Nrf2 participates in neurocytotoxicity caused by CaMKⅡ inhibition
Objective To investigate the effect of Ca2+/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)specific inhibitor KN93 on nerve cells and its relationship with Nrf2 pathway.Methods Mouse brain neuroma cell N2a was cultured,and the correlation between the toxicity of KN93 on cells and the concentration after 12 h was determined by CCK8 detection;5 μmol KN93 was applied for 12 h after administration,and the survival rate of cells was detected by fluorescent NeuN staining;the effect of KN93 on the expression of inflammatory factors TNF-α and IL-1β was detected by ELISA kit;the change of Nrf2 protein expression after administration of KN93 was detected by Western blot;the change of inflammation-related factors TNF-α and IL-1β expression was detected by ELISA kit when KN93 and Nrf2 antagonist ML385 were treated at the same time.Results Compared with the control group,5 μmol KN93 was applied for 12 h,and the positive cells of NeuN staining in the KN93 group were significantly reduced;the expression of TNF-α and IL-1β was significantly increased;the expression of Nrf2 protein was significantly increased;compared with the KN93 group,the expression of inflammation-related proteins in the KN93 and Nrf2 antagonist ML385 simultaneous treatment group was decreased,that is,the inhibitor of Nrf2 ML385 could reverse the inflammatory response induced by KN93.Conclusion Nrf2 is involved in theneurocytotoxicity caused by CaMKⅡ inhibitor KN93 by inducing inflammatory response.
Ca2+/calmodulin-dependent protein kinase ⅡKN93epilepsyN2aNrf2
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