Document Detail

Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins.
MedLine Citation:
PMID:  21042417     Owner:  NLM     Status:  MEDLINE    
Recent evidence suggests silicon dioxide micro- and nanoparticles induce cytotoxic effects on lung cells. Thus, there is an increasing concern regarding their potential health hazard. Nevertheless, the putative toxicity of nanoparticles in mammalian cells has not yet been systematically investigated. We previously noted that several metallic oxide nanoparticles exert differential cytotoxic effects on human neural and nonneural cells. Therefore, we hypothesized that silicon dioxide nanoparticles induce cytotoxicity in U87 cells by lowering their survival by decreasing cell survival signaling and disturbing mitochondrial function. To investigate this hypothesis, we determined the activities of the key mitochondrial enzymes, citrate synthase and malate dehydrogenase, in astrocytoma U87 cells treated with silicon dioxide nanoparticles. In addition, we studied the expression of the mitochondrial DNA-encoded proteins, cytochrome C oxidase II and nicotinamide adenine dinucleotide (NADPH) dehydrogenase subunit 6, and cell signaling pathway protein extracellular signal-regulated kinase (ERK) and phosphorylated ERK in treated U87 cells. The activated form of ERK controls cell growth, differentiation, and proliferation. In parallel, we determined survival of U87 cells after treating them with various concentrations of silicon dioxide nanoparticles. Our results indicated that treatment with silicon dioxide nanoparticles induced decreases in U87 cell survival in a dose-related manner. The activities of citrate synthase and malate dehydrogenase in treated U87 cells were increased, possibly due to an energetic compensation in surviving cells. However, the expression of mitochondrial DNA-encoded cytochrome C oxidase subunit II and NADH dehydrogenase subunit 6 and the cell signaling protein ERK and phosphorylated ERK were altered in the treated U87 cells, suggesting that silicon dioxide nanoparticles induced disruption of mitochondrial DNA-encoded protein expression, leading to decreased mitochondrial energy production and decreased cell survival/proliferation signaling. Thus, our results strongly suggest that the cytotoxicity of silicon dioxide nanoparticles in human neural cells implicates altered mitochondrial function and cell survival/proliferation signaling.
James C K Lai; Gayathri Ananthakrishnan; Sirisha Jandhyam; Vikas V Dukhande; Alok Bhushan; Mugdha Gokhale; Christopher K Daniels; Solomon W Leung
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-10-05
Journal Detail:
Title:  International journal of nanomedicine     Volume:  5     ISSN:  1178-2013     ISO Abbreviation:  Int J Nanomedicine     Publication Date:  2010  
Date Detail:
Created Date:  2010-11-02     Completed Date:  2011-01-28     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101263847     Medline TA:  Int J Nanomedicine     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  715-23     Citation Subset:  IM    
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy and Biomedical Research Institute, Kasiska College of Health Professions.
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MeSH Terms
Astrocytoma / genetics,  metabolism*,  pathology*
Cell Line, Tumor
Cell Survival / drug effects
DNA, Mitochondrial / genetics
Intracellular Signaling Peptides and Proteins / drug effects,  metabolism
Mitochondrial Proteins / drug effects,  genetics,  metabolism
Nanoparticles / chemistry,  toxicity*
Neurons / drug effects*,  metabolism,  pathology
Silicon Dioxide / administration & dosage,  toxicity*
Grant Support
Reg. No./Substance:
0/DNA, Mitochondrial; 0/Intracellular Signaling Peptides and Proteins; 0/Mitochondrial Proteins; 7631-86-9/Silicon Dioxide
Erratum In:
Int J Nanomedicine. 2011;6:33

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