title: Methylmercury induces caspase-dependent apoptosis and autophagy in human neural stem cells.
abstract: Methylmercury (MeHg) is a well-known human neurotoxic agent whose exposure sources are mainly environmental and aquatic-derived food. MeHg is reported to induce central nervous system disability. However, the exact mechanism of MeHg-induced neurotoxicity is still unknown. In this study, to investigate which cell death signaling pathway is related with MeHg-induced cytotoxicity, the effects of MeHg on apoptosis and autophagy were evaluated in HB1.F3 human neural stem cells (NSCs). Human NSCs were treated with 1 μM of MeHg for 48 hr and the effect of MeHg on cell signaling pathway was elucidated. MeHg inhibited Akt1/mTOR signaling that led to induction of caspase-dependent apoptosis and autophagy in the NSCs. Furthermore, retinoic acid (RA)-induced neuronal differentiation was inhibited by MeHg. Taken together, these results suggest that MeHg inhibits the differentiation of human NSCs by induction of caspase-dependent apoptosis and autophagy.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Korea.
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: Hong Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Bitna
authors.initials: B
authors.lastname: Kang
authors.forename: Kyeong-Nam
authors.initials: KN
authors.lastname: Yu
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.forename: Somin
authors.initials: S
authors.lastname: Lee
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics*; D020169:Caspases / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008767:Methylmercury Compounds / Q000633:toxicity*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics*; D014212:Tretinoin / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D008767:Methylmercury Compounds; D014212:Tretinoin; D020169:Caspases; C004925:methylmercuric chloride