Imipramine enhances neuroprotective effect of PEP-1-Catalase against ischemic neuronal damage |
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Authors: | Kim Dae Won Kim Duk-Soo Kim Mi Jin Kwon Soon Won Ahn Eun Hee Jeong Hoon Jae Sohn Eun Jeong Dutta Suman Lim Soon Sung Cho Sung-Woo Lee Kil Soo Park Jinseu Eum Won Sik Hwang Hyun Sook Choi Soo Young |
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Affiliation: | Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Korea. |
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Abstract: | The protein transduction domains have been reported to have potential to deliver the exogenous molecules, including proteins, to living cells. However, poor transduction of proteins limits therapeutic application. In this study, we examined whether imipramine could stimulate the transduction efficiency of PEP-1 fused proteins into astrocytes. PEP-1-catalase (PEP-1- CAT) was transduced into astrocytes in a time- and dose-dependent manner, reducing cellular toxicity induced by H(2)O(2). Additionally, the group of PEP-1-CAT (+) imipramine showed enhancement of transduction efficiency and therefore increased cellular viability than that of PEP-1-CAT alone. In the gerbil ischemia models, PEP-1-CAT displayed significant neuroprotection in the CA1 region of the hippocampus. Interestingly, PEP-1-CAT (+) imipramine prevented neuronal cell death and lipid peroxidation more markedly than PEP-1-CAT alone. Therefore, our results suggest that imipramine can be used as a drug to enhance the transduction of PEP-1 fusion proteins to cells or animals and their efficacies against various disorders. |
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