title: Role of the mitochondrial Ca²⁺ uniporter in Pb²⁺-induced oxidative stress in human neuroblastoma cells.
abstract: Lead (Pb(2+)) has been shown to induce cellular oxidative stress, which is linked to changes in intracellular calcium (Ca(2+)) concentration. The mitochondrial Ca(2+) uniporter (MCU) participates in the maintenance of Ca(2+) homeostasis in neurons, but its role in Pb(2+)-induced oxidative stress is unclear. To address this question, oxidative stress was induced in human neuroblastoma SH-SY5Y cells and in newborn rats by Pb(2+) treatment. The results showed that the production of reactive oxygen species is increased in cells upon treatment with Pb(2+) in a dose-dependent manner, while glutathione and MCU expression were reduced. Moreover, neuronal nitric oxide synthase protein expression was elevated in rats exposed to Pb(2+) during gestation, while MCU expression was decreased. Application of the MCU activator spermine or MCU overexpression reversed Pb(2+)-induced oxidative stress and inhibition of mitochondrial Ca(2+) uptake, while the MCU inhibitor Ru360 and MCU knockdown potentiated the effects of Pb(2+). These results indicate that the MCU mediates the Pb(2+)-induced oxidative stress response in neurons through the regulation of mitochondrial Ca(2+) influx.
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Chunqing
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Preventive Medicine, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Qiansheng
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Respiratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Shaoxi
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China. Electronic address: xiaojingmeng@smu.edu.cn.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China. Electronic address: zoufei616@163.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism*; D045744:Cell Line, Tumor; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007854:Lead / Q000633:toxicity*; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D017382:Reactive Oxygen Species; C034703:mitochondrial calcium uniporter; D007854:Lead; D002118:Calcium
keywords: Calcium; Lead (Pb(2+)); Mitochondrial Ca(2+) uniporter (MCU); Neurotoxicity; Oxidative stress