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Published on: February 3, 2017
ERK pathway is activated in bare-FeNPs-induced autophagy
Eun-Jung Park1, Ha Nee Umh, Sang-Wook Kim
1Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea, world1@ajou.ac.kr.
Archives of Toxicology
|September 27, 2013
Summary
Iron oxide nanoparticles (FeNPs) persist in macrophages, triggering immune responses. This study reveals FeNPs induce autophagy via oxidative stress, activating the ERK pathway in RAW264.7 cells.
Area of Science:
- Nanotechnology
- Cell Biology
- Immunotoxicology
Background:
- Iron oxide nanoparticles (FeNPs) exhibit biocompatibility but face challenges with long-term persistence.
- Persistent nanoparticles can continuously stimulate the immune system, particularly via macrophages.
- Understanding FeNP interactions with macrophages is crucial for assessing their safety and biological impact.
Purpose of the Study:
- To elucidate the mechanisms of bare-FeNP uptake and toxicity in RAW264.7 macrophage cells.
- To investigate the cellular responses, including oxidative stress and autophagy induction, following FeNP exposure.
- To identify the signaling pathways involved in FeNP-induced cellular effects.
Main Methods:
- Utilized RAW264.7 mouse peritoneal macrophage cell line for experiments.
- Investigated FeNP uptake via electrostatic interactions and phagocytosis.
- Assessed cell viability, cell cycle, reactive oxygen species (ROS), nitric oxide (NO), TNF-alpha, antioxidant protein expression (SOD-1, SOD-2), mitochondrial function, and autophagy markers.
- Employed Transmission Electron Microscopy (TEM) to visualize cellular damage.
Main Results:
- Bare-FeNPs were internalized through electrostatic interactions and phagocytosis, distributing within the cytosol and autophagosomes.
- FeNP exposure led to decreased cell viability, G1 phase cell cycle arrest, and increased ROS, NO, and TNF-alpha secretion.
- Mitochondrial function (calcium, ATP) decreased, while autophagy markers (p62, beclin 1, ATG5, LC3B) and oxidative stress indicators (ATF3, p-EGFR, p-ERK) increased.
- TEM revealed damaged organelles within FeNP-containing autophagosomes.
Conclusions:
- Bare-FeNPs induce autophagy in RAW264.7 cells, primarily by initiating oxidative stress.
- The extracellular signal-regulated kinase (ERK) pathway is activated, whereas the c-Jun N-terminal kinase (JNK) pathway is suppressed during FeNP-induced autophagy.
- These findings highlight the complex interplay between FeNP persistence, oxidative stress, and cellular defense mechanisms like autophagy.
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