Journal
TOXICOLOGY IN VITRO
Volume 28, Issue 8, Pages 1402-1412Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2014.07.010
Keywords
Iron nanoparticles; Macrophages; Autophagy; Apoptosis; ER stress; ER-phagy
Categories
Funding
- Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education, Science, and Technology [2011-35B-E00011]
- National Research Foundation of Korea [21A20130000014, 35B-2011-1-E00011] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Magnetic nanoparticles have been widely used in a broad range of disciplines owing to their unique properties. However, many unexpected risks have been reported in their use. In this study, we investigated the uptake process and toxic mechanism of magnetic iron oxide nanoparticles (M-FeNPs) using RAW264.7 cells, a murine peritoneal macrophage cell line. M-FeNPs markedly enhanced the mobility of cells. At 24 h after exposure, M-FeNPs were located freely in the cytosol or within autolysosomes containing various organelles, especially the endoplasmic reticulum (ER). Cell viability decreased in a dose-dependent manner in conjunction with the arrest in S phase. ATP production also rapidly decreased together with mitochondrial damage, the number of cells that generate ROS increased, and the secretions of pro-inflammatory cytokines enhanced. The levels of oxidative stress-and ER stress-related genes were up-regulated, whereas the levels of transcription-related genes were down-regulated. Additionally, the levels of autophagy-and ER stress-related proteins increased, and the number of apoptotic cells increased with time. We also investigated the function of the autolysosome in the cellular response after exposure of M-FeNPs. When cells were exposed to M-FeNPs for 24 h with BaFA1 pretreatment, the plasma membrane disintegrated, cytosolic components disappeared, and the number of apoptotic cells significantly increased. Taken together, these results show that M-FeNPs induce autophagy preceding apoptosis through mitochondrial dysfunction and ER stress in RAW264.7 cells. Furthermore, blocking of autolysosome formation may accelerate apoptotic cell death and ER stress. (C) 2014 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available