Midazolam prevents motor neuronal death from oxidative stress attack mediated by JNK-ERK pathway

Abstract

Midazolam is a sedative used by patients with mechanical ventilation. However, the potential clinical value is not fully explored. In this report, we made use of a neuroblastoma-spinal cord hybrid motor neuron-like cell line NSC34, and elucidated the potential role of Midazolam on these cells under the insult of oxidative stress. We found the protective effect of Midazolam on motor neurons against cytotoxicity induced by the combination of oligomycin A and rotenone (O/R) or phenylarsine oxide. The characteristics of apoptosis, such as the ratio of TUNEL+ cells or the expression level of cleaved Caspase-3, was decreased by 22 or 45% in the presence of Midazolam. Furthermore, this effect was correlated with the JNK-ERK signaling pathway. Either phosphorylation of ERK or JNK was positively or negatively modulated with the treatment of Midazolam in NSC34 cells attacked by reactive oxygen species. Meanwhile, inhibition or activation of the JNK-ERK pathway regulated the protective effect of Midazolam on NSC34 cells with oxidative stress insult. Collectively, this study elucidated a previously unidentified clinical effect of Midazolam, and put forward the great promise that Midazolam may be considered as a potential candidate to the treatment of motor neuron disease.

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