Role of the mitochondrial Ca2+ uniporter in Pb2+ -induced oxidative stress in human neuroblastoma cells

Abstract Lead (Pb2+ ) has been shown to induce cellular oxidative stress, which is linked to changes in intracellular calcium (Ca2+ ) concentration. The mitochondrial Ca2+ uniporter (MCU) participates in the maintenance of Ca2+ homeostasis in neurons, but its role in Pb2+ -induced oxidative stress i...

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Published in:Brain research 2014-08, Vol.1575, p.12-21
Main Authors: Yang, Xinyi, Wang, Bin, Zeng, Hongqiang, Cai, Chunqing, Hu, Qiansheng, Cai, Shaoxi, Xu, Lei, Meng, Xiaojing, Zou, Fei
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain - drug effects
Brain - metabolism
Calcium
Calcium - metabolism
Calcium Channels - drug effects
Calcium Channels - metabolism
Cell Line, Tumor
Fundamental and applied biological sciences. Psychology
Hippocampus - drug effects
Hippocampus - metabolism
Humans
Lead (Pb2+)
Lead - toxicity
Mitochondrial Ca2+ uniporter (MCU)
Neuroblastoma
Neurology
Neurons - metabolism
Neurotoxicity
Oxidative stress
Oxidative Stress - drug effects
Rats
Rats, Wistar
Reactive Oxygen Species - metabolism
Vertebrates: nervous system and sense organs
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Summary:Abstract Lead (Pb2+ ) has been shown to induce cellular oxidative stress, which is linked to changes in intracellular calcium (Ca2+ ) concentration. The mitochondrial Ca2+ uniporter (MCU) participates in the maintenance of Ca2+ homeostasis in neurons, but its role in Pb2+ -induced oxidative stress is unclear. To address this question, oxidative stress was induced in human neuroblastoma SH-SY5Y cells and in newborn rats by Pb2+ treatment. The results showed that the production of reactive oxygen species is increased in cells upon treatment with Pb2+ 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 Pb2+ during gestation, while MCU expression was decreased. Application of the MCU activator spermine or MCU overexpression reversed Pb2+ -induced oxidative stress and inhibition of mitochondrial Ca2+ uptake, while the MCU inhibitor Ru360 and MCU knockdown potentiated the effects of Pb2+ . These results indicate that the MCU mediates the Pb2+ -induced oxidative stress response in neurons through the regulation of mitochondrial Ca2+ influx.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2014.05.032