Amorphous Silica Nanoparticles Inhibit Gap Junctional Intercellular Communication via Mitogen-Activated Protein Kinase Pathway

Nanoparticles;silica;gap junctional intercellular communication;Cx43;610

University:서울대학교 대학원

关键词: Nanoparticles;    silica;    gap junctional intercellular communication;    Cx43;    610;   

Others  :  http://s-space.snu.ac.kr/bitstream/10371/161546/1/000000158300.pdf

美国|英语

来源: Seoul National University Open Repository

【 摘 要 】

Amorphous silica nanoparticles (SiNPs) are widely applied in various industries. Due to their relatively safe properties in comparison with crystalline silica nanoparticles, SiNPs have been used in medical field (such as targeted drug/DNA delivery, cancer therapy, enzyme immobilization, and dentistry as an abrasive agent) as well as food industry, cosmetics, and automotive industry. However, nanoparticles should be used with caution because of their unique physical and chemical characteristics. Some studies have revealed that SiNPs possess toxicity in recent years. Data on their potential toxicities are insufficient. Thus, the objective of this study was to focus on effects of SiNPs to gap junctional intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. For characterization, SiNPs was measured by ransmission electron microscopy (TEM) and dynamic light scattering (DLS). Particle diameter of SiNPs measured by TEM was 62.79 ± 11.26 and hydrodynamic size of SiNPs measured by DLS was 69.35 nm. For GJIC experiment, the highest concentration that showed no significant cytotoxicity was determined to be 5,000µg/ml in cytotoxicity test. SiNPs inhibited dye transfer the most (by 37.75%) at 12 hours after treatment compared to negative control in time course study of scrape/loading dye transfer. Furthermore, SiNPs inhibited GJIC in a dose-dependent manner based on results of scrape/loading dye transfer, immunofluorescence staining, and western blot analysis. SiNPs phosphorylated ERK1/2 and MEK kinases, but not PKC kinases, in a dose-dependent manner. Inhibition of GJIC induced by SiNPs was significantly recovered by ERK1/2 inhibitor and MEK inhibitor, but not by PKC inhibitor. Taken together, these results suggest that SiNPs can activate a hierarchical kinase program of MAPK signaling and induce inhibition of GJIC in WB-F344 rat liver epithelial cells. SiNPs are currently applied in clinical use, so appropriate dose should be used clinically, referring to this study, in which relatively high concentrations of SiNPs inhibited GJIC.