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

机译:线粒体Ca2 +单向转运蛋白在Pb2 +诱导的人神经母细胞瘤细胞氧化应激中的作用

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摘要

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.
机译:铅(Pb2 +)已显示出诱导细胞氧化应激的作用,该氧化应激与细胞内钙(Ca2 +)浓度的变化有关。线粒体Ca2 +单向转运蛋白(MCU)参与神经元中Ca2 +稳态的维持,但其在Pb2 +诱导的氧化应激中的作用尚不清楚。为了解决这个问题,通过Pb2 +处理在人神经母细胞瘤SH-SY5Y细胞和新生大鼠中诱导了氧化应激。结果表明,用Pb2 +处理后,细胞中活性氧的产生呈剂量依赖性,而谷胱甘肽和MCU表达降低。此外,在妊娠期间暴露于Pb2 +的大鼠中神经元一氧化氮合酶蛋白表达升高,而MCU表达降低。 MCU激活剂精胺或MCU过表达的应用逆转了Pb2 +诱导的氧化应激并抑制了线粒体Ca2 +的摄取,而MCU抑制剂Ru360和MCU敲低则增强了Pb2 +的作用。这些结果表明,MCU通过调节线粒体Ca2 +内流介导Pb2 +诱导的神经元氧化应激反应。

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