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dc.contributor.authorChristen, Verena
dc.contributor.authorFent, Karl
dc.date.accessioned2017-01-23T05:41:31Z
dc.date.available2017-01-23T05:41:31Z
dc.date.issued2016
dc.identifier.doi10.1016/j.toxrep.2016.10.009
dc.identifier.urihttp://hdl.handle.net/11654/24028
dc.description.abstractHumans 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.description.urihttp://dx.doi.org/10.1016/j.toxrep.2016.10.009
dc.language.isoen
dc.relation.ispartofToxicology Reports
dc.accessRightsAnonymous
dc.subjectHuh7 cells
dc.subjectTNF-α
dc.subjectMAPK
dc.subjectEndoplasmic reticulum stress
dc.subjectSilica nanoparticles
dc.titleSilica nanoparticles induce endoplasmic reticulum stress response and activate mitogen activated kinase (MAPK) signalling
dc.type01 - Zeitschriftenartikel, Journalartikel oder Magazin
dc.volume3
dc.audienceScience
fhnw.publicationStatePublished
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publication
fhnw.InventedHereYes
fhnw.PublishedSwitzerlandNo
fhnw.pagination832-840
fhnw.IsStudentsWorkno
fhnw.publicationOnlineJa


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