Nobiletin protects OGD/R-induced neuronal cell ferroptosis by regulating the YAP/TAZ signaling pathway
ZHANG Ling
GAO Zihong
PAN Binxian
Abstract：Objective To investigate the effect of Nobiletin(NOB)on neuronal ferroptosis induced by oxygen glucose deprivation/glucose reoxygenation(OGD/R)by regulating the Yes-associated protein(YAP)/transcriptional coactivator with PDZ-binding domain(TAZ)signaling pathway.Methods HT22 cells from mouse hippocampal neurons were cultured routinely,and a cell injury model was established by inducing OGD/R in HT22 cells.HT22 cells were induced with blank control,OGD/R,low-dose NOB(15μmol/L NOB),high-dose NOB(30μmol/L NOB)and high-dose NOB+YAP inhibitor XMU-MP-1(30μmol/L NOB+5μmol/L XMU-MP-1).CCK-8 assay was applied to detect the activity of HT22 cells in each group.Enzyme linked immunosorbent assay(ELISA)was applied to detect the levels of glutathione(GSH)and malondialdehyde(MDA)in HT22 cells of each group.Reactive oxygen species(ROS)assay kit was used to detect cellular ROS level.Specific fluorescence probe method was applied to detect intracellular iron content.Western blot was applied to detect the protein expressions of YAP/TAZ signaling pathway-related proteins and iron death marker protein solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and acyl coenzyme A synthetase long chain family member 4(ACSL4)in HT22 cells in each group.Results Compared with those of blank control,OGD/R-induced HT22 cells presented significantly lower optical density at 450nm(OD450)at 48h and 72h,GSH level and protein levels of SLC7A11 and GPX4,but higher MDA and ROS levels,iron ion level and protein levels of ACSL4,YAP and TAZ(P＜0.05).Compared with those of OGD/R-induced cells,HT22 cells induced with low-dose and high-dose NOB showed opposite changes in the above indicators(P＜0.05).Treatment of YAP inhibitor XMU-MP-1 alleviated NOB-induced inhibitory effect on OGD/R-induced ferroptosis in neurons.Conclusion NOB may alleviate OGD/R-induced neuronal ferroptosis by inhibiting the YAP/TAZ signaling pathway.
Keywords：nobiletinYes-associated protein/transcriptional coactivator with PDZ-binding domain(TAZ)signaling pathwayoxygen glucose deprivation/reoxygenationferroptosis
Publication Date：2024-11-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 3222-3226 )