期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 153, 期 -, 页码 173-186出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2020.03.027
关键词
Apoptosis; Autophagy; NiO-NPs; Oxidative stress; JNK; ROS
资金
- NUS Research Scholarship
- NUS NGS scholarship
- Singapore National Medical Research Council [NMRC/CIRG/1490/2018]
- Ministry of Education grant [MOE2018-T2-1-060]
- Twasol Research Excellence Program (TRE Program), King Saud University, Saudi Arabia
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.
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