Abnormally phosphorylated tau protein is the principal component of neurofibrillary tangles, accumulating in the brain in many neurodegenerative diseases, including Alzheimer’s disease. The aim of this study was to examine whether overexpression of tau protein leads to changes in the redox status of human neuroblastoma SH-SY5Y cells. The level of reactive oxygen species (ROS) was elevated in tau-overexpressing cells (TAU cells) as compared with cells transfected with the empty vector (EP cells). The level of glutathione was increased in TAU cells, apparently due to overproduction as an adaptation to oxidative stress. The TAU cells had elevated mitochondrial mass. They were more sensitive to 6-hydroxydopamine, delphinidin, 4-amino-TEMPO, and nitroxide-containing nanoparticles (NPs) compared to EP controls. These results indicate that overexpression of the tau protein imposes oxidative stress on the cells. The nitroxide 4-amino-TEMPO and nitroxide-containing nanoparticles (NPs) mitigated oxidative stress in TAU cells, decreasing the level of ROS. Nitroxide-containing nanoparticles lowered the level of lipid peroxidation in both TAU and EP cells, suggesting that nitroxides and NPs may mitigate tau-protein-induced oxidative stress.

Electrical stimulation has been used with tissue engineering-based models to develop three-dimensional (3D), dynamic, research models that are more physiologically relevant than static two-dimensional (2D) cultures. For bone tissue, the effect of electrical stimulation has focused on promoting healing and regeneration of tissue to prevent bone loss. However, electrical stimulation can also potentially affect mature bone parenchymal cells such as osteoblasts to guide bone formation and the secretion of paracrine or endocrine factors. Due to a lack of physiologically relevant models, these phenomena have not been studied in detail. In vitro electrical stimulation models can be useful for gaining an understanding of bone physiology and its effects on paracrine tissues under different physiological and pathological conditions. Here, we use a 3D, dynamic, in vitro model of bone to study the effects of electrical stimulation conditions on protein and gene expression of SaOS-2 human osteosarcoma osteoblast-like cells. We show that different stimulation regimens, including different frequencies, exposure times, and stimulation patterns, can have different effects on the expression and secretion of the osteoblastic markers alkaline phosphatase and osteocalcin. These results reveal that electrical stimulation can potentially be used to guide osteoblast gene and protein expression.