期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 97, 期 -, 页码 250-262出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2016.06.009
关键词
Brain ischemia; Tat-PRAS40; Oxidative stress; Cell death; Protein therapy
资金
- Priority Research Centers Program through the National Research Foundation of Korea - Ministry of Education [NRF-2009-0093812]
- Ministry of Science, ICT & Future Planning in the Republic Korea
- Hallym University Research Fund [HRF-2015-05-008]
- BioGreen21 Program of the Rural Development Administration [PJ01121401]
Proline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and is known to play an important role against reactive oxygen species-induced cell death. However, the precise function of PRAS40 in ischemia remains unclear. Thus, we investigated whether Tat-PRAS40, a cell-permeable fusion protein, has a protective function against oxidative stress-induced hippocampal neuronal (HT-22) cell death in an animal model of ischemia. We showed that Tat-PRAS40 transduced into HT-22 cells, and significantly protected against cell death by reducing the levels of H2O2 and derived reactive species, and DNA fragmentation as well as via the regulation of Bcl-2, Bax, and caspase 3 expression levels in H2O2 treated cells. Also, we showed that transduced Tat-PARS40 protein markedly increased phosphorylated RRAS40 expression levels and 14-3-3 sigma complex via the Akt signaling pathway. In an animal ischemia model, Tat-PRAS40 effectively transduced into the hippocampus in animal brain and significantly protected against neuronal cell death in the CAl region. We showed that Tat-PRAS40 protein effectively transduced into hippocampal neuronal cells and markedly protected against neuronal cell damage. Therefore, we suggest that Tat-PRAS40 protein may be used as a therapeutic protein for ischemia and oxidative stress-induced brain disorders. (C) 2016 Elsevier Inc. All rights reserved.
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