Fenobam promoted the neuroprotective effect of PEP-1-FK506BP following oxidative stress by increasing its transduction efficiency

Abstract

We examined the ways in which fenobam could promote not onlythe transduction of PEP-1-FK506BP into cells and tissues but alsothe neuroprotective effect of PEP-1-FK506BP against ischemicdamage. Fenobam strongly enhanced the protective effect ofPEP-1-FK506BP against H2O2-induced toxicity and DNAfragmentation in C6 cells. In addition, combinational treatment offenobam with PEP-1-FK506BP significantly inhibited the activationof Akt and MAPK induced by H2O2, compared to treatment withPEP-1-FK506BP alone. Interestingly, our results showed thatfenobam significantly increased the transduction of PEP-1-FK506BPinto both C6 cells and the hippocampus of gerbil brains.Subsequently, a transient ischemic gerbil model studydemonstrated that fenobam pretreatment led to the increasedneuroprotection of PEP-1-FK506BP in the CA1 region of thehippocampus. Therefore, these results suggest that fenobam can bea useful agent to enhance the transduction of therapeuticPEP-1-fusion proteins into cells and tissues, thereby promoting theirneuroprotective effects. [BMB Reports 2013; 46(11): 561-566]

Keywords

• Fenobam
• Ischemic damage
• Neuroprotection
• PEP-1-FK506BP
• Protein transduction domains