Cerium Dioxide Nanoparticles Induce Apoptosis and Autophagy in Human Peripheral Blood Monocytes

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• 作者：Salik Hussain ; Faris Al-Nsour ; Annette B. Rice ; Jamie Marshburn ; Brenda Yingling ; Zhaoxia Ji ; Jeffrey I. Zink ; Nigel J. Walker ; Stavros Garantziotis
• 刊名：ACS Nano
• 出版年：2012
• 出版时间：July 24, 2012
• 年：2012
• 卷：6
• 期：7
• 页码：5820-5829
• 全文大小：756K
• 年卷期：v.6,no.7(July 24, 2012)
• ISSN：1936-086X

文摘

Cerium dioxide nanoparticles (CeO₂ NPs) have diversified industrial uses, and novel therapeutic applications are actively being pursued. There is a 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, 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鈥?0 渭g/mL) for 20 or 40 h, 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 and overexpression of apoptosis inducing factor, but is 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 tumor 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.

Keywords:

cerium dioxide/ceria; nanoparticle; toxicity; apoptosis; autophagy; monocytes; ultrafine