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Brain Res. 2014 Aug 5;1575:12-21. doi: 10.1016/j.brainres.2014.05.032. Epub 2014 Jun 2.

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

Author information

  • 1Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
  • 2Department of Preventive Medicine, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China.
  • 3Department of Respiratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 4Department 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.
  • 5Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China. Electronic address: zoufei616@163.com.

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.

Copyright © 2014 Elsevier B.V. All rights reserved.

KEYWORDS:

Calcium; Lead (Pb(2+)); Mitochondrial Ca(2+) uniporter (MCU); Neurotoxicity; Oxidative stress

PMID:
24881885
[PubMed - indexed for MEDLINE]
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