Phosphorylation of PRAS40 contributes to the activation of the PI3K/AKT/mTOR signaling pathway and the inhibition of autophagy following status epilepticus in rats

Junyi Lin; Youxin Fang; Mingchang Zhang; Xiang Wang; Liliang Li; Meng He; Aimin Xue; Keming Zhu; Yiwen Shen; Beixu Li

doi:10.3892/etm.2020.9085

Phosphorylation of PRAS40 contributes to the activation of the PI3K/AKT/mTOR signaling pathway and the inhibition of autophagy following status epilepticus in rats

Exp Ther Med. 2020 Oct;20(4):3625-3632. doi: 10.3892/etm.2020.9085. Epub 2020 Jul 31.

Authors

Junyi Lin^{1

2}, Youxin Fang³, Mingchang Zhang², Xiang Wang⁴, Liliang Li², Meng He², Aimin Xue², Keming Zhu⁵, Yiwen Shen², Beixu Li^{1

2}

Affiliations

¹ School of Policing Studies, Shanghai University of Political Science and Law, Shanghai 201701, P.R. China.
² Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China.
³ General Family Medicine Clinic, Xuhui District Xietu Subdistrict Community Healthcare Center, Shanghai 200120, P.R. China.
⁴ Institute of Forensic Science, Jiading Branch of Shanghai Public Security Bureau, Shanghai 201800, P.R. China.
⁵ Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China.

Abstract

Status epilepticus (SE) is a neurological disorder associated with high morbidity and mortality rates, and is often difficult to treat. Moreover, the underlying mechanism of SE remains unknown. The lithium-pilocarpine model is a validated animal model that can reproduce the main clinical and neuropathological features of SE. In the present study, this SE model was utilized and SE was successfully established in rats, as determined by the corresponding epileptic electroencephalogram. Histology, immunohistochemistry, western blot analysis and co-immunoprecipitation were used to detect the phosphorylation (p-) of AKT substrate of 40 kDa (PRAS40), the combination of p-PRAS40 and 14-3-3 protein and the activation of the PI3K/mTOR signaling pathway in SE. In addition, the present study analyzed the dynamics of the expression of autophagy-associated factors in the hippocampus after SE induction, and the influence of suppressing the p- of PRAS40 on the autophagy process was detected in the pathogenesis of SE. The results indicated that increased p-PRAS40 expression could activate the mTOR pathway to decrease the level of autophagy. However, inhibition of the mTOR signaling pathway promoted autophagy flux. These results may provide further understanding of p-PRAS40 functions in SE.

Keywords: SE; autophagy; mTOR pathway; phosphorylated-PRAS40.