The role of HSP90a in methamphetamine/hyperthermia-induced necroptosis in rat striatum neurons

摘要

Methamphetamine(METH)is one of the most widely abused synthetic drugs in the world,with the abuser present hyperthermia(HT)and psychiatric symptoms.However,the mechanism involved in METH/HT-induced neurotoxicity remains elusive.Here,we investigated the role of heat shock protein 90 alpha(HSP90a)in METH/HT(39.5C)-induced necroptosis in rat striatum neurons and rat in vivo model.Western blot showed that the expression of HSP90a increased,and HSP90a specific inhibitor geldanamycin(GA)and shRNA of HSP90a could attenuate METH/HT-induced upregulation of receptor interacting protein 3(RIP3),pRIP3,mixed lineage kinase domain-like protein(MLKL)and pMLKL in cultured striatum neurons and in vivo model.Propidium iodide staining and lactate dehydrogenase assay results showed that METH/HT-induced necroptosis is partially inhibited by both necrostain-1,GA and shRNA of HSP90a in vitro and in vivo model.