Transduced human copper chaperone for Cu,Zn-SOD (PEP-1-CCS) protects against neuronal cell death.
Reactive oxygen species (ROS) contribute to the development of various human diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS. SOD activity is dependent upon bound copper ions supplied by its partner metallochaperone protein, copper chaperone for SOD (CCS). In the present study, we investigated the protective effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1-CCS was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Moreover, transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells. Immunohistochemical analysis revealed that it prevented neuronal cell death in the hippocampus in response to transient forebrain ischemia. These results suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS provides a potential strategy for therapeutic delivery in various human diseases including stroke related to SOD or ROS.
Choi
Soo Hyun
SH
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
Kim
Dae Won
DW
Kim
So Young
SY
An
Jae Jin
JJ
Lee
Sun Hwa
SH
Choi
Hee Soon
HS
Sohn
Eun Jung
EJ
Hwang
Seok-Il
SI
Won
Moo Ho
MH
Kang
Tae-Cheon
TC
Kwon
Hyung Joo
HJ
Kang
Jung Hoon
JH
Cho
Sung-Woo
SW
Park
Jinseu
J
Eum
Won Sik
WS
Choi
Soo Young
SY
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002545:Brain Ischemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D003300:Copper / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D018832:Molecular Chaperones / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010269:Paraquat / Q000633:toxicity; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000627:therapeutic use; D014162:Transfection
C114678:CCS protein, human; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D003300:Copper; D010269:Paraquat