Cu-Zn SOD suppresses epilepsy in pilocarpine-treated rats and alters SCN2A/Nrf2/HO-1 expression
Fang Wen
Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, 410011 Hunan Province, China
Search for more papers by this authorZhi-Gang Tan
Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, 410011 Hunan Province, China
Search for more papers by this authorCorresponding Author
Jun Xiang
Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, 410011 Hunan Province, China
Correspondence: Jun Xiang Department of Neurosurgery, The Second Xiangya Hospital of Central South University, No. 139 Renmin Road, Changsha 410011, Hunan Province, China <[email protected]>Search for more papers by this authorFang Wen
Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, 410011 Hunan Province, China
Search for more papers by this authorZhi-Gang Tan
Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, 410011 Hunan Province, China
Search for more papers by this authorCorresponding Author
Jun Xiang
Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, 410011 Hunan Province, China
Correspondence: Jun Xiang Department of Neurosurgery, The Second Xiangya Hospital of Central South University, No. 139 Renmin Road, Changsha 410011, Hunan Province, China <[email protected]>Search for more papers by this authorAbstract
Objective. Copper-zinc superoxide dismutase (Cu-Zn SOD) is downregulated in epilepsy, however, the role of Cu-Zn SOD in epilepsy remains unclear.
Methods. Based on the pilocarpine hydrochloride-induced rat model of epilepsy, cortical-striatum brain slices of rats were examined based on field excitatory post-synaptic potentials. Pathological changes were observed by transmission electron microscope. Also using SH-SY5Y cells, flow cytometry and TUNEL staining were applied to investigate cell apoptosis, and ELISA was applied to detect SOD activity. In addition, qRT-PCR and western blot were performed to detect SCN2A/Nrf2/HO-1 gene and protein expression levels, respectively.
Results. Cu-Zn SOD over-expression suppressed epilepsy in vivo. In addition, Cu-Zn SOD knockdown notably decreased SOD activity and induced apoptosis in SH-SY5Y cells. Moreover, Cu-Zn SOD silencing decreased the levels of SCN2A, Nrf2 and HO-1. Lastly, Cu-Zn SOD was shown to modulate the NaV1.2/Nrf2/HO-1 axis in rats.
Significance. In this model, Cu-Zn SOD attenuated epilepsy and was shown to alter the expression level of proteins of the NaV1.2 /Nrf2/HO-1 signalling pathway, indicating that Cu-Zn SOD might be a target for the treatment of epilepsy.
Supporting Information
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