Silica nanoparticles induce endoplasmic reticulum stress response and activate mitogen activated kinase (MAPK) signalling. (2016)

• Record Type: Journal Article
• Authors: Christen, Verena; Fent, Karl
• Is Part Of: Toxicology reports. Volume 3(2016)
• Page Start: 832
• Page End: 840
• Publication Date: 2016
• Subjects: Silica nanoparticles -- Endoplasmic reticulum stress -- MAPK -- TNF-α -- Huh7 cells; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2016.10.009
• Languages: English
• ISSNs: 2214-7500

Abstract

Highlights: Effects of silica nanoparticles (SiO2 -NPs) were investigated in Huh7 cells. SiO2 -NPs induced ER stress response and activated MAPK pathway. SiO2 -NPs induced inflammatory reaction by induction of TNF-α. Activation of MAPK may lead to activation of AP-1 complex. Abstract: Humans may be exposed to engineered silica nanoparticles (SiO2 -NPs) but potential adverse effects are poorly understood, in particular in relation to cellular effects and modes of action. Here we studied effects of SiO2 -NPs on cellular function in human hepatoma cells (Huh7). Exposure for 24 h to 10 and 50 μg/ml SiO2 -NPs led to induction of endoplasmic reticulum (ER) stress as demonstrated by transcriptional induction of DNAJB9, GADD34, CHOP, as well as CHOP target genes BIM, CHAC-1, NOXA and PUMA . In addition, CHOP protein was induced. In addition, SiO2 -NPs induced an inflammatory response as demonstrated by induction of TNF-α and IL-8 . Activation of MAPK signalling was investigated employing a PCR array upon exposure of Huh7 cells to SiO2 -NPs. Five of 84 analysed genes, including P21, P19, CFOS, CJUN and KSR1 exhibited significant transcriptional up-regulation, and 18 genes a significant down-regulation. Strongest down-regulation occurred for the proto-oncogene BRAF, MAPK11, one of the four p38 MAPK genes, and for NFATC4 . Strong induction of CFOS, CJUN, FRA1 and CMYC was found after exposure to 50 μg/ml SiO2 -NPs for 24 h. To analyse for effects derived from up-regulation of TNF-α, Huh7 cells were exposed to SiO2 -NPs in the presence of the TNF-α inhibitor sauchinone, which reduced the induction of the TNF-α transcript by about 50%. These data demonstrate that SiO2 -NPs induce ER stress, MAPK pathway and lead to inflammatory reaction in human hepatoma cells. Health implications of SiO2 -NPs exposure should further be investigated for a risk assessment of these frequently used nanoparticles.