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dc.contributor.authorMeili, Nicole
dc.contributor.authorChristen, Verena
dc.contributor.authorFent, Karl
dc.date.accessioned2017-01-23T05:41:11Z
dc.date.available2017-01-23T05:41:11Z
dc.date.issued2016-06-01
dc.identifier.urihttp://hdl.handle.net/11654/24027
dc.description.abstractNodularin is produced by the cyanobacterium Nodularia spumigena. It is of concern due to hepatotoxicity in humans and animals. Here we investigated unexplored molecular mechanisms by transcription analysis in human liver cells, focusing on induction of pro-inflammatory cytokines, the tumor necrosis factorα (TNF-α), endoplasmic reticulum (ER) stress and components of the activator protein-1 complex in human hepatoma cells (Huh7) exposed to non-cytotoxic (0.1 and 1 μM) and toxic concentrations (5 μM) for 24, 48, and 72 h. Transcripts of TNF-α and ER stressmarker geneswere strongly induced at 1 and 5 μMat all time-points. TNF-α led to induction of mitogen-activated protein kinases (MAPK), as demonstrated by induction of CJUN and CFOS, which form the AP-1 complex. Human primary liver cells reacted more sensitive than Huh7 cells. They showed higher cytotoxicity and induction of TNF-α and ER stress at 2.5 nM, while HepG2 cells were insensitive up to 10 μMdue to low expression of organic anion transporting polypeptides. Furthermore, nodularin led to induction of TNF-α protein, and CCAAT/enhancer-binding protein-homologous (CHOP) protein. Our data indicate that nodularin induces inflammation and ER stress and leads to activation of MAPK in liver cells. All of these activated pathways, whichwere analysed here for the first time in detail,may contribute to the hepatotoxic, and tumorigenic action of nodularin.
dc.description.urihttp://dx.doi.org/10.1016/j.taap.2016.03.014
dc.language.isoen
dc.relation.ispartofToxicology and Applied Pharmacology
dc.accessRightsAnonymous
dc.subjectNodularin
dc.subjectER stress response
dc.subjectTNF-α
dc.subjectMAPK signalling
dc.titleNodularin induces tumor necrosis factor-alpha and mitogen-activated protein kinases (MAPK) and leads to induction of endoplasmic reticulum stress
dc.type01 - Zeitschriftenartikel, Journalartikel oder Magazin
dc.volume300
dc.audienceScience
fhnw.publicationStatePublished
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publication
fhnw.InventedHereYes
fhnw.PublishedSwitzerlandNo
fhnw.pagination25-33
fhnw.IsStudentsWorkno
fhnw.publicationOnlineJa


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