ZnO nanoparticles induce apoptosis in human dermal fibroblasts via p53 and p38 pathways

Department of Biology and Center for Tissue Regeneration and Engineering, University of Dayton, Dayton, OH 45469, USA.
Toxicology in Vitro (Impact Factor: 3.21). 08/2011; 25(8):1721-6. DOI: 10.1016/j.tiv.2011.08.011
Source: PubMed

ABSTRACT The production of engineered nanoparticles is growing rapidly as the field of nanotechnology continues to expand. Zinc oxide nanoparticles (ZnO NPs) are used in various applications, including catalysis, electronics, biosensors, medicine, paints, sunscreens and cosmetics, thus it is important to understand the biological effects and risks of ZnO NPs. This study was designed to investigate the apoptosis induction by ZnO NPs via mitogen-activated protein kinase p38 and cell cycle checkpoint protein p53 pathways in human dermal fibroblasts. MTT-based cell viability assay showed a significant decrease in cell survivorship after ZnO NP exposure, and phase contrast images revealed that ZnO NP treated cells had lower density and a rounded morphology. Apoptosis induction was confirmed by the annexin V assay and Western blot analysis showed the up-regulation of p53 and phospho-p38 proteins. Furthermore, in ZnO NP exposed cells, p53 protein was phosphorylated at Ser33 and Ser46 sites known to be phosphorylated by p38. Our results suggest that ZnO NPs have the potential to induce apoptosis in human dermal fibroblasts via p53-p38 pathways.

Download full-text


Available from: Pavan Rajanahalli, Jul 28, 2015
  • Source
    • "Another study suggested that AgNPs induce cell death via up-regulation of p53-mediated apoptotic pathways [13]. AgNPs caused an increase in expression of p53, which is a tumor suppressor, p21, Noxa, Bax, and DNA damage repair proteins Rad 51 and H2AX [11] [14] [6] [15]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Silver nanoparticles (AgNPs) are gaining rapid popularity in many commonly used medical and commercial products for their unique anti-bacterial properties. The molecular mechanisms of effects of AgNPs on stem cell self-renewal and proliferation have not yet been well understood. The aim of the work is to use mouse embryonic stem cells (mESCs) as a cellular model to evaluate the toxicity of AgNPs. mESC is a very special cell type which has self-renewal and differentiation properties. The objective of this project is to determine the effects of AgNPs with different surface chemical compositions on the self-renewal and cell cycle of mESCs. Two different surface chemical compositions of AgNPs, polysaccharide-coated and hydrocarbon-coated, were used to test their toxic effects on self-renewal and proliferation of mESCs. The results indicated that both polysaccharide-coated and hydrocarbon-coated AgNPs changed the cell morphology of mESCs. Cell cycle analysis indicated that AgNPs induced mESCs cell cycle arrest at G1 and S phases through inhibition of the hyperphosphorylation of Retinoblastoma (Rb) protein. Furthermore, AgNPs exposure reduced Oct4A isoform expression which is responsible for the pluripotency of mESCs, and induced the expression of several isoforms OCT4B-265, OCT4B-190, OCT4B-164 which were suggested involved in stem cell stresses responses. In addition, the evidence of reactive oxygen species (ROS) production with two different surface chemical compositions of AgNPs supported our hypothesis that the toxic effect AgNPs exposure is due to overproduction of ROS which altered the gene expression and protein modifications. Polysaccharide coating reduced ROS production, and thus reduced the AgNPs toxicity.
    Toxicology Reports 05/2015; 411. DOI:10.1016/j.toxrep.2015.05.005
  • Source
    • "For ZnO-NP several cytotoxic effects have been reported on different cell types in 2D, whereas only a few studies have been published in 3D. It was reported that ZnO-NP decreased cell viability (Heng et al., 2010; Hsiao and Huang, 2011; Taccola et al., 2011; Zhao et al., 2012; Li et al., 2013; Sahu et al., 2013), induced oxidative stress (Fukui et al., 2012; Sahu et al., 2013), lead to DNA damage (Ng et al., 2011; Sahu et al., 2013) and induced apoptosis (Meyer et al., 2011; Ng et al., 2011). In contrast to ZnO-NP, the toxicity of TiO 2 -NP is still a point of discussion. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nanoparticles are widely employed for many applications and the number of consumer products, incorporating nanotechnology, is constantly increasing. A novel area of nanotechnology is the application in medical implants. The widespread use of nanoparticles leads to their higher prevalence in our environment. This, in turn, raises concerns regarding potential risks to humans. Previous studies have shown possible hazardous effects of some nanoparticles on mammalian cells grown in two-dimensional (2D) cultures. However, 2D in vitro cell cultures display several disadvantages such as changes in cell shape, cell function, cell responses and lack of cell-cell contacts. For this reason, the development of better models for mimicking in vivo conditions is essential.
    Journal of Biotechnology 01/2015; 205. DOI:10.1016/j.jbiotec.2015.01.001 · 2.88 Impact Factor
  • Source
    • "ZnO in nanometre scale is not attractive only for its high surface area, good biocompatibility, chemical stability and low toxicity, but it also shows unique properties, i.e. antibacterial, catalytic, optic, biomimetic and high electron communication features which make it great for potential applications in biosensoring [14] [15], biolabeling [16] or drug delivery [17] [18]. There are also literature reports about zinc oxide nanoparticles as active element in photodynamic and radiation therapies [19] [20] or in a drug delivery system of different anticancer drugs, such as daunorubicin [21] and doxorubicin [22]. The conjugates of ZnO nanoparticles with different biomolecules also offer promising means with broad range possibility of application. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The anionic zinc oxide nanoparticles have been prepared at room temperature by a precipitation method using ZnCl2 and NaOH and surface modification with 11-mercaptoundecanoic acid (MUA). Atomic force microscopy (AFM) was used for definition of morphology and size of prepared nanoparticles which was proved by measurements of particle size distribution using Zetasizer. Successful coating with MUA as surfactant was acknowledged by X-ray photoelectron spectroscopy and ATR FT-IR spectroscopy. The isoelectric point (IEP) of ZnO-MUA nanoparticles was obtained by measurements of zeta potential and FT-IR dependence on pH; the obtained value was approximately 3.58. The value of exchanged protons was 2.88 which indicates a positive binding cooperativity of modified nanoparticles.
    Applied Surface Science 10/2013; 282:342-347. DOI:10.1016/j.apsusc.2013.05.130 · 2.54 Impact Factor
Show more