhibition of gap junction intercellular communication is involved in silica nanoparticles-induced H9c2 cardiomyocytes apoptosis via the mitochondrial pathway

“…45 However, one study had opposite results that silver nanoparticles could increase the GJIC in A549 cells through upregulation of Cx43 protein level, suggesting that silver nanoparticles might target GJIC and Cx43 for their biological effects. 46 In the present study, the SNPs used had a negative effect on GJIC. We found that SNPs inhibit GJIC in a concentration-dependent manner in H9c2 cells, in addition to causing downregulation of the gap junctional channel protein Cx43 in a concentration-dependent manner after SNPs treatment with upregulation of the level of P-Cx43.…”