Dexmedetomidine is Resistant to Ferroptosis by Activating mTOR-TFR1 Signaling

Abstract

Background: With the development of society, Neurodegenerative disease (ND), such as alzheimer's disease, is more and more important to the researchers. Metal iron may play a crucial role in this disease, so our research constructed the iron overloading model in nerve cells, induce the ferroptosis, simulate the state of the nerve in the body, and used the anesthesia Dexmedetomidine (Dex), and study whether the Dex can inhibit the ferroptosis and reduce the ND.Methods: Cell proliferation kit CCK8 and PI/Hoechst fluorescence double staining were used to detect the proliferation and apoptosis of HT22 cells. Western blot (WB) was used to detect the expression of PTGS2 and ACSL4, pathway proteins mTOR, TFR1. ROS content in HT22 cells was determined by DHE fluorescence probe. Lipid Peroxidation in nerve cells was detected by MDA Assay. Mito-ferrorange fluorescent probe was used to detect the level of ferrous ions in cells to demonstrate that ferroptosis occurred in nerve cells and Dex could protect nerve cells from ferroptosis.Results: Dex inhibits ferroptosis by regulating the mTOR-TFR1 pathway, reducing lipid peroxidation, intracellular reactive oxygen accumulation (ROS), reducing iron ions, and alleviating mitochondrial damage. mTOR is a well-known autophagy target and has been found to be closely related to ferroptosis. Dex activates the mTOR pathway, inhibits iron entry into the cell, reduces iron influx, and prevents ferroptosis by fenton reaction between excessive iron and lipids in the cell.Conclusion: Dex protects nerve cells from ferroptosis by regulating the mTOR-TFR1 pathway.

Synergistic effect of spermidine and ciprofloxacin against Alzheimer disease in male rat via ferroptosis modulation

“…The expression of TfR1, involved in iron uptake, was signi cantly elevated in the AD model group. Cotreatment with spermidine and/or cipro oxacin modulated TfR1 expression, possibly through mTOR signaling regulation to inhibit TfR1 overexpression, leading to ferroptosis modulation (Ding et al, 2021). Furthermore, Immunohistochemical analysis showed positive staining for p53 in the hippocampus of the AD model group, which may be related to neuronal cell death and accumulation of p53 oligomers (Farmer et al, 2020).…”