Phosphorylation of PRAS40 contributes to the activation of the PI3K/AKT/mTOR signaling pathway and the inhibition of autophagy following status epilepticus in rats
| Autor: | Junyi Lin, Keming Zhu, Liliang Li, Xiang Wang, Meng He, Aimin Xue, Yiwen Shen, You-Xin Fang, Beixu Li, Mingchang Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
autophagy Cancer Research Status epilepticus phosphorylated-PRAS40 03 medical and health sciences 0302 clinical medicine Immunology and Microbiology (miscellaneous) Western blot medicine Protein kinase B SE PI3K/AKT/mTOR pathway medicine.diagnostic_test Chemistry Autophagy Articles General Medicine Cell cycle mTOR pathway 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Cancer research Phosphorylation medicine.symptom |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-1015 1792-0981 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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