Transduced human PEP-1-catalase fusion protein attenuates ischemic neuronal damage.
Antioxidant enzymes are considered to have beneficial effects against various diseases mediated by reactive oxygen species (ROS). Ischemia is characterized by both oxidative stress and changes in the antioxidant defense system. Catalase (CAT) and superoxide dismutase (SOD) are major antioxidant enzymes by which cells counteract the deleterious effects of ROS. To investigate the protective effects of CAT, we constructed PEP-1-CAT cell-permeative expression vectors. When PEP-1-CAT fusion proteins were added to the culture medium of neuronal cells, they rapidly entered the cells and protected them against oxidative stress-induced neuronal cell death. Immunohistochemical analysis revealed that PEP-1-CAT prevented neuronal cell death in the hippocampus induced by transient forebrain ischemia. Moreover, we showed that the protective effect of PEP-1-CAT was observed in neuronal cells treated with PEP-1-SOD. Therefore, we suggest that transduced PEP-1-CAT and PEP-1-SOD fusion proteins could be useful as therapeutic agents for various human diseases related to oxidative stress, including stroke.
Kim
Dae Won
DW
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, College of Medicine, Hallym University, Chunchon 200-702, Korea.
Jeong
Hoon Jae
HJ
Kang
Hye Won
HW
Shin
Min Jea
MJ
Sohn
Eun Jeong
EJ
Kim
Mi Jin
MJ
Ahn
Eun Hee
EH
An
Jae Jin
JJ
Jang
Sang Ho
SH
Yoo
Ki-Yeon
KY
Won
Moo Ho
MH
Kang
Tae-Cheon
TC
Hwang
In Koo
IK
Kwon
Oh-Shin
OS
Cho
Sung-Woo
SW
Park
Jinseu
J
Eum
Won Sik
WS
Choi
Soo Young
SY
D002374:Catalase / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress; D010455:Peptides / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction
C503924:Pep-1 peptide; D010455:Peptides; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D003543:Cysteamine; D002374:Catalase; C558128:PEP-1-catalase fusion protein