Al₂O₃ nanoparticles induce mitochondria-mediated cell death and upregulate the expression of signaling genes in human mesenchymal stem cells

J Biochem Mol Toxicol. 2012 Nov;26(11):469-76. doi: 10.1002/jbt.21448. Epub 2012 Nov 6.

Abstract

An increase in the broad usage of Al₂O₃ nanoparticles (ANPs) in the food and agricultural sectors may produce rare hazards for human health. The objective of this study was to assess the acute toxicity of ANPs in human mesenchymal stem cells (hMSCs) in vitro. Cell viability, cellular uptake, morphology, and gene expression using quantitative real-time polymerase chain reaction (qRT-PCR) were analyzed. The results indicate that ANPs have a significant and dose-dependent effect on cytotoxicity. Control cells showed a characteristic, homogeneous nuclear staining pattern, whereas ANP-exposed cells showed abnormal nuclear morphological changes such as condensation or fragmentation. An early characteristic of apoptosis was observed in ANP-treated cells. Further confirmation of cell death in hMSCs was observed through increased expression of chosen signaling genes and also decreased expression of Bcl-2 during mitochondria-mediated cell death. Although they provide great advantages in food and agricultural products, the chronic and acute toxicity of ANPs still needs to be assessed carefully.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum Oxide / toxicity*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / agonists
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Biological Transport
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Food Technology / trends
  • Humans
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Metal Nanoparticles / toxicity*
  • Mitochondria / drug effects*
  • Oxidative Stress / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Technology, Pharmaceutical / trends
  • Toxicity Tests, Acute
  • Up-Regulation / drug effects*

Substances

  • Apoptosis Regulatory Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Aluminum Oxide