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

The results indicate that the MCU mediates the Pb(2+)-induced oxidative stress response in neurons through the regulation of mitochondrial Ca(2+) influx.

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.