title: 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.
authors.affiliation: Department of Occupational and Environmental Health Science, Peking University School of Public Health, Beijing, China.
authors.forename: Furong
authors.initials: F
authors.lastname: Deng
authors.forename: Ping
authors.initials: P
authors.lastname: Olesen
authors.forename: Rasmus
authors.initials: R
authors.lastname: Foldbjerg
authors.forename: Duy Anh
authors.initials: DA
authors.lastname: Dang
authors.forename: Xinbiao
authors.initials: X
authors.lastname: Guo
authors.forename: Herman
authors.initials: H
authors.lastname: Autrup
mesh_terms: D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018031:Connexin 43 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D011145:Polyvinyls / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012834:Silver / Q000494:pharmacology*; D012835:Silver Nitrate / Q000494:pharmacology; D013499:Surface Properties; D015854:Up-Regulation
chemical_list: D018031:Connexin 43; D011145:Polyvinyls; D011759:Pyrrolidines; C505150:poly(N-vinylpyrrolidine); D012834:Silver; D012835:Silver Nitrate