Transduced human PEP-1-heat shock protein 27 efficiently protects against brain ischemic insult.
Reactive oxygen species contribute to the development of various human diseases. Ischemia is characterized by both significant oxidative stress and characteristic changes in the antioxidant defense mechanism. Heat shock protein 27 (HSP27) has a potent ability to increase cell survival in response to oxidative stress. In the present study, we have investigated the protective effects of PEP-1-HSP27 against cell death and ischemic insults. When PEP-1-HSP27 fusion protein was added to the culture medium of astrocyte and primary neuronal cells, it rapidly entered the cells and protected them against cell death induced by oxidative stress. Immunohistochemical analysis revealed that, when PEP-1-HSP27 fusion protein was intraperitoneally injected into gerbils, it prevented neuronal cell death in the CA1 region of the hippocampus in response to transient forebrain ischemia. Our results demonstrate that transduced PEP-1-HSP27 protects against cell death in vitro and in vivo, and suggest that transduction of PEP-1-HSP27 fusion protein provides a potential strategy for therapeutic delivery in various human diseases in which reactive oxygen species are implicated, including stroke.
An
Jae J
JJ
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon, Korea.
Lee
Yeom P
YP
Kim
So Y
SY
Lee
Sun H
SH
Lee
Min J
MJ
Jeong
Min S
MS
Kim
Dae W
DW
Jang
Sang H
SH
Yoo
Ki-Yeon
KY
Won
Moo H
MH
Kang
Tae-Cheon
TC
Kwon
Oh-Shin
OS
Cho
Sung-Woo
SW
Lee
Kil S
KS
Park
Jinseu
J
Eum
Won S
WS
Choi
Soo Y
SY
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D020520:Brain Infarction / Q000517:prevention & control*; D016923:Cell Death; D002470:Cell Survival; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005822:Genetic Vectors / Q000235:genetics; D005849:Gerbillinae; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus; D006801:Humans; D015227:Lipid Peroxidation; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects; D018384:Oxidative Stress; D010455:Peptides / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D014161:Transduction, Genetic
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C503924:Pep-1 peptide; D010455:Peptides; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D003543:Cysteamine