Protective effects of transduced PEP-1-Frataxin protein on oxidative stress-induced neuronal cell death.
Reactive oxygen species (ROS) actively contribute to the development of a number of human diseases including ischemia. In response to oxidative stress, frataxin has a significant ability to improve cell survival though its biological function is unclear in relation to ischemia. To explore frataxin's role in protecting against ischemic cell death, we constructed PEP-1-Frataxin cell-permeable fusion protein. In a dose- and time-dependent manner PEP-1-Frataxin rapidly transduced into astrocyte cells and protected them against oxidative stress-induced cell death. Further, using an animal model, immunohistochemical analysis revealed that PEP-1-Frataxin prevented neuronal cell death in the CA1 region of the hippocampus induced by transient forebrain ischemia. These results demonstrate that transduced PEP-1-Frataxin protects against cell death in vitro and in vivo, suggesting that transduction of PEP-1-Frataxin could be useful as a therapeutic agent for various human diseases related to oxidative stress.
Kim
Mi Jin
MJ
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
Kim
Dae Won
DW
Yoo
Ki-Yeon
KY
Sohn
Eun Jeong
EJ
Jeong
Hoon Jae
HJ
Kang
Hye Won
HW
Shin
Min Jea
MJ
Ahn
Eun Hee
EH
An
Jae Jin
JJ
Kwon
Soon Won
SW
Kim
Young Nam
YN
Won
Moo Ho
MH
Cho
Sung-Woo
SW
Park
Jinseu
J
Eum
Won Sik
WS
Choi
Soo Young
SY
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004396:Coloring Agents; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors; D005849:Gerbillinae; D006801:Humans; D033862:Iron-Binding Proteins / Q000096:biosynthesis / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000473:pathology; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles; D014161:Transduction, Genetic; D000096923:Frataxin
D004396:Coloring Agents; D003543:Cysteamine; D033862:Iron-Binding Proteins; D018696:Neuroprotective Agents; D010455:Peptides; D011993:Recombinant Fusion Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D000096923:Frataxin; C503924:Pep-1 peptide; C022616:thiazolyl blue