A pivotal role of selective autophagy in mitochondrial quality control: Implications for zinc oxide nanoparticles induced neurotoxicity.

Excessive occupational, medical, and environmental exposure of zinc oxide nanoparticles (ZnONPs) caused its accumulation in the nervous system and raised global concerns over its detrimental effects. However, very few researches had been conducted on the impact of mitochondrial quality control process on central nervous system (CNS) after ZnONPs administration, including mitochondrial fission, fusion, biogenesis, and autophagy. In present study, mitochondrial dysfunction and apoptosis were triggered in ZnONPs-exposed human neuroblastoma SH-SY5Y cells. Upregulation of mitochondrial biogenesis regulator (PGC-1α) and fission proteins (Drp1) and downregulation of fusion proteins (OPA1 and Mfn2) were observed in 3 and 6 µg/mL ZnONPs-treated cells. Meanwhile, loss of mitochondrial dynamics and biogenesis was observed in the severe impaired cells (treated with 12 µg/mL ZnONPs). More, autophagy and mitophagy were significantly activated in ZnONPs-treated cells. The increased Beclin1 and LC3 II proteins, decreases of p62 protein, and activated PINK1/Parkin signaling were quantified. The autophagy agonist (Rapamycin), inhibitor (3-MA), and mitophagy inhibitor (Cyclosporine A, CsA) were employed to verify the roles of autophagy and mitophagy in ZnONPs-treated cells. Consequently, mitochondrial dysfunction and apoptosis were aggravated by the blockage of autophagy and mitophagy. Our research could be used to evaluate the risk assessment of ZnONPs exposure in CNS neurons so as to provide a crucial guideline for their future biological applications.

Selenium nanoparticles coupling with Astragalus Polysaccharides exert their cytotoxicities in MCF-7 cells by inhibiting autophagy and promoting apoptosis.

BACKGROUND: Astragalus Polysaccharides (APS) had been reported to exhibit antitumor activities. Given that nanoparticles possessed unique advantages in cancer treatment, APS was used as the modifier to prepare gold, silver and selenium nanoparticles (APS-Au, APS-Ag and APS-Se NPs) in the present study. METHODS: The three nanoparticles were synthesized via a green approach and characterized by DLS, TEM, XRD, FT-IR and UV-Vis. The inhibitory effects of these nanoparticles on various tumor cells proliferation were examined by MTT assay in vitro. Reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and the expression of apoptosis and autophagy-related proteins were also detected. RESULTS: Among these, APS-Se NPs displayed the most potent antitumor activities against MCF-7 cells in vitro. Flow cytometric analysis suggested that after cells were exposed to elevated concentrations of APS-Se NPs (10, 20 and 40 µmol/L), the rate of apoptosis was increasing (16.63 ± 0.89, 38.60 ± 3.46 and 44.38 ± 2.62%, respectively). Further analysis by immunofluorescence revealed an increase in intracellular ROS and a loss of MMP. This was accompanied by increased LC3-I to LC3-II conversion. Also, western blot analysis demonstrated that the ratios of Bax/Bcl-2 and cleaved caspase9/caspase 9 rose, and LC3-II and p62 protein levels increased. The addition of chloroquine, an inhibitor of autophagy, further enhanced protein expression of p62 and LC3-II. CONCLUSION: APS-Se NPs exerted their cytotoxic activity in MCF-7 cells by blocking autophagy and facilitating mitochondrial pathway-mediated apoptosis.