title: 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 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.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea sychoi@hallym.ac.kr.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Ahn
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Min Jea
authors.initials: MJ
authors.lastname: Shin
authors.forename: Hyo Sang
authors.initials: HS
authors.lastname: Jo
authors.forename: Seon Ae
authors.initials: SA
authors.lastname: Eom
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Park
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Park
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.forename: Ora
authors.initials: O
authors.lastname: Son
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Hwang
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000494:pharmacology / Q000627:therapeutic use; D022021:Tacrolimus Binding Proteins / Q000096:biosynthesis / Q000494:pharmacology* / Q000627:therapeutic use; D014161:Transduction, Genetic
chemical_list: D007093:Imidazoles; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; C032794:fenobam; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D022021:Tacrolimus Binding Proteins