Imipramine enhances neuroprotective effect of PEP-1-Catalase against ischemic neuronal damage.
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.
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Korea.
Dae Won
DW
Kim
Duk-Soo
DS
Kim
Mi Jin
MJ
Kim
Soon Won
SW
Kwon
Eun Hee
EH
Ahn
Hoon Jae
HJ
Jeong
Eun Jeong
EJ
Sohn
Suman
S
Dutta
Soon Sung
SS
Lim
Sung-Woo
SW
Cho
Kil Soo
KS
Lee
Jinseu
J
Park
Won Sik
WS
Eum
Hyun Sook
HS
Hwang
Soo Young
SY
Choi
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D002374:Catalase / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005849:Gerbillinae; D007099:Imipramine / Q000494:pharmacology / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010455:Peptides / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D014161:Transduction, Genetic
D000929:Antidepressive Agents, Tricyclic; D018696:Neuroprotective Agents; C503924:Pep-1 peptide; D010455:Peptides; D011993:Recombinant Fusion Proteins; D003543:Cysteamine; D002374:Catalase; D007099:Imipramine