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KMID : 0624620130460110561
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BMB Reports
2013 Volume.46 No. 11 p.561 ~ p.566
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Fenobam promoted the neuroprotective effect of PEP-1-FK506BP following oxidative stress by increasing its transduction efficiency
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Ahn Eun-Hee
Kim Dae-Won
Shin Min-Jea
Jo Hyo-Sang
Eom Seon-Ae
Kim Duk-Soo
Park Eun-Young
Park Jong-Hoon
Cho Sung-Woo
Park Jin-Seu
Eum Won-Sik
Son O-Ra
Hwang Hyun-Sook
Choi Soo-Young
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Abstract
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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.
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KEYWORD
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Fenobam, Ischemic damage, Neuroprotection, PEP-1-FK506BP, Protein transduction domains
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