Browse

ERK pathway is activated in bare-FeNPs-induced autophagy

Cited 47 time in Web of Science Cited 44 time in Scopus
Authors
Park, Eun-Jung; Umh, Ha Nee; Kim, Sang-Wook; Cho, Myung-Haing; Kim, Jae-Ho; Kim, Younghun
Issue Date
2014-02
Citation
Archives of Toxicology, Vol.88 No.2, pp.323-336
Keywords
Iron oxide nanoparticlesMacrophageAutophagyERKMitochondria
Abstract
Iron oxide nanoparticles (FeNPs) are known to be one of the most biocompatible and safe nanoparticles. However, their long-term persistence remains a problem, and macrophages play as an important mediator in continuous stimulation of the immune system due to biopersistence of nanoparticles. In the present study, we identified the mechanisms underlying the uptake and toxicity of bare-FeNPs using RAW264.7 cells, a mouse peritoneal macrophage cell line. The bare-FeNPs penetrated the cell membrane through electrostatic interactions together with the general phagocytic pathway. At 24 h after exposure, they distributed freely in the cytosol or within autophagosome-like vacuoles. Bare-FeNPs induced decrease in the cell viability along with the cell cycle arrest in G1 phase. In addition, they increased the generation of ROS and the secretion of NO and TNF alpha as well as the expression of SOD-1 and SOD-2 proteins, which are an antioxidant. While the mitochondrial calcium level, the intensity of labeled mitochondria, and ATP production decreased, the levels of autophagy-related proteins such as p62, beclin 1, ATG5, and LC3B increased in a dose-dependent manner together with the levels of ATF 3, p-EGFR, and p-ERK proteins. However, the level of p-JNK protein clearly decreased. TEM images also showed that damaged organelle exist within autophagosome-like vacuoles with bare-FeNPs. On the basis of these results, we suggest that bare-FeNPs induce autophagy by initiating oxidative stress in RAW264.7 cells. Furthermore, ERK, but not JNK, pathway is activated in bare-FeNPs-induced autophagy.
ISSN
0340-5761
URI
https://hdl.handle.net/10371/172307
DOI
https://doi.org/10.1007/s00204-013-1134-1
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse