[Glutathione-rich yeast extract inhibits EtOH-induced ferroptosis of HepG2 cells by activation of nuclear factorer-related actor 2].

OBJECTIVE

To investigate the ameliorative effect of glutathione-rich yeast extract(GYE) on ferroptosis of HepG2 cells induced by ethanol(EtOH) and to further explore the potential molecular mechanism based on regulating nuclear factorer-related actor 2(Nrf2).

METHODS

HepG2 cells were induced with 100 mmol/L EtOH and intervened by 0.1 and 0.5 mmol/L GYE. The levels of Fe~(2+), lipid peroxides in the cells was detected by fluorescent probe. The occurrence of ferroptosis was assessed by Hoechst/PI staining. The protein expression of glutathione peroxidase 4(GPX4), recombinant solute carrier family 7, member 11(SLC7A11), prostaglandin-endoperoxidesynthase 2(ptgs2)and acyl-CoA synthetase long-chain family 4(ACSL4)were detected by Western blot. Nuclear translocation of Nrf2 and GPX4 expression and were detected by immunofluorescence staining.

RESULTS

Compared with the Control group, the EtOH group showed a significant increase in Fe~(2+)(P<0.05), intracellular lipid peroxides and ferroptosis in HepG2 cells(P<0.05). In addition, EtOH treatment decreased the protein expression of GPX4 and SLC7A11 and increased the protein expression of ACSL4 and ptgs2(P<0.05). GYE treatment significantly mitigated EtOH-induced Fe~(2+) accumulation and overproduction of lipid peroxides(P<0.05). Also, GYE treatment significantly inhibited EtOH-induced ferroptosis of HepG2 cells(P<0.05), and the inhibition effect was better in the high-dose GYE group. GYE treatment significantly promoted nuclear translocation of Nrf2(P<0.05).

CONCLUSION

GYE can effectively inhibit EtOH-induced ferroptosis in HepG2 cells, and its molecular mechanism may be related to the up-regulating Nrf2.