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Fenobam promoted the neuroprotective effect of PEP-1-FK506BP following oxidative stress by increasing its transduction efficiency
Authors:Eun Hee Ahn  Dae Won Kim  Min Jea Shin  Hyo Sang Jo  Seon Ae Eom  Duk-Soo Kim  Eun Young Park  Jong Hoon Park  Sung-Woo Cho  Jinseu Park  Won Sik Eum  Ora Son  Hyun Sook Hwang  Soo Young Choi
Institution:1.Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea;2.Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan 330-090, Korea;3.Department of Biological Sciences, Sookmyung Women’s University, Seoul 140-742, Korea;4.Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea
Abstract:We examined the ways in which fenobam could promote not only the transduction of PEP-1-FK506BP into cells and tissues but also the neuroprotective effect of PEP-1-FK506BP against ischemic damage. Fenobam strongly enhanced the protective effect of PEP-1-FK506BP against H2O2-induced toxicity and DNA fragmentation in C6 cells. In addition, combinational treatment of fenobam with PEP-1-FK506BP significantly inhibited the activation of Akt and MAPK induced by H2O2, compared to treatment with PEP-1-FK506BP alone. Interestingly, our results showed that fenobam significantly increased the transduction of PEP-1-FK506BP into both C6 cells and the hippocampus of gerbil brains. Subsequently, a transient ischemic gerbil model study demonstrated that fenobam pretreatment led to the increased neuroprotection of PEP-1-FK506BP in the CA1 region of the hippocampus. Therefore, these results suggest that fenobam can be a useful agent to enhance the transduction of therapeutic PEP-1-fusion proteins into cells and tissues, thereby promoting their neuroprotective effects. BMB Reports 2013; 46(11): 561-566]
Keywords:Fenobam  Ischemic damage  Neuroprotection  PEP-1-FK506BP  Protein transduction domains
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