Loss of gap junctional intercellular communication in rat lung epithelial cells exposed to carbon or silica-based nanoparticles.
The aim of this study was to investigate whether fine and ultrafine carbon black (fC and ufC), and fine and ultrafine silica (fS, ufS) particles affect gap junctional intercellular communication (GJIC) in rat lung epithelial cells. Exposure of cells to subcytotoxic doses of ufC, fS and ufS resulted in a 63%, 59% and 77% reduction of GJIC, respectively, as determined in a dye transfer assay. In contrast to ufC, fC did not significantly alter GJIC. Changes in subcellular localization of the major gap junction protein in RLE cells, connexin-43 (Cx43), and of β-catenin were observed in cells exposed to ufC, fS or ufS. The loss of GJIC was counteracted by N-acetyl cysteine and was largely prevented by specific inhibitors of epidermal growth factor receptor-dependent signaling, pointing to the crucial role of two known major mediators of nanoparticle action, namely reactive oxygen species and membrane-receptor signaling, in particle-induced modulation of GJIC.
Ale-Agha
Niloofar
N
Leibniz-Institut für umweltmedizinische Forschung (IUF), Auf'm Hennekamp 50, Düsseldorf, Germany.
Albrecht
Catrin
C
Klotz
Lars-Oliver
LO
D000818:Animals; D002244:Carbon / Q000633:toxicity; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D066246:ErbB Receptors / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D007546:Isoquinolines; D008168:Lung / Q000166:cytology / Q000378:metabolism; D053758:Nanoparticles / Q000633:toxicity; D010766:Phosphorylation; D051381:Rats; D012822:Silicon Dioxide / Q000633:toxicity; D051176:beta Catenin / Q000378:metabolism
D018031:Connexin 43; D017630:Connexins; D007546:Isoquinolines; D051176:beta Catenin; D002244:Carbon; D012822:Silicon Dioxide; C017475:lucifer yellow; C483803:Egfr protein, rat; D066246:ErbB Receptors