化学
程序性细胞死亡
细胞凋亡
烟酰胺腺嘌呤二核苷酸磷酸
活性氧
NADPH氧化酶
半胱氨酸蛋白酶
蛋白酵素
组织蛋白酶
线粒体
线粒体ROS
生物化学
溶酶体
细胞生物学
生物
氧化酶试验
酶
作者
Mei Yang,Minfang Zhang,Yoshio Tahara,Svetlana A. Chechetka,Eijiro Miyako,Sumio Iijima,Masako Yudasaka
标识
DOI:10.1016/j.taap.2014.07.022
摘要
Understanding the molecular mechanisms responsible for the cytotoxic effects of carbon nanomaterials is important for their future biomedical applications. Carbon nanotubular materials induce the generation of reactive oxygen species (ROS), which causes cell death; however, the exact details of this process are still unclear. Here, we identify a mechanism of ROS generation that is involved in the apoptosis of RAW264.7 macrophages caused by excess uptake of carbon nanohorns (CNHs), a typical type of carbon nanotubule. CNH accumulated in the lysosomes, where they induced lysosomal membrane permeabilization (LMP) and the subsequent release of lysosomal proteases, such as cathepsins, which in turn caused mitochondrial dysfunction and triggered the generation of ROS in the mitochondria. The nicotinamide adenine dinucleotide phosphate oxidase was not directly involved in CNH-related ROS production, and the ROS generation cannot be regulated by mitochondrial electron transport chain. ROS fed back to amplify the mitochondrial dysfunction, leading to the subsequent activation of caspases and cell apoptosis. Carbon nanotubules commonly accumulate in the lysosomes after internalization in cells; however, lysosomal dysfunction has not attracted much attention in toxicity studies of these materials. These results suggest that LMP, a neglected mechanism, may be the primary reason for carbon nanotubule toxicity.
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