title: Methylmercury inhibits differentiation of rat neural stem cells via Notch signalling.
abstract: The Notch receptor is essential for neural stem cell (NSC) characteristics. Relatively high concentrations (micromolar) of methylmercury (MeHg) activate Notch signalling in Drosophila cell lines; however, exposure of MeHg at such concentrations is rare, and the implications for mammalian cells are unclear. We have shown that MeHg at a nanomolar range inhibits neuronal differentiation of rodent embryonic NSCs. Here we show that low MeHg levels (2.5-10 nM) activated Notch signalling in NSCs, as assessed by the increased activity in a specific Notch-reporter assay and by the increased cleavage of the Notch intracellular domain. Importantly, pretreatment with Notch cleavage inhibitor reversed the MeHg-induced repression of neuronal differentiation, suggesting that Notch activation is involved in the inhibition of NSC differentiation by environmentally relevant levels of MeHg.
authors.affiliation: Division of Toxicology and Neurotoxicology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Tamm
authors.forename: Joshua K
authors.initials: JK
authors.lastname: Duckworth
authors.forename: Ola
authors.initials: O
authors.lastname: Hermanson
authors.forename: Sandra
authors.initials: S
authors.lastname: Ceccatelli
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology; D005260:Female; D008345:Manganese / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D008767:Methylmercury Compounds / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects*; D013687:Telencephalon / Q000166:cytology; D014162:Transfection
chemical_list: D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; D008767:Methylmercury Compounds; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D051880:Receptors, Notch; D008345:Manganese