Tat-PRAS40 prevent hippocampal HT-22 cell death and oxidative stress induced animal brain ischemic insults.
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 14-3-3σ 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 CA1 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.
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea.
Min Jea
MJ
Shin
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea.
Dae Won
DW
Kim
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea.
Hyo Sang
HS
Jo
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea.
Su Bin
SB
Cho
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea.
Jung Hwan
JH
Park
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea.
Chi Hern
CH
Lee
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea.
Eun Ji
EJ
Yeo
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea.
Yeon Joo
YJ
Choi
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea; Bioceltran Co., Ltd., Chuncheon 24234, Republic of Korea.
Ji An
JA
Kim
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea; Bioceltran Co., Ltd., Chuncheon 24234, Republic of Korea.
Jung Soon
JS
Hwang
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea.
Eun Jeong
EJ
Sohn
Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31538, Republic of Korea.
Ji-Heon
JH
Jeong
Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31538, Republic of Korea.
Duk-Soo
DS
Kim
Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Hyeok Yil
HY
Kwon
Department of Neurosurgery, Hallym University Medical Center, Chuncheon 24253, Republic of Korea.
Yong-Jun
YJ
Cho
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea.
Keunwook
K
Lee
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea.
Kyu Hyung
KH
Han
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea.
Jinseu
J
Park
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. Electronic address: wseum@hallym.ac.kr.
Won Sik
WS
Eum
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. Electronic address: sychoi@hallym.ac.kr.
Soo Young
SY
Choi
D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000473:pathology; D002460:Cell Line; D053938:DNA Fragmentation; D004353:Drug Evaluation, Preclinical; D005849:Gerbillinae; D008297:Male; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
D048948:14-3-3 Proteins; D051017:Apoptosis Regulatory Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; C508191:proline-rich Akt substrate, 40 kDa protein, mouse
Brain ischemia; Cell death; Oxidative stress; Protein therapy; Tat-PRAS40