Nodularin induces tumor necrosis factor-alpha and mitogen-activated protein kinases (MAPK) and leads to induction of endoplasmic reticulum stress
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Autor:innen
Autor:in (Körperschaft)
Publikationsdatum
01.06.2016
Typ der Arbeit
Studiengang
Sammlung
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Toxicology and Applied Pharmacology
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
300
Ausgabe / Nummer
Seiten / Dauer
25-33
Patentnummer
Verlag / Herausgebende Institution
Elsevier
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
Nodularin 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.
Schlagwörter
Nodularin, ER stress response, TNF-α, MAPK signalling
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
1096-0333
0041-008X
0041-008X
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Zukunftsfelder FHNW
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
MEILI, Nicole, Verena CHRISTEN und Karl FENT, 2016. Nodularin induces tumor necrosis factor-alpha and mitogen-activated protein kinases (MAPK) and leads to induction of endoplasmic reticulum stress. Toxicology and Applied Pharmacology. 1 Juni 2016. Bd. 300, S. 25–33. DOI 10.1016/j.taap.2016.03.014. Verfügbar unter: http://hdl.handle.net/11654/24027