Silica nanoparticles induce endoplasmic reticulum stress response and activate mitogen activated kinase (MAPK) signalling
dc.accessRights | Anonymous | |
dc.audience | Science | |
dc.contributor.author | Christen, Verena | |
dc.contributor.author | Fent, Karl | |
dc.date.accessioned | 2017-01-23T05:41:31Z | |
dc.date.available | 2017-01-23T05:41:31Z | |
dc.date.issued | 2016 | |
dc.description.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. | |
dc.identifier.doi | 10.1016/j.toxrep.2016.10.009 | |
dc.identifier.issn | 2214-7500 | |
dc.identifier.uri | http://hdl.handle.net/11654/24028 | |
dc.language.iso | en | en_US |
dc.publisher | Elsevier | en_US |
dc.relation.ispartof | Toxicology Reports | en_US |
dc.subject | Huh7 cells | |
dc.subject | TNF-α | |
dc.subject | MAPK | |
dc.subject | Endoplasmic reticulum stress | |
dc.subject | Silica nanoparticles | |
dc.title | Silica nanoparticles induce endoplasmic reticulum stress response and activate mitogen activated kinase (MAPK) signalling | |
dc.type | 01A - Beitrag in wissenschaftlicher Zeitschrift | |
dc.volume | 3 | |
dspace.entity.type | Publication | |
fhnw.InventedHere | Yes | |
fhnw.IsStudentsWork | no | |
fhnw.PublishedSwitzerland | No | |
fhnw.ReviewType | Anonymous ex ante peer review of a complete publication | |
fhnw.affiliation.hochschule | Hochschule für Life Sciences | de_CH |
fhnw.affiliation.institut | Institut für Ecopreneurship | de_CH |
fhnw.pagination | 832-840 | |
fhnw.publicationOnline | Ja | |
fhnw.publicationState | Published | |
relation.isAuthorOfPublication | 9bfea66d-fce8-4805-9346-f4663af0a8f1 | |
relation.isAuthorOfPublication | 7e666602-999d-4a64-8e69-cffb29e30b4b | |
relation.isAuthorOfPublication.latestForDiscovery | 7e666602-999d-4a64-8e69-cffb29e30b4b |