title: Low dose of methylmercury (MeHg) exposure induces caspase mediated-apoptosis in cultured neural progenitor cells.
abstract: Methylmercury (MeHg) is an environmental pollutant known to cause neurobehavioral defects, and it is especially toxic to the developing brain. In contrast to the adult, the developing brain consists of a large number of dividing neural progenitor cells (NPCs), which are vulnerable targets for MeHg toxicity. In a previous study, we showed that the embryonic NPCs from the telencephalon are more sensitive to MeHg than other neural cells. Here, we investigated the mechanism of cell death underlying MeHg toxicity. We observed that exposure of NPCs to MeHg caused DNA laddering in a dose- and time-dependent manner. Decreased pro-caspase3 and increased cleaved-caspase3 protein was observed 3-12 hours after incubation of NPCs with MeHg. Moreover, the caspase-inhibitor Z-VAD FMK significantly suppressed MeHg-induced cell death in a dose-dependent manner. These results suggest that environmentally relevant levels of MeHg exposure induce apoptosis in NPCs.
authors.affiliation: Department of Anatomy, Showa University School of Medicine.
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakamachi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ohtaki
authors.forename: Akira
authors.initials: A
authors.lastname: Naganuma
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakajo
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism / Q000502:physiology*; D061945:Caspase Inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D058953:Neural Stem Cells / Q000187:drug effects* / Q000502:physiology*; D013687:Telencephalon / Q000166:cytology; D013997:Time Factors
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D004785:Environmental Pollutants; D008767:Methylmercury Compounds; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D004247:DNA; D053148:Caspase 3