P38 MAPK Mediated Pyroptosis Of NaAsO₂ Exposed Mouse Hippocampal Neurons

Objective:To investigate whether NaAsO₂ can activate NLRP3 inflammasomes by regulating the MAPK signaling pathway and thus cause pyroptosis.Methods:The HT-22 cell was purchased from Beijing Beina Chuanglian Biotechnology Research Institute,Chinese Academy of Sciences.The CCK-8 method was used to detect the effects of different concentrations of NaAsO₂（0-35μM）on the proliferation and viability of HT-22 cells.Western blot method was used to detect the expression levels of MAPK signal pathway protein、the protein Related to pyroptosis NLRP3,ASC,caspase-1 p20,GSDMD-N and IL-1β、IL-18.LDH release kit was used to detect LDH release.Results:1.NaAsO₂ induces pyroptosis in HT-22:Compared with the 0 group,thetreatment of NaAsO₂（4,6,8μM）significantly increased the protein levels of NLRP3,ASC,caspase-1 p20,GSDMD-N,IL-1β,and IL-18（P<0.01）.Compared with the 0group,the treatment of NaAsO₂（6,8μM）significantly increased the level of LDHrelease（P<0.01）.2.Role of MAPK signaling pathway in the pyroptosis of HT-22 cells induced by NaAs O₂:Compared with the 0 group,the treatment of NaAsO₂（4,6,8μM）significantly increased p-p38 protein levels（P<0.01）.Compared with SB202190（-）group,the treatment ofNaAsO₂（8μM）significantly increased the protein levels of NLRP3,ASC,caspase-1 p20,GSDMD-N,IL-1β,and IL-18（P<0.01）.Compared with NaAsO₂ group,SB202190pretreatment significantly inhibited the expressions of NLRP3,ASC,caspase-1 p20,GSDMD-N,IL-1β,and IL-18 protein level,and the differences were statistically significant（P<0.01）.Compared with the NaAsO₂ group,the pretreatment of SB202190significantly inhibited LDH release levels.The differences were statistically significant（P<0.01）.Conclusion:NaAsO₂ induces pyroptosis of mouse hippocampal neuron cell HT-22 by activating p38 MAPK.