Nickel oxide nanoparticles (NiO-NPs) are an important group of nanoparticles with increasing applications in many aspects of industry. At present, there is evidence demonstrating the cytotoxic characteristics of NiO-NPs, while the involvement of autophagy in the cytotoxicity of NiO-NPs has not been reported. In this study, we aimed to study the role of autophagy in the cytotoxicity of NiO-NPs and the underlying regulatory mechanisms. First, we provided evidence that NiO-NPs induce autophagy in human cancer cells. Second, we found that the enhanced autophagic flux by NiO-NPs via the generation of intracellular reactive oxygen species (ROS) from mitochondria and the subsequent activation of the JNK pathway. Third, we demonstrated that the activation of JNK is a main force in mediating NiO-NPs-induced apoptosis. Finally, we demonstrated that the autophagic response plays an important protective role against the cytotoxic effect of NiO-NPs. Therefore, this study identifies the dual role of oxidative stress-JNK activation in the biological effects of NiO-NPs via promoting autophagy and mediating apoptosis. Understanding the protective role of autophagy and the underlying mechanism is important for the potential application of NiO-NPs in the biomedical industry.

中文翻译：

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氧化应激-JNK激活在人类癌细胞中氧化镍纳米粒子诱导的自噬和凋亡中的双重作用。

氧化镍纳米粒子（NiO-NPs）是重要的纳米粒子组，在工业的许多方面都有越来越多的应用。目前，有证据表明NiO-NP的细胞毒性特征，而自噬参与NiO-NP的细胞毒性的报道尚未报道。在这项研究中，我们旨在研究自噬在NiO-NPs的细胞毒性中的作用以及潜在的调控机制。首先，我们提供了NiO-NPs诱导人类癌细胞自噬的证据。其次，我们发现NiO-NPs通过线粒体的细胞内活性氧（ROS）的产生以及随后的JNK途径的激活增强了自噬通量。第三，我们证明了JNK的激活是介导NiO-NPs诱导的细胞凋亡的主要力量。最后，我们证明自噬反应对NiO-NPs的细胞毒性作用起重要的保护作用。因此，本研究确定了氧化应激-JNK激活通过促进自噬和介导细胞凋亡在NiO-NPs的生物学效应中的双重作用。了解自噬的保护作用及其潜在机制对于NiO-NP在生物医学行业的潜在应用至关重要。