Cerium dioxide nanoparticles induce apoptosis and autophagy in human peripheral blood monocytes.
Cerium dioxide nanoparticles induce apoptosis and autophagy in human peripheral blood monocytes.
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DOI：
10.1021/nn302235u
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发表时间：
2012-07-24
期刊：
影响因子：
17.1
通讯作者：
Garantziotis S
中科院分区：
文献类型：
--
作者：
Hussain S;Al-Nsour F;Rice AB;Marshburn J;Yingling B;Ji Z;Zink JI;Walker NJ;Garantziotis S
二氧化铈纳米颗粒（CeO 2 NPs）具有多样化的工业用途，并且正在积极追求新的治疗应用。缺乏关于CeO 2纳米颗粒对原代人类细胞影响的机制数据。我们的目的是表征CeO 2纳米颗粒在人外周血单核细胞中的细胞毒性作用。CeO 2纳米颗粒及其悬浮液进行了彻底的表征，包括使用透射电子显微镜（TEM），动态光散射（DLS），和zeta电位分析。通过静脉切开术从健康人类志愿者抽取血液，并分离CD 14+细胞。将细胞暴露于CeO 2 NPs（0.5-10 μg/mL）20或40小时，并研究细胞损伤的机制。TEM显示CeO 2纳米颗粒被单核细胞内化，并在囊泡中或细胞质中游离。CeO 2 NP暴露导致细胞活力降低，处理的细胞表现出凋亡的特征性标志（Bax活化、线粒体膜电位丧失、DNA断裂）。CeO 2 NP毒性是由线粒体损伤引起的，导致细胞凋亡诱导因子（AIF）释放，但不是由于半胱天冬酶激活或活性氧产生。此外，CeO 2 NP暴露导致自噬，其在肿瘤抑制蛋白p53的药理学抑制后进一步增加。自噬的抑制部分逆转CeO 2纳米颗粒的细胞死亡。可以得出结论，CeO 2纳米颗粒在相对低的剂量下对原代人单核细胞具有毒性。
Cerium dioxide nanoparticles (CeO2 NPs) have diversified industrial uses and novel therapeutic applications are actively being pursued. There is lack of mechanistic data concerning the effects of CeO2 NPs on primary human cells. We aimed at characterizing the cytotoxic effects of CeO2 NPs in human peripheral blood monocytes. CeO2 NPs and their suspensions were thoroughly characterized, including using transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. Blood from healthy human volunteers was drawn through phlebotomy and CD14+ cells were isolated. Cells were exposed to CeO2 NPs (0.5–10 μg/mL) for 20 or 40 hours and mechanisms of cell injury were studied. TEM revealed that CeO2 NPs are internalized by monocytes and are found either in vesicles or free in the cytoplasm. CeO2 NP exposure leads to decrease in cell viability and treated cells exhibit characteristic hallmarks of apoptosis (activation of Bax, loss of mitochondrial membrane potential, DNA fragmentation). CeO2 NP toxicity is caused by mitochondrial damage leading to apoptosis inducing factor (AIF) release, but not due to caspase activation or reactive oxygen species production. Moreover, CeO2 NP exposure leads to autophagy, which is further increased after pharmacological inhibition of tumour suppressor protein p53. Inhibition of autophagy partially reverses cell death by CeO2 NPs. It is concluded that CeO2 NPs are toxic to primary human monocytes at relatively low doses.