The Inhibition of ERK Activation Mediates the Protection of Necrostatin-1 on Glutamate Toxicity in HT-22 Cells

摘要: Receptor-interacting protein 1 (RIP1), a molecular switch from apoptosis to necroptosis, is regarded play an essential role in necroptotic cell death. Although the increased RIP1 activity induced by tumor necrosis factor α activates mitogen-activated kinases (MAPKs) including ERK and leads apoptotic or necrotic death, it unclear what of during process necroptosis. In this study, our data demonstrated that inhibitors U0126 PD98059 blocked glutamate-induced necroptosis HT-22 cells, indicating critical activation Further, we found glutamate treatment phosphorylated ERK1/2 level, but specific inhibitor Necrostatin-1 (Nec-1) significantly inhibited phosphorylation ERK1 (P44) at 5, 10, 15 min after treatment; ERK2 (P42) level was also markedly reduced Nec-1 10 treatment. The JNK P38, two other MAPK members, were slightly treatment, had no inhibitory effect on P38 activation. Our finding suggested may important death inhibition mediated protection Since considered as downstream RIP1, RIP1/ERK signal pathway provide new therapeutic avenues for ischemia–reperfusion damage neurodegenerative diseases-containing