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Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling.

Authors
Apopa-PL; Qian-Y; Shao-R; Guo-NL; Schwegler-Berry-D; Pacurari-M; Porter-D; Shi-X; Vallyathan-V; Castranova-V; Flynn-DC
Source
Part Fibre Toxicol 2009 Jan; 6:1
NIOSHTIC No.
20035036
Abstract
Background: engineered iron nanoparticles are being explored for the development of biomedical applications and many other industry purposes. However, to date little is known concerning the precise mechanisms of translocation of iron nanoparticles into targeted tissues and organs from blood circulation, as well as the underlying implications of potential harmful health effects in human. Results: the confocal microscopy imaging analysis demonstrates that exposure to engineered iron nanoparticles induces an increase in cell permeability in human microvascular endothelial cells. Our studies further reveal iron nanoparticles enhance the permeability through the production of reactive oxygen species (ROS) and the stabilization of microtubules. We also showed Akt/GSK-3 signaling pathways are involved in iron nanoparticle-induced cell permeability. The inhibition of ROS demonstrate ROS play a major role in regulating Akt/GSK-3 -- mediated cell permeability upon iron nanoparticle exposure. These results provide new insights into the bioreactivity of engineered iron nanoparticles which can inform potential applications in medical imaging or drug delivery. Conclusion: our results indicate that exposure to iron nanoparticles induces an increase in endothelial cell permeability through ROS oxidative stress-modulated microtubule remodeling. The findings from this study provide new understandings on the effects of nanoparticles on vascular transport of macromolecules and drugs.
Keywords
Biological-factors; Biological-monitoring; Biological-transport; Biological-effects; Biological-function; Biochemical-analysis; Biochemical-indicators; Biochemistry; Biomedical-engineering; Blood-vessels; Blood-cells; Cell-biology; Cell-metabolism; Cell-wall-permeability; Cellular-function; Cellular-reactions; Cellular-transport-mechanism; Drug-receptor; Drug-therapy; Exposure-levels; Exposure-methods; Genes; Laboratory-animals; Laboratory-testing; Medical-monitoring; Medical-research; Medical-treatment; Medicinal-chemicals; Particulates; Particulate-dust; Tissue-distribution; Nanotechnology
Contact
Yong Qian, The Pathology and Physiology Research Branch, Health Effects Laboratory Division, CDC, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
CAS No.
7439-89-6
Publication Date
20090109
Document Type
Journal Article
Email Address
yaq2@cdc.gov
Fiscal Year
2009
NTIS Accession No.
NTIS Price
ISSN
1743-8977
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Particle and Fibre Toxicology
State
WV
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