PROANTHOCYANIDINS INHIBIT ERASTIN-INDUCED CELL FERROPTOSIS VIA NRF2
Objective To investigate the effect of proanthocyanidins(PC)on erastin-induced ferroptosis in human neuroblastoma SH-SY5Y cells and the mechanism of action.Methods Cell viability was detected by thiazolyl blue tetrazolium bromide(MTT)colorimetric method.Intracellular iron ion level,reactive oxygen species(ROS)level,malondialdehyde(MDA)content,glutathione(GSH)level and superoxide dismutase(SOD)activity were detected by corresponding kits.The protein expression levels of intracellular solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nfr2)and heme oxygenase 1(HO-1)were measured by Western blot assay.Results PC pretreatment was able to protect SH-SY5Y cells from erastin-induced cellular ferroptosis,mainly by inhibiting ROS production,elevated iron ion levels and MDA production,upregulating GSH levels and SOD activity.In addition,PC could also upregulate the expressions of SLC7A11 and GPX4 by activating the Nrf2/HO-1 signaling pathway,while the Nrf2 inhibitor ML385 significantly abolished the inhibitory effect of PC on intracellular ferroptosis,and the protein expressions of SLC7A11,GPX4,Nrf2 and HO-1 were decreased.Conclusion PC can inhibit erastin-induced ferroptosis,thus exerting its neuroprotective effect,and the underlying mechanism may be related to the Nrf2/HO-1 signaling pathway.[ACTA NUTRIMENTA SINICA,2024,46(1):40-47,55]
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