skip to content
Dovepress - Open Access to Scientific and Medical Research
View our mobile site

8852

Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins

Original Research

(2316) Views  (685) Full article downloads

Authors: James CK Lai, Gayathri Ananthakrishnan, Sirisha Jandhyam, et al

Published Date September 2010 Volume 2010:5 Pages 715 - 723
DOI: http://dx.doi.org/10.2147/IJN.S5238

James CK Lai1, Gayathri Ananthakrishnan1,2, Sirisha Jandhyam1, Vikas V Dukhande1, Alok Bhushan1, Mugdha Gokhale1, Christopher K Daniels1, Solomon W Leung3
1Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy and Biomedical Research Institute, 2Department of Health and Nutrition Sciences, Kasiska College of Health Professions, 3Department of Civil and Environmental Engineering, College of Engineering and Biomedical Research Institute, Idaho State University, Pocatello, ID, USA

Abstract: 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.

Keywords: cytotoxicity, silicon dioxide nanoparticles, mitochondrial enzyme, extracellular signaling regulated kinase, cell signaling, neural cells




 

Other articles by Dr Solomon Leung



Readers of this article also read:

Evidence-based decision-making within the context of globalization: A “Why–What–How” for leaders and managers of health care organizations
Radiolucency below the crown of mandibular horizontal incompletely impacted third molars and acute inflammation in men with diabetes
The pathophysiology of bronchiectasis
Antitumor activity of silver nanoparticles in Dalton’s lymphoma ascites tumor model
Toxicologic effects of gold nanoparticles in vivo by different administration routes
Synthesis and characterization of silver/talc nanocomposites using the wet chemical reduction method
Amino acid management of Parkinson’s disease: a case study
Evaluation of in-vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi
Comparison of two treatments for coxarthrosis: local hyperthermia versus radio electric asymmetrical brain stimulation
Radio electric asymmetric brain stimulation in the treatment of behavioral and psychiatric symptoms in Alzheimer disease