Study on the mechanism of mitochondrial oxidative damage and dysfunction of nerve cells by Silica nanoparticles
摘要：OBJECTIVE Silica nanoparticles（Si NPS） have been widely used in industry, electronics and pharmaceutical industries. It is widely used in medicine, tumor treatment and diagnosis, and other biomedical and biotechnology fields. The opportunities for people to the exposure to SiNPS through iatrogenic, occupational and environmental exposureare gradually increasing. The damage and biological effects of SiNPS on the nervous system have attracted widespread attention in the field of toxicology. Central nerve cells are rich in mitochondria. The maintenance of membrane potential of nerve cells, the synthesis and operation of neurotransmitters, and the transmission of nerve impulses,etc., require energy and information support, which will all be provided by mitochondria. When cells are exposed to foreign compounds, the balance between oxidation and anti-oxidation in the cells is broken, and the function of mitochondria changes accordingly. However, the specific mechanism of SiNPS damage to nerve cell mitochondria is still unclear. In this study, SH-SY5 Y cells were used as the target cells to investigate the effect and mechanism of Si NPSon the oxidative damage and dysfunction of nerve cell mitochondria. METHODS The MTT method was used to detect the influence of SiNPS on the survival rate of SH-SY5 Y cells; the biochemical method was used to detect the SOD and GSH-Px activities in the cells and mitochondria; the intracellular ROS content was observed by fluorescence microscope; the flow cytometry was used to detect apoptosis and mitochondria changes of membrane potential; Western blot method was used to detect the expression of Mn-SOD, VDAC1, COXI,UCP2, PRDX3 relatedto mitochondrial damage induced by SiNPS in cells and mitochondria. RESULTS Different doses of SiNPS exposed to cells for 24 hours can reduce cell survival; after the cellswere treated with SiNPS for 3 hours, the mitochondrial membrane potential decreased and reactive oxygen species increased; intracellular SOD activity decreased, mitochondrial Mn-SOD activity increased, intracellular and mitochondrial GSH-Px activity increased; SOD protein expression levels in cells decreased,VDAC1, COXI, UCP2, PRDX3 related protein expression levels increased, Mn-SOD, VDAC1, COXI, UCP2,PRDX3 related protein expression levels in mitochondria increased with the increase of SiNPS concentration. CONCLUSIONS SiNPS has a toxic effect on SH-SY5 Y cells, and leads to oxidative damage to cells, as well as oxidative damage to cell mitochondria and changes in the expression of mitochondrial function-related proteins, which may eventually induce SH-SY5 Y nerve cell apoptosis.