title: Low-Dose Methylmercury-Induced Apoptosis and Mitochondrial DNA Mutation in Human Embryonic Neural Progenitor Cells.
abstract: Methylmercury (MeHg) is a long-lasting organic pollutant primarily found in the aquatic environment. The developing brain is particularly sensitive to MeHg due to reduced proliferation of neural stem cell. Although several mechanisms of MeHg-induced apoptosis have been defined in culture models, it remains unclear whether mitochondrial DNA (mtDNA) mutation is involved in the toxic effect of MeHg, especially in the neural progenitor cells. In the present study, the ReNcell CX cell, a human neural progenitor cells (hNPCs) line, was exposed to nanomolar concentrations of MeHg (≤50 nM). We found that MeHg altered mitochondrial metabolic function and induced apoptosis. In addition, we observed that MeHg induced ROS production in a dose-dependent manner in hNPCs cells, which was associated with significantly increased expressions of ND1, Cytb, and ATP6. To elucidate the mechanism underlying MeHg toxicity on mitochondrial function, we examined the ATP content and mitochondrial membrane potential in MeHg-treated hNPCs. Our study showed that MeHg exposure led to decreased ATP content and reduced mitochondrial membrane potential, which failed to match the expansion in mtDNA copy number, suggesting impaired mtDNA. Collectively, these results demonstrated that MeHg induced toxicity in hNPCs through altering mitochondrial function and inducing oxidative damage to mtDNA.
authors.affiliation: School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/WHO Collaborating Center for Occupational Health/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China.
authors.forename: Xinjin
authors.identifier: 0000-0002-7606-388X
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/WHO Collaborating Center for Occupational Health/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China.
authors.forename: Mengling
authors.initials: M
authors.lastname: Yan
authors.affiliation: School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/WHO Collaborating Center for Occupational Health/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/WHO Collaborating Center for Occupational Health/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wu
authors.affiliation: School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/WHO Collaborating Center for Occupational Health/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wu
authors.affiliation: School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/WHO Collaborating Center for Occupational Health/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China.
authors.forename: Xiuli
authors.identifier: 0000-0002-0281-1523
authors.initials: X
authors.lastname: Chang
authors.affiliation: School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/WHO Collaborating Center for Occupational Health/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China.
authors.forename: Zhijun
authors.identifier: 0000-0002-2407-2071
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D045303:Cytochromes b / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008767:Methylmercury Compounds / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D004272:DNA, Mitochondrial; C501005:MT-ATP6 protein, human; D008767:Methylmercury Compounds; D017382:Reactive Oxygen Species; D014874:Water Pollutants, Chemical; D000255:Adenosine Triphosphate; D045303:Cytochromes b; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human; D025261:Mitochondrial Proton-Translocating ATPases