Article

Cerium dioxide nanoparticles induce apoptosis and autophagy in human peripheral blood monocytes.

Clinical Research Unit, National Institute of Environmental Health Sciences/National Institute of Health, Research Triangle Park 27709, North Carolina, United States.
ACS Nano (impact factor: 10.77). 06/2012; 6(7):5820-9. DOI:10.1021/nn302235u pp.5820-9
Source: PubMed

ABSTRACT Cerium dioxide nanoparticles (CeO(2) NPs) have diversified industrial uses, and novel therapeutic applications are actively being pursued. There is a lack of mechanistic data concerning the effects of CeO(2) NPs on primary human cells. We aimed at characterizing the cytotoxic effects of CeO(2) NPs in human peripheral blood monocytes. CeO(2) 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 CeO(2) NPs (0.5-10 μg/mL) for 20 or 40 h, and mechanisms of cell injury were studied. TEM revealed that CeO(2) NPs are internalized by monocytes and are found either in vesicles or free in the cytoplasm. CeO(2) 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). CeO(2) 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, CeO(2) 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 CeO(2) NPs. It is concluded that CeO(2) NPs are toxic to primary human monocytes at relatively low doses.

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Keywords

Bax
 
caspase activation
 
cell injury
 
cell viability
 
cells exhibit characteristic hallmarks
 
DNA fragmentation
 
dynamic light scattering
 
healthy human volunteers
 
Inhibition
 
mechanistic data
 
mitochondrial damage
 
mitochondrial membrane potential
 
pharmacological inhibition
 
primary human cells
 
primary human monocytes
 
reactive oxygen species production
 
TEM
 
transmission electron microscopy
 
tumor suppressor protein p53
 
zeta potential analysis