4.5 Article

Effects of DMSA-Coated Fe3O4 Nanoparticles on the Transcription of Genes Related to Iron and Osmosis Homeostasis

Journal

TOXICOLOGICAL SCIENCES
Volume 131, Issue 2, Pages 521-536

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfs300

Keywords

DMSA-coated Fe3O4 nanoparticles; gene transcription; iron and osmosis homeostasis

Categories

Funding

  1. National Important Science Research Program of China [2011CB933503, 2006CB933205]
  2. Technology Support Program of Jiangsu [BE2012741]
  3. Scientific Research Foundation of Graduate School of Southeast University [YBJJ1126]

Ask authors/readers for more resources

In this article, we checked the effect of 2,3-dimercaptosuccinic acid-coated Fe3O4 nanoparticles on gene expression of mouse macrophage RAW264.7 cells and found that the transcription of several important genes related to intracellular iron homeostasis were significantly changed. We thus speculated that the cellular iron homeostasis might be disturbed by this nanoparticle through releasing iron ion in cells. To verify this speculation, we first confirmed the transcriptional changes of several key iron homeostasis- related genes, such as Tfrc, Trf, and Lcn2, using quantitative PCR, and found that an iron ion chelator, desferrioxamine, could alleviate the transcriptional alterations of two typical genes, Tfrc and Lcn2. Then, we designed and validated a method based on centrifugation for assaying intracellular irons in ion and nanoparticle state. After extensive measures of intracellular iron in two forms and total iron, we found that the intracellular iron ion significantly increased with intracellular total iron and nanoparticle iron, demonstrating degradation of this nanoparticle into iron ion in cells. We next mimicked the intralysosomal environment in vitro and verified that the internalized iron nanoparticle could release iron ion in lysosome. We found that as another important compensatory response to intracellular overload of iron ion, cells significantly downregulated the expressions of genes belonging to solute carrier family which are responsible for transferring many organic solutes into cells, such as Slc5a3 and Slc44a1, in order to prevent more organic solutes into cells and thus lower the intracellular osmosis. Based on these findings, we profiled a map of gene effects after cells were treated with this iron nanoparticle and concluded that the iron nanoparticles might be more detrimental to cell than iron ion due to its intracellular internalization fashion, nonspecific endocytosis.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available