Zinc Oxide Nanoparticles Induce Autophagy and Apoptosis via Oxidative Injury and Pro-Inflammatory Cytokines in Primary Astrocyte Cultures.
Woo-Ju SongMyung-Seon JeongDong-Min ChoiKil-Nam KimMyung-Bok WiePublished in: Nanomaterials (Basel, Switzerland) (2019)
The present study examined the potential toxic concentrations of zinc oxide nanoparticles (ZnO NPs) and associated autophagy and apoptosis-related injuries in primary neocortical astrocyte cultures. Concentrations of ZnO NPs ≥3 μg/mL induced significant toxicity in the astrocytes. At 24 h after exposure to the ZnO NPs, transmission electron microscopy revealed swelling of the endoplasmic reticulum (ER) and increased numbers of autophagolysosomes in the cultured astrocytes, and increased levels of LC3 (microtubule-associated protein 1 light chain 3)-mediated autophagy were identified by flow cytometry. Apoptosis induced by ZnO NP exposure was confirmed by the elevation of caspase-3/7 activity and 4',6'-diamidino-2-phenylindole (DAPI) staining. Significant (p < 0.05) changes in the levels of glutathione peroxidase, superoxide dismutase, tumor necrosis factor (TNF-α), and interleukin-6 were observed by enzyme-linked immunoassay (ELISA) assay following the exposure of astrocyte cultures to ZnO NPs. Phosphatidylinositol 3-kinase (PI3K)/mitogen-activated protein kinase (MAPK) dual activation was induced by ZnO NPs in a dose-dependent manner. Additionally, the Akt (protein kinase B) inhibitor BML257 and the mTOR (mammalian target of rapamycin) inhibitor rapamycin contributed to the survival of astrocytes. Inhibitors of cyclooxygenase-2 and lipoxygenase attenuated ZnO NP-induced toxicity. Calcium-modulating compounds, antioxidants, and zinc/iron chelators also decreased ZnO NP-induced toxicity. Together, these results suggest that ZnO NP-induced autophagy and apoptosis may be associated with oxidative stress and the inflammatory process in primary astrocyte cultures.
Keyphrases
- oxide nanoparticles
- oxidative stress
- diabetic rats
- room temperature
- endoplasmic reticulum stress
- quantum dots
- cell death
- signaling pathway
- reduced graphene oxide
- induced apoptosis
- high glucose
- visible light
- protein kinase
- dna damage
- cell cycle arrest
- ischemia reperfusion injury
- light emitting
- flow cytometry
- endoplasmic reticulum
- endothelial cells
- drug induced
- cell proliferation
- rheumatoid arthritis
- gold nanoparticles
- nitric oxide
- tyrosine kinase
- heat shock
- anti inflammatory
- heat stress
- free survival