Inhibitory Effect of Nurr1 on Apoptosis,Autophagy and Ferroptosis of LPS-induced Microglia
Objective To investigate the effect of nuclear receptor-related protein 1(Nurr1)on the viability including apoptosis,autophagy and ferroptosis of BV2 microglial cells induced by bacterial lipopolysaccharide(LPS),so as to explore the neuroprotective effect of Nurr1.Methods BV2 cells were cultured and divided into Ctrl group,LPS group,C-DIM12 group(Nurr1 specific agonist),LPS+C-DIM12 group.Western blot was used to observe the expression of TLR4 and Caspase3,and flow cytometry was used to detect apoptosis.The expression changes of autophagy protein LC3 Ⅱ and ferroptosis marker glutathione peroxidase4(GPX4)and MDA were detected after activating the expression activity of Nurr1 with the specific agonist C-DIM 12 of Nurr1.Results After LPS activated BV2 cells,the expression of TLR4 and Caspase3 increased significantly(P>0.05).After activating Nurr1 by C-DIM12,the expression of TLR4 and Caspase3 decreased significantly(P>0.05).Flow cytometry also showed that the activation of Nurr1 inhibited cell apoptosis.After C-DIM12 activated Nurr1,the expression of autophagic protein LC3 Ⅱ was obviously decreased compared with LPS group,and the expression of ferroptosis protein GPX4 was remarkably increased,but MDA level decreased.Conclusion Nurr1 may play a neuroprotective role by inhibiting LPS-induced apoptosis,autophagy and ferroptosis of microglia.Nurr1 may be a potential target for the treatment of central nervous system diseases.